Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
1065;~74
This invention pertains to a method of exciting a
chemical species to achieve mobility for orientating, reposi-
tioning and transporting the species and for separation among
species achieved by operation at the appropriate conductivity
range of the media-and especially within the semiconductive
range when induced by means of intense electrical fields at or
near minimum and optimum current levels. Such systems are
- characterized by extremely fast molecular motion, or transport,
hereinafter called electromolecular propulsion (E~), as well
as by great differentiation or resolution of molecular species.
Such resolution is capable of accomplishing very refined
analytical separations.
- The present invention, in one broad aspect, resides
in a process which comprises imparting mobility to a chemical
species by providing a semiconductive transport medium and
impressing a voltage of about 0.05 to 25,000 volts/cm across
the medium sufficiently high to produce a current density in
the range of about 0.001 to 400 microamps/cm2 and equal to or
exceeding the threshold current value for the species in the
medium, below which value the species remains substantially
stationary, to induce a high mobility rate for the species.
In another broad aspect, this invention resides in
a process which comprises imparting mobility to a biochemical
species by providing a fluid semi-conductive medium comprising
water, a conductivity suppressant, a high dielectric constant
component, and a component selected from the group consisting
of mobilizers and initiators, and applying a voltage within
the range of about 0~05 to 25,000 volts/cm across the medium
sufficiently h gh to produce a current density of at least
2 microamps/cm and equal to or exceeding the threshold current
., .
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~` 1065Z74
value for the biochemical species in the medium, below which
value the biochemical speciss remains substantial'y stationary.
Also provided by this invention is a process for
effecting conduction in a gas which comprises providing a
multi-component gaseous semi-conductive medium containing
components with proton donor/acceptor interaction capability,
,...
, high dielectric constant and high conductivity and applying
i a voltage of about .05 to 30,000 volts/cm to achie~e continuous
conduction.
A yet further aspect of the present in~ention is the
method of separating a mixture of substantially non-polar dyes
which comprises mixing said dyes with a semi-conductive medium
on a substrate and applying a voltage in the range of from 200 to
25,000 volts/om at a current density in the range of about 0.001
to 400 microamp/cm across said substrate, said current density
being equal to or exceeding the threshold current level for one
dye but below the threshold for at least one other dye in said
mlxture.
By comparison with conventional techniques, hereto-
fore unobtainable or unique mobilities as well as system versa-
tility can ke achieved. This invention provides a method for
inducing mobility of molecules previously considered non-mObile
due to their non-polar nature. In the case of polar molecules,
such as certain metal derivatives, a greater resolution is
obtained than that achieved with conventional conductive or
aqueous eiectrolytes. These, plus additional useful factors
favoring this technique, permit exceedingly high resolution
separation or purification of different types of molecular
species to be efficiently and very rapidly achieved. Suitable
detection and/or separation means gives this process an import-
ant utility for analytical, purification, and production
:. .
proce2ures. It also serves as a research tool for the study,
characterization and elucidation of structural and physical-
chemical attributes of chemical systems, materials
- 2 -
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-' 106527~
and their interactions.
An aspect of this invention pertains to the prepara-
tion of suitable media and systems, within which the semicon-
ductive molecular transport can be reliably accomplished. This
S can be performed in various media; i~ being generally convenient
to utilize liquids for the mobile phase. The conductivity of
the entire system or process is brought within the semiconductive
range by adjusting the conductivity level of the media constitut-
ing the mobile phase. Very high voltages may be sustained at low
current levels such that the thermoelectric heat buildup (I2RT)
nevertheless permits usage of readily available materials and
techniques for working systems. In contrast to conventional
electrochemical transpoxt methods, in this invention very minute
current levels are actually required which correspond to the
semiconductive nature of the process. This often precludes the
need for employing external heat convective means and permits
small working configurations and small power supply size require-
ments. Another advantage of the process is that at the low heat
levels of this invention thermal interference is minimized. The
very low current levels which suffice in this invention are near
optimum for molecular movement as induced by the attractive-
repulsive interaction within the electricfield, and, under such
condition~, a very intense migratory effect can be induced which
is proportional to the voltage potential applied. This migratory
effect is characteristic for the molecular nature of the material
and may be sharply differentiated from even similarly or related,
though unidentically structured, molecules. The characteristic
mobility of a substance in cm/sec may be used to classify or
identify substances. The great degree of molecular resolution
or differentiation may be accomplished over the distance of a
11)~;5Z74
few inches in a matter of seconds or minutes wherein proportion-
ately less time i~ required over small distances or by the use
- of higher voltages. I have discovered that certain low current
levels are near optimum for the EMP process and are defined
herein as threshold level function dependent upon the molecular
nature of the materials involved. The threshold refers to
excitation level states in a solvation-adsorption system. The
usual observed ranges are 2xlO 7 to 1.6x10-5 amp/cm2 for a
cellulose substrate. Such threshold levels refer to minimal
current requirements for initiating the EMP process and are
usually close to the optimum current requirements for a given
system. The semiconductive range refers to method~ to achieve
suitable conductivity at high voltage at the threshold range.
The media used are capable of sustaining high voltage electrical
fields and are tailored to have a chemically adjusted and/or
controlled level of aonductivity internal to the mobile phase
and in combination with the substrate, by technique~ consistent
with the various electrical, chemical and operative requirements
of the working system.
Under such conditions an intense compulsive regponse
with very fast mobility or orientation and high resolution
separation of molecular types are readily achieved. Such systems
are very convenient and advantageous to operate. Their effi-
ciency is high; heat loss is a minimum, and they are applicable
within aqueous, hydrophobic and otherwise non-aqueous media.
This process may be accomplished as a liquid-state
semiconductive transport or gaseous state semiconductive trans-
port. Due to it~ ability to effect molecular transpositions
and its use of a mobile phase, it i8 a ~emiconductive fluidic
process~ This distinguishes it from the sessile solid state
4.
1065274
and amorphous semiconductive system~. By vi~tue of it~ effect
upon the electromolecular nature of materialR through induction
by and reaction to suitably intense electrical fields this
process has applications to major classes of known molecular
materials including inorganic ions, organic molecules, colloids,
and crystalloids. Thu6, this process i9 applicable to inorganlc
materials such as derived from iron, copper, nickel, cobalt,
rare earths, heavy metals, zirconium, and the separation of ionic-
solvate specie~ of metal derivatives. It is alao appl~cable to
other materials such a~ proteins, antiblo~ics, vitamins, anti-
histamine~, amino acido, dye~tuffs and blood eon~tituents.
By virtue of the ex~remely great resolution whieh can
be obtained by application of EMP and the very greAt speed with
; j~ which such s~parations can be achieved, and the various typeR of
oy~tems in which the process can be applied, it offero advantages
and applicatlon~ to various fields and operative procedures,
including: analytlcal chemistry, quallty control, ellnlcal
ehemistry~ renearch; preparative chemlstry~ physleal chemistry;
purifieationt extractionJ proce~ eontrolJ applled ehemi~try;
and semleonductlve technology.
By way of lllu~tratlon, ln preparatlvo choml_try, chemi-
cal reaction~ conducted under ~ultable EMP aondltlono oan be
uoed to dlaplaee roaetlon o~ulllbrla to ~avor ~rtaln ylelds.
It o~fer~ a meano for ooleetlve aeplotlon of e~ulll~rlum produet
from the ~phere of the roaetlon zone, or of eontaminants, or
byprodueto. In oxtraetlon, EMP aet~ ao a mlnlmal tlme eon~umlng
proee~o eopsolally ~rom thln-walled matorlals, partleulate~, or
; porou~ ~ubotanees. In applled ehomiatry, it lo u~ful whore very
rapid ana/or ~eloetlve ponetratlvo proee~ing ia d~lrad, e.g.,
ln dyoing or de~talnlng fabrle~. The dyoa or oth~r d~toetable
~065~74
- molecules in a mixture may be individually deposited in a pre-
selected or ordered pattern by control of their EMP response.
Another advantage of the invention is that it permits
the separation, characterization, or study of molecular types
` S by virtue of the differential threshold levels. It permits
~ control at different levels under various conditions of pH,
- temperatures, different media, or other internal or external
factors. An application of this would be a process which is con-
; trollable by first operating the system at the lower threshold `
level to effect the first separation; then going on to subsequent
~`- levels in order to complete the resolution.
Major operative features for the practice of the
invention are:
1. Adjusting the operative phase to the s~miconductive
range to provide operation at or near molecular threshold levels
and maximum or convenient voltage levels capable of being
` sustained by the system.
2. Establishing the optimum current level at or near
the molecular threshold level at the given voltage for effective
molecular resolution.
3. Utilizing those components within the system and
arranging the systèm characteristics such that overall stability,
reproducibility, and safety, are attained.
A useful analogy of this phenomenon and its relationship
to electrochemistry is the comparison of solid state semiconduc-
tive physics with its earlier thermionic electrical technology.
Some similarities may be noted from the following characteristics
of the EMP process.
1. Power supply wattage (and size) requirements are
minimized.
, . .
:
A 6.
.
. ~
:
l~ `
.~
1~)6S274
2. Minimal electrothermal losses permit small working
dimensions and increased field intensities; this contributes to
fast re~o~ution times at low distortion levels.
3. The deteriorating influence upon the system as a
result of brute force power requirements, and its attendant
heat effects, is eliminated. For example, at higher current
densities than those used in this invention the mobility and
resolution character of molecular species may be altered.
.!.,' 4. The degree and manner of the electrical utilization
is not restricted to the more conventional conductivity modes,
such as aqueous electrolyte ion transport in liquid phase.
Therefore, vast numbers of different types of materials may be
acted upon, studied, or utilized in the EMP process. This
includes materials and systems whose electrical or ionic contri-
bution would be t~ou~htmeager from anticipation of theix molecularstructures. Additionally, a broad range of nonaqueous, hydrophobic,
and otherwise nonpolar substances as well as ionic, polar,
covalent, aprotic, or other types of conductive substances may
be included. This semiconductive fluidic process thereby serves
as a new and convenient tool to explore various aspects within
these fields, some of which are relatively unknown; as well as
to elucidate molecular structure, excitation states, electro-
molecular interaction and nature of materials.
5. Operation at or near the low threshold levels
can be achieved with an overall high electrical propulsive
efficiency. These thre9holds are characteristic for a material
and generally exist at very low power levels. This then defines
an operational propulsive efficiency whereby this process is
capable of use at power levels just sufficient to effect the
molecular specieg' propulsion, and wherein the electrothermal
7.
. , .
- 1C)65Z~
losses approach negligible values. Actually, thermal increments
become negligible at very low power levels, especially in a low
`, efficiency electrothermal system. Counteracting factors include
evaporative cooling, reservoir heat capacity, thermal convection,
' 5 and in certain situations dissipation by convective factors
such as electroendosmotic streaming. By the controlled operation
at increasing threshold levels the molecular species in turn will
be induced into propulsion at their appropriate and characteristic
level irrespective of other materials which may be present. This
provides an additional high resolution technique which is capable
of differential molecular discrimination. This discriminatory
process is further enhanced by virtue of the propulsion rate
also being characteristic for the molecular species involved.
This migratory or propulsive rate can be caused to vary substan-
tially by modification of the media.
Appropriate to the mechanism of propulsion threshold
, ~ it is noted that this behavior determines that point where the
molecular attraction or adhesion to the substrate (surface) is
counteracted by the total energy input. ~his is comprised of
the external electrical energy input plus what other distribu-
tion is due to additional partition functions present. The
~, molecules are then free to migrate or be swept by electrical
: attraction or othqr convective factors. The electrical charac-
teristics of the systems show a nonlinearity a~ the current will
!:, 25 gradually rise after the initial application of a given voltage.
The preferred systems rapidly stabilize and remain in electrical
equilibrium during the separatory process, although the process
r,' may be carried out as gradual changes occur in the electrical
characteristics. In cases where a lack of stability causes
i; 30 difficulty but the medium is otherwise considered useful, the
: .
8.
1065Z74
rate of change in resistance of the system may be reduced by the
addition of an external resistance of sufficient magnitude, for
example, about equal to or greater than the magnitude of the
internal resistance of the system. Alternatively, an active
electrical element may be utilized which is capable of sensing
the current-voltage or temperature levels within a system and
serve to regulate these faGtors or changes therein by means of
control of the power source. This procedure is also of value as a
.
safety feature. --
,: ...
Investigation of components for media formulation has
shown that certain compound combinations are not feasible for use
in EMP if stable current levels are desired. When a constant ~-
voltage is applied, these combinations continually exhibit a
different resistance as if a capacitor were being charged. This
effect may be illustrated in the form of a plot of current
against time at constant voltage, where tl and t2 are on the
order of several seconds or minutes:
GRAPH II
A
~ B
Current ~
.. ~ C
tl t -- - Time
A material or mixture with electrical characteristics
20 of type A (continually increasing current) may eventually suffer
arcing over. A material or mixture of type C (increasing cur-
- rent, and then decreasing current after a point) is subject to
evaporative heating and so eventually burns, chars or dries out.
A material or mixture of type B is a preferable medium from the
point of view of electrical control because it allows reproduci-
bility of runs and readjustment of the electrical characteris-
-- g _
.
:
. . :, , - , . . -, , ~. : .
, ' ' : . : ~ - ' - ~ - :'
- ~
` 10~527~
tics is not a concern. Materials exhibiting electical behavior
of type A may be deliberately chosen as media components to off-
set the properties of a medium which otherwise exhibits type C
behavior, and vice versa. Also, the electrical characteristics
of a given compound may change depending on the other substances
with which it is mixed. Examples of compounds illustrating type
A behavior in some mixtures and type B behavior in others is
given below. Generally one would choose a media component which
exhibits type B behavior in conjunction with the other components
in the system.
COMPOUNDS TYPE BEHAVIOR
:
N,N-dimethylacetamide in water A
N,N-dimethylacetamide in formamide A
N,N-dimethylformamide in water B
~' 1,2-propanediolcyclic carbonate in water A
ethylene carbonate in water B
3-methyl sulfolane in water A
2-pyrrolidinone in water A
N-methylformamide in water A
N-methylacetamide in water B
tetrahydrofurfuryl alcohol in water B
tetrahydrothiophene dioxide in formamide A
diacetone alcohol in formamide A
diacetone alcohol in thiodiethylene glycol B
"Cellosolve"* in formamide A
"Cellosolve" in thiodiethylene glycol B
The EMP process differs from the prior art processes
of electrophoresis and dielectrophoresis in a number of respects,
EMP exhibits non-linear electrical characteristics departing
from the Kohlrausch requirement for electrolytes and from Ohm's
Law.
- *Trademark for ethylene glycol monoethyl ether
''' `'' - 10 - ;
'.......................................................................... .
' :
. . - . : .
:
` 106~74
.,
Specifically, the following characteristics are observed with
EMP:
(1) non-doubling of current with doubling of voltage
(2) non-constant resistance with time
,
; 5 (3) non-constant resistance with voltage or current
Furthermore, the EMæ response does not seem to be
very affected by viscosity; and the EMP response iR enhanced by
increasing the dielectric constant of the solution while the
electrophoretic mobility is inversely proportional to dielectric
constant so EMP may be practiced at dielectric levels far
exceeding those practicable with electrophoresis. Thus EMP
in media with a dielectric constant up to 190 has been practical,
e.g., in N-methylacetamide.
The migration rate in cm/sec of chemical species
transported by EMP is markedly superior to the rates achieved
with dielectrophoresis and electrophoresis. This difference is
illustrated by the following graph:
- GRAPH I
'. ` \
~og of Migration
Rate ;~ Electrophor sis
ielectrophoresis s~emiconductive e~ectrolyte conduction
range
Conductivity
It is thought that the EMP process relies on proton
donor/acceptor interactions and electron charge transfer com-
;
plexes for transport. See R. Foster, Organ ~ ransfer
11 .
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1065274
Complexes (1969).
In practical terms, a key consideration in this processpertains to the use of a relatively nonconductive medium. Various
different media and techniques may be used to achieve the require-
ment~ of the semiconductive ranges employed. Conduction can becarried out in solids, semisolids, such as gels, as well as in
the gaseous phase, aerosols, foams and liquids. Also combina-
tions of these are practical as are melts, high temperature
melts, pseudo crystals (para crystals and mesomorphic materials),
ices, slushes, glasses, plastics, fibers, filaments, porous
- materials and powders. Ion exchange media, permaselective and
membrane barriers, dialytic membranes, molecular sieves and
specific ion source materials are suitable as supports or
barriers. The process may be carried out continuously or by
the batch technique.
Many substances are relatively dielectric; of these
- the nonpolar organics constitute a vast grouping. Some of these
exhibit intermediate ranges of conductivity or are susceptible
to appropriate adjustment of their conductive nature by addition
of relatively small amounts of adjuncts. This may be likened
to the process of doping or implantation used with solid-state
devices. Other means may include irradiation, polarization
interaction, injection or radioactive or charged particulates,
photo activation, superposition of AC fields, magnetic fields
or other energizing means. These energizing fields may be
oriented at different angles with respect to the DC field. For
example, an AC field superimposed upon the DC field used in this
invention may be used to impart additional mobility to chemical
species within a medium. Pulsed DC or the superimposition of
pulsed DC may also be u~ed. A relatively polar material can be
12.
~ 065~27~
used as the medium, such as aqueous solutions, by limiting the
ionic content of the system to achieve the desired conducti~ity
level. Also, suppressive substances can be add~d to a conductive
system, desirable materials being those which exert a suppressive
effect beyond the mere dilution effect which their presence
contributes to the system. ~urther, the suppressive effect of
nonpolar materials used in comixture with otherwise conducting
systems offers a ~ery general and useful approach to the control
of conductivity. It is important to note that in regard to all
of these techniques other factors may favor certain additional
properties and characteristics of the materials employed appro-
; priate for the nature of the application, such as miscibility,
compatibility, toxicity, boiling point, melting point, reactivity,
cost, removability, dialyzability and osmolality. A high
dielectric constant material is often preferred due to itsability to maintain the charges formed in the system (involving
solvation or interaction) or charges otherwise acquired or
- induced upon chemical species. The attainment of a controlled
level of conductivity may be further controlled or adjusted by
the simultaneous consideration of other system parameters, such
as pH, physical state and temperature.
Mixed solvents may be used with the intermediation of
a coupling agent, usually of a semipolar cosolvent nature. The
term semipolar is used for amaterial which shows some conduc-
tivity, which will increase upon dilution with water (or othersimilarly polar material), and which will increase upon addition
of a soluble ionic salt. Thus, in the present invention the
solvation of a strongly ionic material into a nonpolar one by
means of a semipolar material will generally produce only a
minor conductivity increase; whereas the solution of the ionic
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13.
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` ~06527~
material in the ~emipolar solvent alone may be moderately con-
ducting. In effect, the nonpolar material may b~ viewed as
- suppressing the capabilities for moderate conduction to form
a three-way system. The three-way system therefore comprises
; 5 an inert base, a conductivity agent and a semipolar material,
such as, respectively, xylene, ammonium bromide and dimethyl
formamide. Further, a considerable increase in the amount of
the semipolar solvent may only minimally improve the conductivity.
The addition of a relatively small volume of a second type of
semipolar solvent (a four-way system) can then effect a very
substantial conductivity increase of the entire system. Neither
. .
cosolvent alone with the nonpolar material, without or including
the solvated ionic material will approach the conductivity level
so achieved. This technique for augmenting the conductivity of
essentially nonpolar materials forms a convenient working basis for
the use of substances such as xylene, p-cymene, mineral oil
and chlorinated solvents. An illustration of a four-way system
is xylene, ammonium bromide, dimethyl acetamide and dimethyl
` formamide.
The above effects also may be applied to systems which
are not readily io~izable and the components determined by such
factors a~ dielectric constant and proton donor capability of
the sol~ating molecules. Whereas medium donor capability may
give rise to solvated molecules, a high donor capability in a
high dielectric system readily tends to preserve the ionic
. .
charges so created. Of particular use are media having dielectric
constants above 10, which tend to maintain charges formed by
proton donor acceptor exchange.
The media used in this invention are characterized by
` 30 liquidity at or near room temperature, and sufficiently high
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14.
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.
106527~ :
boiling points to withstand the process heat. The boiling
points are generally above 140C, and preferably above 165C.
The media need not be capable of dissolving the chemical to
which mobility is to be imparted, but solubility is preferable
for separation of different molecular species.
This invention is further illustrated by the following
examples directed to the separation of chemical species in the
indicated media. The apparatus consisted of a high density
polyethylene separation cell divided into two 15cc compartments.
These are separated by a space containing a support bridge for
a spanning support substrate.
The cell was constructed to withstand and provide
security from the high voltage fields and conductive leakage of
media under such fields and the wide range of strong and cor-
rosive solvent materials used herein. A platinum electrode in
each compartment was connected to a DC power source generally
- operated at 1.25 ma. The power source was capable of metered
operation at variable voltage levels in the ranges of 0-lOOJ~a,
.j~
0-1 ma, and 0-10 ma, for threshold studies and operation of the
processes described herein. A filter paper wick in each compart-
ment was connected to opposite ends of the filter paper substrate
which extended across the top of the cell. The filter paper was
five cm wide by ten cm long and except where stat~d otherwise it
was "Whatman"* #3. Normally, the voltage drop in this system
occurs substantially across the impregnated support, for example
from 70% to 90% or more. The cell was enclosed by a transparent
cover.
, A suitable solvent can be selected from the class of
low molecular weight glycols with a minor amount of an additive
to increase conductivity. The following solvent systems are
useful for relatively nonpolar dyestuffs as well as other
*Trademark - 15 -
1065Z74
soluble organic materials. The solvents listed were used for
the separation of mixed chemical species, such as dyes,
"Mercurochrome"*, and sodium riboflavin phosphate, at the voltage
and current shown. The term "stabilized" is used to indicate
that the electrical characteristics reached the indicated values
and remained constant for the few minutes (generally two to
ten minutes) during which the separation process was completed.
ELECTRICAL
CHARACT~RISTIC
EXAMPLE SOhVENT FORMULAE (Stabilized)
LD 1 0.3 ml. water, 0.2 ml. Sorensen
Buffer (pH 7.0), 24.5 ml. propyl-
ene glycol. The amount of water in
this type of sy~tem should preferably
- not exceed about 2~ ll KV/ma
2 2.0 ml. dimethyl acetamide, 1.0 ml.
phenol, 25.0 ml. propylene glycol. 8 KV~ma
` 3 2.5 ml. formamide, 22.5 ml. propylene
L5 glycol. 5.5 KV/ma
Example 3 is excellent for dye resolution of the
following mixture: safranine O, tol~ylene red (neutral red) and
sodium riboflavin phosphate. This medium is also useful for
separation of members of the rhodamine dyestuff family.
!0 Unlike conventional ionic-transport processes the
mobilization of metal derivatives is not readily achieved, even
when the metal derivatives are soluble in the media. However,
by adjustment of the media and electrical characteristics in
accordance with this invention a very fine resolution is
!5 obtained, which illustrates a new mode of operation as described
herein. By suitable modification of the above solvent systems,
metal ion movement may be made practical, as in the following
systems. Examples of suitable metal ions are Co++, Cu++,
Ni++ from ~alts, such as the chlorides and nitrates.
16.
* Trademark for the disodium salt of dibromohydroxymercury-
fluoresceine; it is used as an antiseptic.
- .. . . . .
. 1065274 ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized)
4 lO ml. dimethyl formamide, 15 ml.
propylene ~lycol 10 KV/ma
lO ml. dimethyl formamide, 15 ml.
propylene glycol, l ml. triethanola-
: mine 8 KV/ma
Another approach is to use dithizone derivatives of
metals such as cobalt, copper and nickel in solvent systems such
as (4) and (5) above.
An ester based nonaqueous system is also satisfactory
as illustrated below. In place of the "Cellosolve"* in the medium,
other related compounds can be used, such as hexyl "Cellosolve"l,
" 2 3 4
methyl Carbitol" , "Cellosolve" acetate , and "Carbitol" acetate .
i,. ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized)
6 4 ml. formamide, 14 ml. "Cellosolve",
34 ml. dimethyl phthalate15 KV/ma
The following examples show tailoring of the conductivity
levels (doping) via nonaqueous salt methods and especially the
additional influence of a second semipolar material wherein n-
butanol S is a saturated solution of ammonium bromide in n-
butanol. This medium is illustrative of a four-way system dis-
cussed above, and is useful for the separation of dyes and
other compounds soluble therein.
ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE(Stabilized)
.
7 5 ml. n-butanol S, 30.5 ml. n-
decanol, 2 ml. l-methyl-2-pyrrolidinone 14 KV/ma
The following solvent ~ystems are useful for separation
of metal ~ons and complexes; of the metal complexes, dithizones,
17.
* Trademark for a series of mono- and dialkyl ethers of ethylene
glycol and their derivatives. The term "Cellosolve" used alone
signifie~ ethylene glycol monoethyl ether.
1 Trademark for ethylene glycol monohexyl ether.
2 "Carbitol" is the trademark for a series of mono- and dialkyl
ethers of diethylene glycol and their derivatives. Methyl
"Carbitol" is diethylene glycol monomethyl ether.
3 Trademark for ethylene glycol monoethyl ether acetate.
4 Trademark for diethylene glycol monoethyl ether acetate.
. .~. . ~.
: ` ~065Z74
,. :
' nitroso ~ -naphthol, pyrocatechol violet, rhodamine B, 8-hydroxy
~, quinoline, and dibenzoylmethane der'ivatives were used.
i ELECTRICAL
CHARACTERISTI~
EXAMPLE SOLVENT FORMULAE (Stabilized)
8 30 ml. methoxy ethoxy ethanol + 30 ml.
1, 2-propanediol cyclic carbonate +
3 drops nitric acid (1:30 in H20) 6.4 KV/1.25 ma
~ ' Thè medium of Example 8 gave multizone resolution
,~ (5 minutes) with rare earth 8-hydroxy quinolinates such as Sc ~'~
and Eu as well as other metals such as Ni. The heavy metal ,,~
~ 10 derivatives of dibenzoylmethane and rhodamine showed good to
j', excellent movement whereas with heavy metal nitrates movement ,
.... .
, was very sparse and with hafnium (as chloride) not at all. ,~
.. . " .
, , Satisfactory mobility was also obtained for Co+2, Cu,+2, and
,,,, Ni+2 (as chlorides).
In the previous example the nickel chloride gave '~
three zones, with spot coloration of blue and violet. Such
'' reproducible effects demonstrate the very great resolution of '
,, the technique. This also points to the formation of a series
~ of metal complexes, such a~ by proton donor/acceptor exchange,
,,, 20 and the ability of the technique to differentiate and resolve
' them. This unusua,l capability is evidenced by another situation
,; where not only do multizones appear, but these appear as both
~+) or (-) moving entities. Mobility rates of +2 cm/min were
~'; achieved with the following systems.
ELECTRICAL
CHARACTERISTIC
. EXAMPLE SOLVENT FORMULAE (Stabilized?
,' 9 15 ml. methoxy ethoxy ethanol 6.8 XV/ma
+ 15 ml. 1,2-propanediol cyclic Cu+2 (chloride)
carbonate +6 ml. isophorone 3 zones (+ and -)
;' +3 drops nitric acid (1:30) Fe+3 (chloride)
5-6 zones (+ and -)
, Ni+2(chloride)
, 3 zones (-)
,, , 6 min. run
~' ~
,: :
. . .
:,~ . . .
.
i,~,,;~,~l 18.
, . ..
'. ,. .: . . ' ~ . ~ , ,
. . ~ . ,.
~065274
15 ml. methoxy ethoxy ethanol 6 KV/ma
+15 ml. 1,2-propanediol cyclic Co+2(chloride)
carbonate + 13 ml. ethylene 2-3 zones (+ and -)
carbonate +3 drops nitric acid Ni+2 (chloride)
30) 2-3 zones (+ and -)
Cu+2(chloride)
4-5 zones (+ and -)
6 min. run
The medium of Example 10 also provided excellent
; mobility for salts of europium, lutetium, thallium and ytterbium.
~- The positlon, mobility rate, and character of the zones o~tained
are characteristic for the material within the system under given
conditions. Thus, in the following system, nickel and cobalt
~as chlorides) gave 1 and 2 zones respectively, whereas the
mixture gave 3 zones corresponding to that of the individual metal
constituents. Further, the zones had 3 colors with sharply
distinguished pink and blue.
ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized)
11 21 ml. 1,2-propanediol cyclic 7.8-7.6 KV/1.25 ma
carbonate +9ml. methoxy 6 min. run
ethoxy ethanol +8 ml. r-Butyro-
lactone +3 drops Nitric acid
(1:30)
Another similar system resolves nickel and cobalt
mixtures into pink and blue colored zones. This system is parti-
cularly fast with certain nonpolar dyestuffs giving 5 cm/min
mobility rates at 7.5 KV levels. Operation at higher voltage
i level~ would increase further the mobility rates:
ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized)
12 21 ml. 1,2-propanediol cyclic 8.4-6.6 KV/1.25 ma
; carbonate +9 ml. methoxy
ethoxy ethanol +12 ml. bis
(2-methoxy ethyl) ether +3
drops nitric acid (1:30)
The rare earth groupings as well as hafnium and zir-
,
. .
: 19.
,; . .
106SZ74
conium repre~ent the most difficult elements for resolution.
Further, just a hafnium and zirconium form a particularly
close pair, within the rare earths 3 major paired groupings are
known. The following systems are useful for the transition
and heavy metal categories; including salts of the rare earths
- and zirconium - hafnium elements, such as those having an atomic
number of 21 and greater.
ELECTRICAL
CHARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized?
LO 13 15 ml. 1,2-propanediol cy~lic 3.6-7.2 XV/1.25 ma
carbonate +15 ml. methoxy3 min. run
ethoxy ethanol +13 ml. ethylene
carbonate +3 drops nitric acid ~
- (1: 30) ~ :
- Example 13 was successfully repeated with the medium
substantially the same except that in each run the ethylene
LS carbonate was replaced by one of the following: tetrahydrafur-
furyl alcohol, isophorone, "Cellosolve"*, ~yclohexanone, and 2-
ethylhexyl chloride.
In a system comprising propanediol cyclic carbonate,
nitric acid, methoxy methoxy ethanol and tetrahydrofurfuryl
alcohol in proportions similar to those above at 500V and 100~n,
the dye safra~ne ~ moved readily, and an orange contaminant
remained immoblle. This i9 an example of the separation of
components by reaching the threshold level for one compound in
a mixture.
Acidification with an inorganic acid is not essential
as the following example illustrates.
; ELECTRICAL
C}IARACTERISTIC
EXAMPLE SOLVENT FORMULAE (Stabilized)
14 12 ml. 1,2-propylene glycol14 XV/1.5 ma
+ 3 ml. dichloro acetic acid
~O +16 ml. ethoxy ethoxy ethanol
~ .
* Trademark
~-;
1()65~7~
Also, media containing bases such as triethanolamine
or ~-picoline in place of an acid, have the capability for the
separation of metals.
~; The application of this invention to organic compounds
is further illustrated by the following systems used for the
separation of sulfa drugs, sulfamerazine, sulfaguanidine and
sulfamethazine.
~ ELECTRICAL
Y CHARACTERISTIC
' : EXAMPLE SOLVENT FORMULAE(Stabilized)
20 ml. methoxy ethoxy ethanol 5.8-5.0 KV/1.25 ma
+ 12 ml. l-methyl 2-pyrrolidinone 4 min. run
+ 0.8 ml. dichloroacetic acid
The latter system, though found to be slow, was able to
yield differential zones with the dyestuff family of rhodamine
5 G, 6 G, and B, as well a~ a mixture.
The following media gave high resolution of the above
dyes in 20-25 seconds and mobility rates in excess of 12 cm/min.
ELECTRICAL
CHARACTERISTIC
~: EXAMPLE SOLVENT FORMULAE~Stabllized)
:
16 24 ml. 1,2-propanediol cyclic13.2 KV/0.8 ma
carbonate + 12 ml. ethylene
diacetate + 6 ml. salicylaldehyde
+ 3 drops nitric acid (1:30)
The following two very fast related formulae approach
, 20 cm/min mobility rates with excellent resolution:
~: ELECTRICAL
::~ CHARACTERISTIC
` EXAMPLE SOLVENT FORMULAE~Stabilized)
17 24 ml. 1,2-propanediol cyclic 14.2 KV/ma
carbonate + 12 ml. ethylene
- diacetate + 6 ml. salicylaldehyde
~; + .4 ml. ammonium bromide (saturated
in methoxy ethoxy ethanol~
,'
. ~ .
` ~ 21.
1~65274
18 24 ml. 1,2-propanediol cyclic car- 13-12.6 KV/ma
bonate + 12 ml. ethylene diacetate
+ 6 ml. salicylaldehyde + 2 ml.
ammonium bromide (saturated solution
methoxy ethoxy ethanol) + 2 ml. tri-
butyl phosphate + 4 drops tetramethyl
ammonium hydroxide (about 25~ in methyl
alcohol)
19 10 ml. tris-chloride ~0.14m) + 90 ml. 2 KV/ma
water Isucrose to 67%)
It is noted that urea or propylene glycol in such
systems, in concentrations to several molar, doesn't alter the
conductivity, although it may aid the mobility of protein
molecules. These substances act as a diluent or suppressant and
are useful in water solutions for biochemical separations of
substances such as proteins and enzymes. Albumin mobility in
such systems can exceed that of glycol soluble dyestuffs, as
shown below by the data for migration from the origin.
ELECTRICAL
; CHARACTERISTIC
EXAMPLE ~OLvENr FORMULAE (Stabilized)
16 ml. tris-chloride (.03M) 6 KV/2 ma
+ 40 ml. propylene glycol '~a~n"* #1
; + 50 ml. glycerin Albumin 1-1/4 -
1-1/2"
Soluble dye 3/4"
- 6 min. run
21 10 ml. tris-chloride buffer 7.2 KV/2 ma
(0.03M) Cellulose ace-
+40 ml. propylene glycol tate
+50 ml. methyi "Carbitol" Paper -
As discussed further below, the foregoing systems can
be improved in speed and degree of resolution using initiators,
suppres~ant~ and/or stabilizers.
Operation of this process was also carried out by
adding a sample to a bed of a gel made from agar, silica, and
gelatin. This procedure has been used to separate dyes, proteins
and other types of organic compounds. The media and electrical
. ~ademar3c
- ~ :
10`65Z74
characteristics were Rimilar to those described in the preceding
examples. Bulk separations have also been carried out in a
column with powdered minerals or cellulose supports.
A very useful system for non-polar substances, which
has resolved isomers of methyl naphthalene and provided good
resolution of Rhodamine B and 6G and food dyes is:
21 ml. propylene cyclic carbonate
9 ml. methoxy ethoxy ethanol
12 ml. tetrahydrofurfuryl alcohol
3 drops nitric acid (1:30)
10In the preceding formulae, use was made of various
- types of compounds to perform or provide different important
functions. For illustrative purposeC, a number of ~hese are
selected for arrangement into several categories according to
some of their common formulation functions. However, these
categories are not rigidly defined limitations for the use of
any compounds and some fall equally well across several category
boundaries. Thus, dimethyl phthalate is an example of a good
suppres~ant although it also functions as an inert base if used
as the base media. Further, it may act to insolubilize or
limit mobility or influence other factors, ther~by enhancing
resolution. Water is useful for a fairly active solvent with
moderate proton donor capabilitie3 and high dielectric constant.
This latter feature tends to maintain the chargeR once established.
However, water is generally less useful as a major constituent
at the higher voltage levels in non-externally cooled systems
due to its low boiling point.
TABLE I
Inert Media-base ~olvent, inert carrier,
Characteristic: solution limiter.
minimal conductivity p-cymene
23.
'
~106S~
;'
Inert Media-base, con't. formamide
mineral oil ammonium bromide
` n-decanol pyridazine iodide
l-octanethiol nitric acid
xylene mercaptoacetic acid
, Inhibitors (sup~ressant) Active Media Base
Characteristic: Characteristic: -
negative conductivity slight conductivity with
influqnce. tendency to enhance con-
> 10 tributyl phosphate ductivity of neutral
dimethyl phthalate media base.
triacetin potent solubilizer, solvent
s 2-ethyl hexyl chloride 2-chloroacetamide
Neutral media-base dimethyl formamide
Characteristic: N,N,-dimethylacetamide
,~ slight to poor conductivity l-methyl-2-pyrrolidone
:", .
with tendency for active dimethyl sulfoxide
change in conductivity with ethylene cyclic carbonate
dilution ~olvent, potent 2,5-hexanedione
solubilizer, coupling agent. Modifying agents
~-butyrolactone isophorone
1,2-propanediol cyclic carbonate nitrobenzene
propylene glycol salicylaldehyde
2-phenoxy ethanol 4-hydroxy~4-methyl-2-pentanone
2-ethyl, 1,3-hexanedlol ethylene diacetate
tetrahydrothiophene l,l-dioxide ~-picolLne
methoxy ethoxy ethanol o-dichlorobenzene
Conductivity Agents Very Active Media
Perchloric acid Characteristic:
dichloracetic acid strong conductivity
,
,"'
24.
SZ7~
Very Active Media, con't.
influence, proton donor
solvent action and acidity-alkalinity
diethyl ethyl phosphonate
- 5 N-cyclo-hexyl-2-pyrrolidone
bis (2-methoxy ethyl) ether
~exa methylene phosphoric triamide
amino ethyl piperaz~ne
imino bis propylamine
2,2'-imino diethanol
2-amino ethanol
triethylene tetramine
triethanolamine
mercaptopropionic acid
mercaptoacetic acid
A starting point for developing and choosing a solvent
media for particular chemical species is to determine those
. media which stabilize or are compatible with the species andwhich exert a good to excellent partition coefficient in a
standard chromatographic technique for the species on the sub-
strate to be used at various pH. The conductivity level is then
adjusted for use in this process by adding the solvent as a
major constituent to a compatible media base system which has
: a properly adjusted conductivity or, the conductivity of the
solvent can be tailored to form a media base system by the use
of the types of agents described in Table I. Mobility is
normally achieved at about 1.25 ma, which generally exceeds most
threshold current levels. Further adjustment may be necessary
to initiate or refine the mobility of the species by the adjust-
ment of the composition of the system as indicated above.
~ 1065Z74
For example, adjustment may be made by the use of complexing
agents, modifying agents, similar solvents as determined by
chromatographic screening, by pH adjustment and less active
substrates (such as "Teflon"*).
The compo~nds listed herein are representative of a
s : . .:
much vaster possible grouping of like or related materials
useful as solvents, cosolvents, coupling agents with moderate,
~;~ strong or nil effects on conductivity; many form complexes and
, . . .
; metal adducts substantially modifying the effective properties
. 10 of the compounds or materials involved.
These materials are often used in comixtures to achie~e
their desired combined properties. Such formulations, aside from
their electrical properties, achieve a very broad scope of
applicability for diferent classes of molecular species.
The following list of substances may be considered
Ln three main categories, given below. Other factors to be
considered are a larger liquidity range, and dielectric constant,
low viscosity, water compatibility and miscibility and strong
donor/acceptor influence or neutrality:
1. The major grouping has boiling points at or above -
160~C which are liquid at or near room temperature. Generally
they have good solvent action.
.. . .
; 2. A number of the compounds listed having boiling
~ . .
` points in the 130-160C range, or melting slightly above room
temperature. These are often used in lesser percentages to
modify systems. Also, they often can be liquified with a minor
amount of cosolvent.
3. The remainder are modifying agents, ~hose melting
!~ ~ points may be substantially higher and which are used in solution
with other media.
26.
* Trademark of the DuPont Company for poly(tetrafluoroet:hylene)
resin (PTFE). Its properties and characteristics are as
described in m e Merck Index, 8th Ed. (1968) p. 849.
. .
. - .
.,; , . . .
` ` ` ~065274
. . Based upon physical characteristics, chro~atographic
: screening tests, and the media.adjustment techniques described
herein, the following compounds are representative of the type
; i~ of media component useful in this process:
TABLE II
Alcohols 2-(hydroxymethyl)-2-nitro-1,
- 3-propanediol
2-aminoethanol
. 2-ethylaminoethanol phenol
2,3-epoxy-1-propanol aziridine ethanol
ethylene dinitrile tetraethanol hydroxy ethyl piperazine
2,2-iminodiethanol piperazine ethanol
dl-menthol 5-hydroxy-2-(hydroxymethyl)-
: - 4H-pyran-40ne
2 mercaptoethanol
furfuryl alcohol 2-(2-ethoxy ethoxy) ethanol
tetrahydro furfuryl alcohol 2-[2-(ethoxy ethoxy) ethoxy]
.: ethanol
:. 2,2'-oxydiethanol
2,2'2"-nitrilotriethanol 2-(2-butoxy ethoxy)ethanol
1,1'1"-nitrilotri-2-propanol 1-[[ [2-(2-methoxy-1-methyl-
ethoxy)]-l-methyl ethoxy]]-
.. l-phenylethanethiol 2-propanol
2,2'-(phenylimino)diethanol n-butanol
1,3-propane dithiol 1,3 butanediol
: thiodiethanol 1,4-butanediol
4-pyridine propanol 2-~2-butoxy ethoxy) ethanol
2-nitro l-propanol 2-butoxyethanol
. .
2-nitro-1-butanol 2-(2-methoxy ethoxy) ethanol
2-amino-2-~hydroxymethyl)-1, 2-methoxy ethanol
3-propanediol
3-methoxy-1-butanol
~ geraniol 2-butoxy-ethanol
: . 2-methylamino ethanol 2-ethyl hexane-1,3-diol
2-methyl-2-nitro-1, . t-butanol
3-propane diol
.
27.
.. . ~ . . . . .
.. : . . .. :
1(~65Z74
Alcohols (cont'd)
iso-amylalcohol dimethyl phthalate
caprylic alcohol diethyl phthalate
decanol ethyl lactate
dehydroisophytol ethyl malonate
~- glycerin di iso octylazelate
; dehydrolinalool di-2-ethyl hexylazelate
thioglycerol methyloleate
3-chloro-1, 2-propanediol tri (n-octyl) mellitate
2-amino-1-butanol tri (n-decyl) mellitate
2-amino-2-ethyl-1,3, propanediol acetyl tributyl citrate
2-amino-2-methyl-1-propanol tributyl citrate
2-Dimethyl amino-2-methyl-1- ethylene diacetate :.
: propanol
tributyl phosphate :
sorbitol triethyl phosphate
glucose tricresyl phosph~te
sucrose triphenyl phosphate. .
. ethylene glycol tri(2-ethyl hexyl) phosphate
. propylene glycol tributoxy ethyl phosphate
20 dipropylene glycol o,o,o-triethyl phosphorothioate
~ polyethylene glycol diethyl ethylphosphonate
thiodiethylene glycol dibutoxy ethyl sebacate
l-octanethiol 2-ethyl hexylchloride
4-hydroxy-4-methyl-2-pentanone bis [2-(2-methoxy ethoxy)
ethoxy] ether
linalool
linalool oxide bis (2-methoxy ethyl) ether
Ethers, esters 2~methoxy ethyl acetate
dibutyl phthalate ethoxy ethyl acetate :
phenyl acetate 2-(2-butoxy ethoxy) ethylacetate
dibutyl fumarate diethylene glycol monomethylether
' - ' ~
.
- ,.
. ~ 28.
~- ~06S27~
.,
~ Ethers, esters (cont'd) di propylene glycol dibenzoate
".
diethylene glycol monoethyl polyethylene glycol (200)
ether dibenzoate
'
ethylene glycol monoethyl tri ethylene glycol diacetate-
ether acetate
~:: bis (diethylene glycol mono
.. ~ ethyl ether) phthalate-
n~ ethylene glycol mono ethyl
. ether acetate
~, bis (2-ethyl hexyl) adipate
ethylene glycol monohexyl ether 1,2-bis (2-chloroethoxy) ethane
.: diethylene glycol monoethyl bis (2-chloroethyl) carbona~e
: 10 ether acetate
bis (2-methoxy ethyl) phthalate
s diethylene glycol monomethyl di mercaptodiethyl ether
ether
. - glycol di mercaptoacetate
. ethyl cyanoacetate di methyl thiodipropionate
`. 3-acetyl-3-chloropropyl acetate tri methylol ethane tri (3-
~,: mercaptopropionate)
`, butyl chloroacetate
,,
~ butyl lactate pentaerythritol tetra (3-
,~. mercaptopropionate)
. . butyl stearate
dl tetra hydro furfuryl adlpate bis (2-chloro-isopropyl) ether
,. . .
tetra hydro furfuryl oleate glycerol triacetate
~.
'. 20 tris (chloro ethyl) phosphate glycerol tripropionate
,,
2,2,4-trimethyl-1,3-pentanediol 1,2/1,3-glycerol diacetate
. diisobutyrate
hexyl acetate
~,
. di ethoxy ethyl phthalate ethylmethyl carbamate
,, . methoxy ethyl ricinoleate hydroxy ethyl acetate
,;
,` glycerol monoacetate phenyltrimethoxy silane ~:
~j , .
di n-hexyl adipaté trimethoxy trimethyl mercapto
~, silane
; glycerol tributyrate :~
butane diol dicaprylate dimethyl polysiloxanes
, ethylene glycol dibenzoate 1,2-bis (2-methoxy ethoxy)ethane
' 30 di ethylene glycol dibenzoate 2-(ethoxy ethoxy) ethylacetate
, - 29 -
.
6S~74
~ . .
Ethers, esters (cont'd) 2,5-hexanedione ~ -
` di~enzyl ether 6-hexanolactone
: Amides l,2-propanediol cyclic carbonate
formamide oxohexamethylenimine
S N,N-dimethyl acetamide 2,3-butanedione
2-chloroacetamide . ethylene trithiocarbonate
urea propiolactone :~.
l,1,3,3,-tetra methyl urea 2-piperidone
acrylamide ~ n-butyl carbonate
lO cyanamide 4,4,4,-trifluoro-1,2
~ thienyl-1,3-butanedione
.. . N,N-bis (2-cyanoethyl) formamide :~ -
. 2-cyanoacetamide 2,4-pentanedione
2-furamLde dipropyl carbonate
N-2 hydroxy ethylformamide 2,4-pentanedione
. 15 N-ethyl p-toluene sulfonamide Nitriles_
N-ethyl-o-toluene sulfonamide ethylene dinitrile tetrace-
.-: tonitrile
N-2-hydroxy ethylacetamide
methane sulfonamide pimelonitrile
N-(2-methoxy ethyl) acetamide 3,3-thiodipropionitrile
N,N'-methylene ~is acrylamide 3,3-oxydipropionitrile
- N-ethyl formamide phenylacetonitrile
. N-methyl formamide hydracrylonitrile
: thioacetamide imino diacetonitrile
picramide p-methoxyphenyl acetonitrile
hexamethyl phosphoric triamide glutaronitrile
formamidine acetate succinonitrile
. ~, . . Lactones, lactams, dioneQ, picolino nitrile
: and carbonates
' nicotinonitrile
~ ethylene cyclic carbonate benzonitrile
:- 30 -butyrolactone ethylcyanoacetate
. . . , ' ':
,'~. ~ .
. ' .
~ ~ 30.
,.. :,....
- ,
1065Z74
- Nitriles (cont'd) mineral oil
4-chloro 2-hydroxybutyronitrile dichlorophenyl trichlorosilane
3,3'-12,2-Bis(2-cyano ethoxy octadecyltrichlorosilane
methyl)- trime~lene
dioxyl dipro2yl~nitrile diphenyl dichloro silane
S Aldehydes, ketones, thiones, epibromohydrin
miscellaneous compounds
1,1,2,2-tetrabromoethane
r 2'-hydroxyacetophenone 1,2,3,4- tetrahy~naphthalene
f~alicylaldehyde tetrachloroethane
fenchone 1,2,4,-trichloro~enzene
4-anif~aldehyde indene
o-chlorobenzaldehyde pyrrolidinone
if~ophorone l-butyl-2-pyrrolidinone
. cyclohexanone l-cyclohexyl-2-pyrrolidinone
2-piperidone Bafsic Compounds - and amines,
hydroxides, oxides, sulfides,
. lS 2-furaldehyde hydrates, alcoholates, hetero-
l-methyl-2-pyrrolidinone cYclics
2,6-dimethyl-4-heptanone iodine chloride-iodine systems
p-cymene sulfur chloride-iodine systems
o-dichlorobenzene benzyltrimethylammonium hydroxide
o-nitrotoluene betalne hydrate
;- nitrobenzene chollne
i~osafrole n-ethyl morpholine
o-methoxy benzaldehyde 2,6-dimethyl morpholine
tetrahydroionone hexamethylene tetra-amine
pyridazine lodide 2-picoline-1-oxide
decahydronapthalene tetramethylammonium hydroxide
diphenyl methane tetrabutylammonlum hydroxide-
durene tetramothyl guanidine
d-limonene 3-ethyl-4-methylpyridine
. 30 turpentine 5-ethyl-2-methylpyridine
: .
~ 31.
f '
.:
.
- . '
- ~065;~7~
hexamethylene imine 3,5 lutidine
tetrahydrothiophene l,l-dioxide Acidic Media
dimethyl sulfoxide methane sulfonic acid
imino-bis-propylamine dichloroacetic acid
triethylene tetramine mercaptoacetic acid
butyraldoxime 3-mercaptopropionic acid
2-amino-4-methyl thiazole propionic anhydride
n-propyl sulfoxide lactic acid
n-butyl sulfoxide 2-chloropropionic acid
. .
alpha picoline propionic acid
: beta picoline sulfoacetic acid
quinoline trichloroacetic acid
1,2-diazine (ethylene dinitrilo) tétra-
acetic acid
aminoethyl piperazine
2-methyl-5-ethyl pyridine trimethylacetic acid
N-hydroxy ethyl piperidine picric acid
3-ethyl-4-methyl pyridine camphoric acid
4-ethyl pyridine hexanoic acid
,,~ 2,4 lutidine picramic acid
2,6-dimethyl pyridine-N-oxide cyanuric acid
Lewis bases picrolinic acid
: 3-methyl piperazine Lewis acids
4-methyl piperidine p-toluenesulfonic acid
4-methyl thiazole trifluoroacetic acid
2-methyl thiazole amino imino methane sulfonic
acid
2-methyl tetrahydro furan
tetrahydrothiazole amino ethane thio sulfuric
acid
1,4 oxathiane
r' 1,2,3-azimidobenzene 2-amino ethyl hydrogen sulfate
2-amino-1,3-bis (2-ethyl hexyl)- perchloric acid
5-methyl hydropyrimidine
sulfamic acid
- 32 -
1065274
. Acidic Media (con't) ammonium bromide
: phosphoric acid lithium bromide
sulfuric acid lithium iodide
nitric acid morpholine oleate
Salts lithium nitrate
: betaine hydrochloride lithium hydroxide
choline chloride cesium acetate
. hydroxylammonium acetate cesium chloride
- hexadecyltrimethyl ammonium cesium carbonate
: bromide
cesium salicylate
i guanidine nitrate potassium iodide
tetrabutyl ammonium iodide poly vinyl benzyl trimethyl
ammonium chloride
tetra ethylammonium bromide
tetra methyl ammonium bromide hydroxylammonium acid sulfate
. 15 1,1,1, trimethyl hydrazonium Lewis salts
iodide
acetylcholine bromide
: acetylcholine iodide
aminoguanidine nitrate
~: 20 6-amino-3-indazolinone
dihydrochloride
cyanuric chlorlde
guanidine acetate
.' guanidine hydrochloride
amino guanidine bicarbonate
2,2'2" nitrilo triethanol hydrochloride
semicarbazide hydrochloride
ammonium formate
ammonium thiocyanate
ammonium nitrate
~ 33.
,, .
1065Z74
.
F~rmulation of the EM2 media is fundamental. It has
been found that compounds or mixtures with a large liquidity
range are particularly suited for use in EMP, especially those
liquids with a glassy or vitreous structure. These compounds
- 5 or mixtures apparently have an inherent structure which facili-
tates regulation of proton donor/acceptor properties and
electron charge transfer, as well as providing the advantage of
low evaporation. It is sometimes practical to use high boiling
point li~uids because the practice of EMæ at or above higher
bhre~hald currents does generate some heat. Media with higher
or lower melting and boiling components may be used for special
applications.
Components used in EMP media formulation should have
, a number of characteristics if they are to be maximally useful.
Water and solvent miscibility are often desired, as is general
solvent action, availability, and thermal, shelf, chemical and
electrical stability. Superior solvent activity is not always
desired. It is feasible to limit or cause differential movement
when two or more transportable chemical species are present in
the media by using media components which are poor solvents for
one or more species. Below is a list of additional compounds
useful for their solvent action or their ability to mediate
such properties in other materials. Also included are tracer
agents which will be discussed more fully hereinafter.
34.
. ~ ~
106S274
:~ ,
- T~E ~
HYDROXY, ETHER COMPOUNDS
1,2,4-Butanetriol Dodecyl alcohol poly-
,,!` ~ o-Tert-butyl phenol oxyethylene ether
2,2-Bis (hydroxy methyl) 2-(Ethyl thio) ethanol
propionic acid Ethynyl cyclohexanol
2,3-Butanediol Ethynyl cycloheptanol -- -
1,4-Butanediol diglycidyl Ethynyl cyclooctanol -~
ether Glycidol
2-Butene-1,4-diol Guaiacol
., .
2-(n-Butylamino)-ethanol 1,2,6-Hexanetriol
. Butylhydroxytoluene Hydroxy acetone
. 2-Butyne-1,4-diol 3-Hydroxy camphor
Cetyl Alcohol 2-Hydroxy cyclodecanone
. Chloral 2-Hydroxy ethyl ether
Cyanoethyl sucrose 2-Hydroxy ethyl hydrazine
. ~ Dichlorotriethylene glycol N-Hydroxy ethyl morpholine
,. ~ Hydroxy acetone 2-(Hydroxy methyl)-2-ethyl-l,
i; 2,2-Diethyl-1,3-propanediol 3-propanediol
2,5-Dihydroxy methyl pyrrole l-(Hydroxy methyl)-5,
: 1,3-Dimercapto-2-propanol 5-dimethyl hydantoin
2,3-Dimercapto-l-propanol 2-Hydroxy ethyl methacrylate
Dimethoxy tetra ethylene l-(~-Hydroxy ethyl)2-methyl-
glycol 2-imidazoline
2,3-Dimethyl-2, 3- 4-Hydroxy-3-methyl-2-butanone
: butanediol 2-Hydroxy-3-methyl cyclopenten-
, Dimethylol propionic l-one hydrate
acid 3-Hydroxy-2-methyl-4-pyrone
: 2,2'-Dithiodiethanol 5-Hydroxy oxindole
o-Ethyl phenol 3-Hydroxy piperidone
- 35 -
, .
.
-- ~065;;~74 ~
.: . .
HYDROXY, ETHER COMPOUNDS (cont'd)
2-Hydroxy pyridine 1,3-Dichloro-2-propanol
5-Hydroxy-4-octanone 2,3-Dichloro-l-propanol
Iodopropylidene glycerol 2,4-Dichloro phenol
N-Methylol-2-pyrrolidone 1,3-Dichloro-2-methyl-2-
Anilino ethanol propanol
Amyl ether Diethanol sulfide -
Benzene thiol ~ ~C~-Dimethyl phenethyl alco-
Benzyl alcohol hol
~: 10 Benzyl butyl ether 2,4-Dimethyl phenol
n-Benzyl ethyl ether 2,6-Dimethyl phenol
2-Benzyl oxythanol 4,6-Dinitro-o-cresol
:,
4-Bromodiphenyl ether 2,4-Dinitro phenol
n-Butyl phenyl ether 2,6-Dinitro thymol
: n-Butyl diethanolamine 2,3-p-Dioxanediol
l-Chloroethyl "Cellosolve"* Diphenyl ether
l-Chloro-3-pentanol 2,6-Di-tert-butyl-p-cresol
4-Chloro cyclohexanol 2,6-Di-tert-butyl phenol
6-Chlorol-l-hexanol 2,4-Di-tert-pentyl phenol
o,m,p-Cresols 6,6-Dimethyl bicyclo 3,1,1
o,m,p-Chlorophenols hept-2-ene-2-ethanol
6-Chloro thymol Dodecyl alcohol
2-Cyano ethanol p-Dodecyl phenol
Cinnamyl alcohol l-Dodecane thiol
. Cedrol 1,2-Ethane dithiol
Cyclohexanol Ethane thiol
1,4-Cyclohexan di- l-Ethoxy naphthalene
methanol o-Ethoxy phenol
Decanediol Glycerol di methyl ether
2,3-Dibromo-l-propanol 3-Hydroxy propionitrile
*Trademark for the (l-chloroethyl) ether of ethylene glycol.
- 36 -
'. ~ : ' ':
~ 106SZ74
. ~ .
HYDROXY, ETHER COMPOUNDS (cont'd)
~; 3-Hydroxy propylene oxide Poly ethoxy ethylated (1-20)
1,6-Hexanediol oleyl alcohols
Hexyl "Cellosolve" Polyethoxylated lanolin (5+) ~ .
, D-Methoxy phenol alcohols
~.,:,;
Dl-ct-Methyl benzyl alcohol Polyethoxylated (75) lanolin
5-Methyl-2-isopropyl phenol Polyethoxylated (9) acetyl
....
:~ 2-Methyl-1,2,3-propanetriol lanolin alcohol
~, . 2-Imidazoline-l-ethanol p-Butoxy phenol
~ 10 5-Indanol Polyglycols
:~- 2-(Iso propyl thio) ethanol Polymethyl alkyl siloxanes
, : Lanolin alcohols, acetylated Pyrrole-2-ethanol
: 5-Methyl-1,3-dioxane-5- Pyrrole-2-methanol !
methanol Stearyl alcohol
::x :: 2-Nitro-2-ethyl-1, 2,5-Tetra hydrofurandimethanol
3-propanediol 1,2,3,4-Tetra hydro-2-naphthol
2-Nitro-2-methyl-1-propanol Tetra hydro pyran-2-methanol
o-Nitro anisole Tetra hydro-2)2)5-trimethyl-5-
.' o-Nitro phenol cinyl furfuryl alcohol
: 20 2-Methyl-l-phenol-3-butyne-1, Tetrahydropyran-2-methanol
.~ 2-diol 2,2,4,4-Tetramethyl-1,3-
m-Nitrobenzyl alcohol cyclobutanediol
,~ 2-Nitroethanol Tetra ethylene glycol
1,5-Pentanediol 2-Thenyl alcohol
Pentaerythritol Thiobenzyl alcohol
. p-Pentoxyphenol 2,2'-Thiodiethane thiol
.~ Phenethyl alcohol 2,2-Thiodiethane thiol
Sec. Phenethyl alcohol Triethylene glycol dimethyl
l-Phenyl-1,2-ethanediol ether
-- 1,1,1-Trichloro-2-propanol
h
~ 37 -
:
, ' .
.
~ 1065274
- HYDROXY, ETHER COMPOUNDS (cont'd)
l,l,l-Trichloro-2-methyl-2- Crown ethers
propanol (& hydrate) Trimethylol amino ethane
l,l,l-Trimethylol ethane l-(2-Hydroxyethyl) piperazine
Trimethylolpropane p-Hexyl phenol
Tris (hydroxy methyl) nitromethane p-Hexyl oxyphenol
Toluene-3,4-dithiol o-Phenyl phenol
Aldol 2,4,5-Tr.ichlorophenol -
l-Amino-2-propanol 2,4,6-Trichlorophenol
3-Amino-2-propanol 2,2,2-Trichloro-l-ethoxy
3-Amino-2-butanol ethanol
2-amino thiophenol 2-Vinyl oxyethyl ether
2-Methyl-2,4-pentanediol 2,4,6-Trinitroresorcinol
2-Methyl cyclohexanol o,p-Toluenethiol
3-Methyl cyclohexanol 3-Cyclohexene-l-methanol
4-Methyl cyclohexanol 3-Cyclohexene-l-dimethanol
2-Methyl-l-phenyl propanol-l 3-Nitro-2-butanol ~ -
2-Methyl-l-phenyl propanol-2 2-Nitroethanol
p-(Methyl thio) phenol 2-Nitro-l-propanol
~: 20 2-Nitro diphenyl ether AMIDES, IMIDES
l-Octanol 4-Acetami.no-2,2,6,6-tetra
1,2,3-Propanetriol methyl piperidino-l-oxyl
l-Phenyl-2-propanol 2-Acetamido-3-butanone
3-Phenyl-l-propanol 4-Acetamido butyric acid
2,2,4,4-Tetra methyl-l, 4-Acetamidothiophenol
3-cyclobutanediol 2-Acetamido thiazole
p-(1,1,3,3)-Tetra methyl 2-Acetoacetamido-4-methyl
butyl phenol thiazole
Thiophenol Adipamide
m-Thiocresol N-Allyl methacrylamide
- 38 -
'
1065~274
MIDES, IMIDES (cont'd)
6-Amino nicotinamide N-Ethyl acetamide
Anthranilamide Ethyl acetamido acetate
Azodiacarbonamide N-Ethyl acrylamide
N-Bromoacetamide N-Ethyl maleamic acid
2-sromo-2-ethyl Iso valeramide 3-Ethyl-3-Methyl gIutaramide
N,n-Butyl acry1amide N-Ethyl methacrylamide
N-Butyramide N-Ethyl nicotinamide
Iso-butyramide N-Ethyl propionamide
Chloral formamide Ethyl oxamate
Cinnamamide Fluoroacetamide
Diacetamide Fumaramide
N,N'-Diallyl tartardiamide l-Glutamide
,.. .
N,N-Dibutyl formamide Glutaramide
2,2-Dichloroacetamide Heptamide
N,N'-Dicyclohexyl carbo N,N-Hexamethylene formamide
diimide Hexa methyl phosphorous triamide
Diethyl formamido malonate 2,2,2-Trichloroacetamide
N,N-Diethyl Iso nico- N-Hydroxy acet~mide
tinamide 2-Hydroxy ethoxy acetamide
N,N-Diethyl nicotinamide N-(2-Hydroxy ethyl?-phthalimide
N,N-Diethyl nipecotamide N-(Hydroxy methyl)-nicotinamide
N,N-Diethyl-l-piperazine N-Hydroxy succinimide
carboxamide 5-Hydroxy valeramide
N,N-Dimethyl acetoacetamide Iodo acetamide
N,N-Dimethyl nicotinamide Iso-nicotinamide
3,3-Dimethyl glutaramide Iso-nipecotamide
2,4-Dihydroxybenz~mide N-Iso propyl acrylamide
2,3-Epoxy-2-ethyl N-Iso propyl salicylamide
hexanamide N-Lauryl methacrylamide
N,N'-Dimethyl oxamide 3,5-Dinitrobenzamide
."
" ` ' .
~ 39.
... .
65Z74
AMIDES, IMIDES (cont'd)
Maleamic acld N,N,N',N'-Tetra ethyl
Maleimide phthalamide
Maleondiamide N,N,N',N'-Tetra ethyl
N-Methyl acetamide fumaximide
N-Methyl acrylamide N,N,N',N'-Tetra methyl
N-Methyl maleimide carbamide
2-Methyl malonamide Thiobenzamide ~ :
~, . .
N-Methyl nicotinamide Thionicotinamide -
N-Methyl propionamide o,p-Toluamide
N-Methyl 2,2,2-Trifluoroacetamide 2,2,2-Trifluoroacetamide
Methyl-2,2,2-Trichloroacetamide Trimethylacetamide
P-Nitrobenzamide Valeramide :-
Oxamic acid . l-Naphthaleneacetamide
Oxamide 4-Acetamido-2,2,6,6-tetra
: ~-Phenyl butyramide methyl piperidine
Phenyl formamide N-Butylacetamide
N-Phenyl succinim{de tert-Butyl carbazate
Phthalamide Diacetone acrylamide
20 N-Polyoxy ethylene fatty N,N-Diallyl formamide
acid amides Dibutyl cyanamide
Propionamide N,N'Dibutylpropionamide
. Pyrazinamide N,N-Diethyl acetamide
Stearamide Diethyl acetamido malonate
Succinimide N,N-Diethyl butyramide
Succinic diamide N,N-Diethyl formamide
Sulfabenzamide N,N-Diethyl ~ropionamide
Sulfacetamide N,N-Diethylm-toluamide
Sulfamide . N,N-Dimethyl dodecanamide
N-Sulfanyl stearamide N,N-Dimethyl propionamide
.
'
,.,
,
:: ' , ' ' , , ' - -. .
- , .~ .
1065Z74
AMIDES, IMIDES (cont'd)
N,N,-Dimethyl thioacetamide Phenyl carbonimide
N,N-Dimethyl thioformamide Acetamidine acetate
:~ N,N-Dimethyl valeramide p-Acetamido benzaldehyde
3,5-Dinltro-o-toluamide p-Acetamido benzoic acid
N,N-Diphenyl acetamide N-[2-(Acetamido)-imino]
N,N-Dipropyl acetamide diacetic acid
~ .
N,N-Dipropyl decanamide ESTERS, CARBONA~ES
N,N-Dipropyl propionamide Allylidene Diacetate
N-Ethyl maleimide Bi~ (2-Ethyl hexyl)sebacate
Ethyl methyl carbamate Bis (2-Ethoxy ethyl) sebacate
Hexanamlde Bis ~2-Ethyl hexyl) phthalate
Hexaethyl phospho~ triamide n-Butyl oleate
2-Hydroxyethyl carbamate Butyl nitrite
N-2-~Hydroxy ethyl) 2-Chloro ethyl trichloroacetate
auccinimide 2-Chloroethyl chloroacetate
2-Furamlae 6,9-Diamino-2-othoxy
Lactamide acridine lactate
N-Methyl benzamide Di isopropyl adipate
N-Methyl diacetamide Dlmethyl methyl phosphonate
N-Methyl-N-l-naphthyl 2-Di isopropyl aminoethyl-p-
; acetamide amino benzoate
N-Methyl-2-phenyl acetamlde Di iso-butyl carbonate
N,N,N',N'-Tetra methyl Dibutyl sulfite
glyclnamide Dlbutyl ~+) - tartrate
N,2,2-Trimethyl propionamide Dimethyl maleate
2,2,5,5-Tetra methyl-3- Dimethyl malonate
pyrrolin-l-glyoxy-3- D~ethyl oxalate
- car~oxamide Dlbutyl oxalate
30 l-Naphthaleneacetamide Dlethyl adipate
; 41.
.
- . . .
` `` 106S274
. ESTERS, CARBONATES (cont'd)
.
Dipropyl adipate Methyl abietate
Dibutyl adipate . Methyl acetoacetate
Diethyl sebacate Methyl benzoate
Di iso-butyl adipate Methyl trichloroacetate
Di-n-butyl.sebacate n-Octyl nitrate
Dimethyl phosphite Phenyl carbonate
Ethyl trichlorcacetate Polyoxy ethylene stearate
Ethylene (mono) thio carbonate Isopropyl salicylate
: 10 Ethyl-2-pyridine carboxylate . n-Propyl nitrate ;:
: Ethyl anthranilate Phenyl acetate
Ethyl acetoacetate Propyl benzoate .
Ethyl benzoate . Tetra hydrofurfuryl nicotinate
2-Ethyl hexyl acetate Tetrahydro furfuryl acetate
Ethyl dichloroacetate Tetra nitro methane
Glucose-1-phosphate 2,2,2-Trichloro ethyl carbamate
Glycol diformate Trilauryl phosphite
IRO butyl carbonate Trilauryl trithiophosphite
Iso-pentyl nitrite Trimethyl-3,3',3"-
Iso-propyl salicylate nitrilotripropionate . -
. . Methyl cyanoacetate Trimethyl phosphate
Methyl cinnamate Triethyl orthopropionate
Methyl decanoate . Triethyl orthopropionate
: Methyl myristate Triethyl phosphite
. 25 Methyl octanoate Tri Isopropyl phosphite
Methyl palmitate Tri butyl borate
Methyl salicylate Tri (2-Tolyl) phosphite
Methyl stearate Tetra hydrofurfuryl propionate
Monostearin --
Monolein --
:- :
': ~ 42.
.
. . - :, ,. ,: : :
- ' ~ ,,: .. ' . ,: ~ : :
- . .
-
" ~065Z'74
i .
KETONES, ALDEHYDES
2-Acetyl cyclohexanone N-Morpholino carboxaldehyde
- Acetaldehyde Nicotinaldehyde
Anisole 5-Nitro salicylaldehyde
Butyraldehyde Nitroso salicylaldehyde
: Butyrophenone 2-Octanone
p-Chlorophenetole l-Phenyl-2-propanone
Cinnamaldehyde Phenetole
1,2-Cyclohexanedione Picolinoaldehyde
1,2-Cyclodecanedione l-Piperazine carboxaldehyde
3-Cyclohexene-l-carboxaldehyde 1,4-Piperazine
1,3-Dichloro-2-propanone dicarboxaldehyde
Decanone N-Piperidino carboxaldehyde
2,5-Dimethyl cyclohexanone Piperonal
- 3,5-Dimethyl-5-ethyl-2,4-dione Propiophenone
N-Formyl hexamethyleneimine 2-Pyridone
Hexachloroacetone 4-Pyridone
2,4-Imidazolidine dione Pyridine-2-carbaldehyde
2-Imidazolidone Pyridine-3-carbaldehyde
: 20 Indole-3-cyclohexanone Pyrrole-2-carbaldehyde
L-Menthone Thiophene-2-carbaldehyde
4-Methoxyacetophenone Tribromoacetaldehyde
Methyl benzophenone Veratraldehyde
o-Methyl anisole o,p-Vanillin
4-Methyl acetophenone o-Phthaldialdehyde
c~-Methyl cinnamaldehyde 1 Phenyl-3-pyrazolisinone
2-Methyl piperazine-N, 2-Heptanone
~: N'-dicarboxyaldehyde Pentaerythritol diformal
N-Methyl pyrrole Methyl-2-thienyl ketone
carboxaldehyde Cyclododecanone
Azacyclotridecanone
- 43 -
- 1065Z74
HETEROCYCLICS, ACIDS, AMINES
( & SALTS), MISOELLANEOUS SUBSTANCES
N-Acetyl morpholine Butyl disulfide
2-Acetyl pyrrole Tert-butyl disulfide
s 2-Acetyl thiophene 9-Chloroacridine
Acridan 4-Chloromethyl-l-aeridine
Acridine 2-Chloropyridine
4-Chloropyridine
Acrldine orange ~ Cyclopentamethylene
0 Acridine yellow tetrazole
Acriflavine 3,6-Diamino acridine
Allyl thiourea 1,8-Diamino-p-menmane
l-Allyl pyrrole 1,2-Diazole
2-Allyl pyrrole Dihydroacridine
.. .5 Amino acid~ 1,2-Dihydro-3,6-
9-Amlno acridlne pyridazinedione
3-Amlno acridlne 2,3-dihydrofuran
~ o-Aminophthalhydrazide 3,4-Dihydro-1(2H)-
- ~enzothiazole naphthalenone
~0 N,N'3is ~3-amino propyl)- Dimethyl acid pyrosphosphate
. .
piperazine 2,5-Dihydroth~io~hene 1, 1-
~ Bi~ (2-Ethyl hoxyl) dioxide
orthophosphoric acid 2,3-Dihydro-4-pyxan
2,2-Bis ~-thyl sulfonyl 2,4-Dlmethyl-3-ethyl pyrrole
!5 butane 2,3-Dimethyl-4-ethyl pyrrole
. 1,8 Bi~ ~dimethylamlno)- 2,5-Dimethyl pyrrole
naphthalene 3,4-Dlmethyl-5-sulfanilamido
3utyl ~ulfone iso oxazole, salt~
; ~is ~2-ethyl hoxyl) D1 ~henyl ~ulflde
- 30 hydrogen phosphate Di i~opropanolamino
.;
.
: 44.
. .
.
.
.. ..
~ - ` 106S~74
HETEROCYCLI CS, ACI DS, AMINES ( & SALTS )
MISOELLANEOUS SU~STANCES (cont'd)
Dichloro propionic acid 2-Nitrofuran, 3-Nitrofuran
N-Nitroso diethylamine l-Nitrosopiperidine
l-Nitrosopiperidine Oxypolygelatin
Dibutyl butylphosphonate Pantoic acid- ~ }actone
o~-Glucose-l-phosphoric acid 1,5-Pentamethylene-tetrazole
Gluconic acid o-Phenetidine
. Guar Gum Phenyl hydrazine
0~ Indole Phenyl mercuric borate
. Imidazole p-Phenetidine
Iminodiacetic acid 4-~-3-Phenyl propyl)-
Hexamethylene imine pyridine
3,5-Lutidine-N-oxide Phenyl phosphonous
.5 2-Lactoyl oxypropanoic acid dichloridate
Lithium acetate Phenyl phosphoro dichloridate
.
, Lithium perchlorate Phenyl phosphone thioic
.- l-Methyl imidazole dichloride
2-(Methyl thio) benzothiazole
0 2-Methyl glutaronitrile
Methyl isobutyl ketoxime
- Methyl phenyl sulfide Phenyl phosphoric dichloride
. , l-Methyl-l-phenyl hydrazine Piperine ::
3-Methyl sulfolane Pyridine-l-oxide
, '5 N-Methyl pyrrole Pyridazine
'. Nepatolactone Pyrimidine
!......... Nitrocyclohexane Pyrrole
o-Nitrophenol Quinoxaline : :
i 2-Nitropyrrole Safrole
0 o-Nitroanisole Stearic acid
.,
~ ' :
:
4 5
.. . . . ... ..
~065274
HETEROCYCLICS, ACIDS, AMINES ( & SALTS)
MISCELLANEOUS SUBSTANCES (cont'd) -
Trimethyl sulfoxonium iodide Caprylic acid
1,2,3-Trimethyl benzene l-Chloro octane
1,2-Epoxycyclododecane Chloropicrin
N-(3-Amino propyl)-2- Caproic acid
pyrrolidinone o-Chloroaniline
N-(3-Amino propyl)-morpholine Cumene
Acetonaphthane 2,4-Dichloropyrimidine
4-(2-Amino ethyl) morpholine 3,~6-Dichloropyridazine
N-(3-Amino propyl)-morpholine 3,7-Dichloroquinoline
n-Butylaniline 2,5-Dihydro-2,5-dimethoxy
: Butyl sulfide furan
Benzylamine N,N-Dimethyl cyclohexylamine
Benzedrine 1,4-Dimethyl piperazine
2-Benzyl pyridine 1,4-Dinitroso piperazine
l-Bromonaphthalene 2,3-Dichlorodioxane
Butyl benzene 1,5-Dichloropentane
l-Bromo-2-iodobenzene Dibenzylamine
1-Bromo-3-iodobenzene N,N-Dibutyl aniline
Butyl nitrite Dipentylamine
Cyclododecane 1,3-Dioxepane
1,5,9-Cyclododecatriene 1,3-Dioxolane
Cyclododecene 2-(1,3-Dioxolane-2-yl)
1,2-Cyclohexane dicarboxylic pyridine
anhydride 4,4'-Dithiomorpholine
"Cedrene"* 3,4-Dimethyl furazan
l-Chloronaphthalene Di iso amylamine
2-Chloroquinoline Di butyl amine
3-Cyclohexanepropionic acid o-Diethyl benzene
* Trademark for terpenes obtained from cedarwood oil.
- 46 -
.
,
, ~ ' ' ' , .
~065Z74
HETEROCYCLICS, ACIDS, AMINES (& SALTS),
MISCELLANEOUS SUBSTANCES (cont'd)
3,4-Dimethylpyridine Methoxyacetic acid
Dibutylamine 4-Methyl morpholine
o-Diethylbenzene N-Methyl-p-nitroaniline
l-Ethylnaphthalene N-Methyl-o-nitroaniline
2-Ethylnaphthalene 2-Methyl quinoline
3-Ethylrhodanine 2-Methyl pyridine
l-Ethylpyrrole 3-Methylpyridine
Ethyldiethanolamine 4-Methyldioxolane
o-Ethyltoluene Methyl urethane
Fluorosulfuric acid- ~ -Methyl styrene
antimony pentafluoride l-Nitropropane
Isopentyl nitrite 2-Nitropropane
Heptanoic acid l-Nitrobutane
:- Lactonitrile l-Nitrohexane
. Lithium oleatè, palmitate, Nitro trichloro methane
` stearate n-Octyl nitrate J
o-Iodotoluene 4-Phenyl-1,3-dioxane
p-Isopropyltoluene 3-Propyl rhodanine
: l-Iodonaphthalene Propyl disulfide
l-Iodo octane Propyl sulfide
Iso pentyl nitrite Propyl sulfone
2-Methyl benzothiazole Piperidine
2-Methyl benzoxazole Valeric acid
1,2-methylenedioxybenzene Trimethylene sulfide
l-Methyl naphthalene --
: 2-Methyl naphthalene --
2-Methyl-2 nitropropane --
N-Methyl-N-nitrosoaniline --
: - 47 -
~ '
- - . . .
- ~ ... . : .
' ' ' ,
- 1065Z74
MlSCELLANEOUS SUBSTAN OE S
Acridine red Lutidines
Acridine iso thiocyanate - 2-Methyl-2-thiazoline
Acriflavine o-Methyl toluidine
Aesculin Metrizamide
Allantoin Nile Blue
Aluminum lactate Neutral red
Amino phosphonic acids Neutral violet
;: Bismuth ethyl camphorate Phenyl ethylene oxide
Calciu~ carbamate l-Phenyl propane
Calcium borogluconate Primuline
Calcium palmitate 1,3-Propane sulfone
Calcium stearate Isopropyl benzene :
: Calcium galactogluconate N-Propyl nitrate
bromide 1,4-Pyrone
Circumin Pyru~ic acid
Cinnamonitrile Safranin
;: o-Diacetyl benzene Sulfonyldiacetic acid
- Decahydroquinoline Sulfur iodide :~
: 20 1,4-Dichlor-2-nitro benzene Tetrabutyl ammonium perchlorate
1,2-Dichloro-4-nitro benzene Tetra~utyl ammonium fluoro-
l,l-Diethyl urea borate
Dimethyl phosphite Tetrabutyl ammonium bromide
~; Diphenyl selenide Tetraethyl ammonium perchlorate
Diphenylimidazalone-sulfonated Tetraethyl thiuram sulfide
Flu~resca~ine Tetraethyl ortho silicate
N-Iodoacetyl-N'-~5-sulfo-1- Tetraethyl ortho titanate
.
naphthyl)-ethylene diamine 1,1,3,3-Tetraethyl urea
N-Iodoacetyl-N'-(8-sulfo-1- Tetra isopropyl ortho titanate
` 30 naphthyl)-ethylene diamine 1,1,3,3-Tetraethoxy propane
.. _ . .. ... .
*A dyestuff which is a dieth~l dia~nino phenoxazonium salt.
1065274
NISCELLANEO~S SUBSTANOES (cont'd)
Tetraethyl tin Trimethyl sulfonium iodide
Tetrahydrofurfuryl oxy- Trimethyl sulfoxonium iodide
betra~ydropyran Trimethyl amine N-oxide, hydrate
5 i,2,3,4-Tetrahydro 1,3,~_~dnltro ken~e
isoquinoline 2,4,6-Trimethyl pyridine
2,3,4,5-Tetramethyl pyrrole Trichloromethyl phosphonic acid
N,N,N',N'-Tetramethyl-l, Trioctylphosphine oxide
8-naphthalene diamine Trioctyl phosphine
10 2, 3, 5,6-Tetramethyl piperazine Tri-n-pentyl amine
2,2, 4,4-Tetramethyl-1,3-cyclo- Vasoflavin
butadiamine Vinyl carbazoles ~:
1, 2, 3,4-Tetramethyl benzene Zinc oleate
3, 3 ', 5,5'-Tetramethyl benzidine
Tetranitro methane
Tetracyanoethylene
Thiamorpholine
Thiolactic acid
_ . . . _ . .. . . .. . . . . .
3,3'-'~hiodipropi~nic acid
~ 20 Thiophthene
: 1,4-Thioxane
Thiofla~ine
o,m,p-Toluidine
Triazo benzene
Tri-n-butyl amine
Tri i~ butyl amine
Tri-n-butyl phosphine oxide
Trl butyl phosphine
3,5,5-Trimethyl-2,4-oxazolidine
-30 dione
~ i~.4
. ~,,' .
.: 49.
1065274
As part of the methodology which may be used to
categorize the materials such as those listed herein they may
-- be titrated with distilled water and their conductivities ob-
tained. The dilution/conductivity curve so obtained indicates
the rate of change of conductivity with dilution as well as the
diminishing point or plateau levels of conductivity achieved
within reasonable dilution means which helps characterize the
~; materials as to the several categories discussed herein, such
- as very active solvents, active solvents, etc. The following
data illustrates the applicatlon of this technique (resistances
are given in millions of ohms). The very low plateau of
.. . .
resistance at the indicated dilution levels establishes that
dichloroacetic acid and mercaptoacetic acid are in the category
of very active media. The somewhat higher plateau of ethylene
carbonate and 2,5-hexanedione place them in the category of
active media. By such a method a convenient rating scale can
be established for evaluation of different media. This technique
assists in tailoring media to a desired conductivity value by
observation of resistance values at different levels of dilution.
INITIAL RESIST~NCE RESISTAN OE
RESISTANCE WITH .05 ml. WITH 1 ml.
SAMPLE 0.3 ml. WATER ~DDED WATER ADDED
; ,
dichloroacetic acid 100 0.042 0.001
mercaptoacetic acid 1 0.050 0.004
ethylene carbonate 0.2 0.20 0.065
2,5-hexanedione 7 2.2 0.060
Often even partial miscibility with water is sufficient to
indicate the range of activity or character to be expected.
Further, these studies are extended by titration against
materials other than water. Thus, for example dichloracetic
acid, formamide and thiodiethylene glycol were used. These
50.
.
:
-- 1065Z'74
then represent a different solvent miscibility capability and
profile. Of these agents, the formamide has a very high dielec-
tric constant and greater conductivity than water, whereas the
thiodiethylene glycol's conductivity was in the range of the
water used and also achieved ~he level of conductivity of the
water when a drop of water was added; that is, upon only slight
dilution with the water. The conductivity changes so produced
by dilution with nonaqueous materials were further characterized
by observing changes in plateau levels so produced by addition
of a minor quantity of secondary solvents which may be water.
This helps to relate the influence of secondary solvents such
as the active or very active type (or inert type for suppressant
activity) to the conductivity profile. Such effects are variable
or characteristic for the diluted agents to which the secondary
diluent is added. Further, the conductivity titration curves may
be studied with a particular conductivity-valued diluent which
may already be an ionized or higher conductivity system. For
example, the dilution of hydroxy compounds and ethers with
fairly conductive aqueous ammonium nitrate solution and acetic
acid may be cited. The comparison was made where both latter
systems had equivalent conductivities. Of the compounds 1,3-
butane diol, 2,2-methoxy ethoxy ethanol, 2-oxydiethanol bis
(2-methoxy ethyl) ether, sorbitol ~40% aqueous solution) and
sorbitol (57~ squeou~ solution) by volume, the dilution of the
aforementioned aqueous conductive solutians by the latter com-
pounds generally shows a ~imilar decrease in conductivity over
the titration range although certain definite curve shapes were
derived. Thus, the relative activity and suppressant profile
of the various diluants became evident. ~ith thi~ technique, the
substantial difference with bis (2-methoxy ethyl) ether is
51.
. ~ . .
- ~ ~065Z74
readily evident. Also differences were noted in the effects of
aqueous sorbitol at various concentrations, as compared to the
nonaqueous materials, upon the lonized ammonium nitrate solution
which effects were otherwi~e somewhat less pronounced than upon a
dilute acPtic acid solution. Fur~her, the various systems may
be studied as they affect equilibria characteristics, ionization
and/or formation data for the materials of interest and at
; - various p~' Q . A large compendium or library of data may be
prepared for these variou possibilities in order to achieve
a lessened empirlcal ba~is for conditions of ~ystem selection
- for use. As a re~ult of thi~ invention an already established
broad table i~ given of basic ~olvent systems from which future
; screening can be made to develop media for use with particular
~pecies.
AB illustrated by the above examples and the lists of
chemicals, the proce~s of thi~ invention comprise~ separating or
mobilizing chemical specie~ which ~re conveniently on a support
such as filter paper in a medium of low conductivity across
which a high voltage i~ impressed. The media-baso comprises
one or more compound~, for ex~mple, inorganic or orgnnlc compounds
such as glycols, ether~, e~ter~, dlones, lactone~, amides,
nitrile~, alcohol~ and water. An agent may be added to the
medium to ad~u~t it~ conductlvity and ~uch agent may be sel3cted
from the group con~i~ting of water, acld~, ba~es and salts.
The voltage used ln the procesB i8 withln the rango of about 50
to 25,000 volts/cm. At very high voltages, and particularly
with volatile or gaseou~ ~ubstance~, cooling may be requir~d.
The preferred range i8 about 200 to 3,000 volts/cm, and in this
range the proces~ can be c~rrledout wiff~textern~l cooling.
The conductivity of ~he medium i~ preferably ad~usted ~o provide
52.
1065274
; a current density in the range of about from 0.2 to 100 micro-
; amps/sq. cm. based on the area of, for example, filter paper asa substrate. The preferred range is 1.4 to 54 microamps/sq. cm.
For bulk work and with external cooling, current densities above
i 5 100 microamps/sq. cm. can be used. The transport medium, after
appropriate adju~tment of its conductivity, is subjected to a
sufficiently high voltage at a low current level (at about the
threshold level) to induce separation of the chemical species
therein at a rate of about 1 cm/sec. to about 0.25 cm/min.
In the above examples, at the conditions indicated, no external
cooling was required.
Refinement of the media formulation techniques can lead
to resolution improvement in the separation of given components by
EMP. For example, the media of 5 ml. propanediol cyclic carbon-
~ 15 ate, 5 ml. propylene glycol, 2 ml. N-methylacetamide and 0.4 ml.
- tetrahydrofurfuryl alcohol allows the resolution ~f rhodamine B
and 6G of examples 16 above in considerably less than the 3.6 cm.
required in example 16. The utilization of resolution improve-
ment to ~horten separatlon distances makes it possible to mini-
mize diffusional effects.
It is po~sible to improv2 resolution generally
according to the followlng procedure. ~ suitable ~olvent is
found for the chemical specie~ to be transported. The nature,
of the chemical species to be transported is then analyzed in
terms of its proton donor/acceptor properties. The donor/acceptor
properties of a number of chemical species are catalogued in
the literature. E.g., V. Gutmann, Coordination Chemistry in
Non-Aqueous Solutions (1968). A component should then be added
to the media which will interact in a proton donor/acceptor
interaction with the chemical species. In many instances the
.
.
:, . .~ .:
1065274
proton donor/acceptor properties of chemical species are not
catalogued, or are complex. In such cases it is possible to
determine the type of media components that will improve reso-
lution by testing the system through the simple technique of
addition of a very strong proton donor to one sample and then
~- a very strong proton acceptor to another. If the strong donor
increases the mobility (rate of movement) of the compound, donors
of varying strength are then tested to determine which provides
the greatest improvement in mobility and resolution. An analo-
gous procedure is followed if the strong proton acceptor
increases the mobility rate of the chemical species. ThP addi-
tion of a component which can interact with the chemical species -
to be transported by proton donor/acceptor interaction seems to
facilitate initial mobilization of the chemical species. The
dielectric constant of the media is then adjusted if necessary
to a moderately high level. It may also be necessary to correct
`; for electrical instability of the media by addition of a com-
pensating component as detailed above.
As an additional aspect of this invention it has been
determined that improved tailoring of the semiconductive media
also permits, for certain chemical species, exhibition of an
EMP response observable with the unaided eye at relatively low
voltages and reduced power levels, as compared to the high vol-
tage, high power processes described above. Voltages below
50 v/cm and even less than 20 v/cm on conventional support media
have been utilized. For example, one can achieve EMP transport
at power levels as low as 3xlO 6W. to 1.7xlO 5W. with voltages
of 2 to 4 volts at 1.5 to 4.2 ~A. over several centimeters of
#l "Whatman"* filter paper. This represents EMP operation at
potentials of several millivolts per centimeter at tenths of
*Trademark
- 54 -
~` " 1065Z74 :~:
microwatts per square centimeter. The limit on low voltage
EMP is the level at which electrical diffusivity comes into
play. It has also been found that certain agents will act to
reduce the threshold current of a chemical species.
A media system is modified to allow low voltage EMP
response and to reduce threshold current in much the same
manner as it is modified for resolution improvement. Specifically,
initiators and mobilizers are added. Initiators are compounds
which act to reduce the threshold current of a given chemical
species, and mobilizers are compounds which act to increase the
mobility (transport rate) of a given chemical species. There
is some overlap between the classes of compounds useful as ini-
tiators and those useful as mobilizers, that is, some compounds
will act both as initiators and as mobilizers. -
In general, materials which will interact on a proton
donor/acceptor level with the chemical species to be transported
and high dielectric constant materials are useful as initiators
and mobilizers. Examples of compounds which are often useful ;-
both as initiators and mobilizers are N-methylacetamide and sali-
cylaldehyde.
With the use of initiators, threshold currents may
be adjusted to as low as 0.2 to 0.002 ~ /cm , and EMP may be
carried out at these currents at slower but still effective
mobility rates with voltages as low as 0.05 to lOv/cm. The
. .
voltage level of 0.05 v/cm xepresented a practical minimum
during experimentation because voltage effects on this order
inherent to the system were encountered. Overall, considering
both high voltage and low voltage EMP, the EMæ voltage range
may be 0.05 to 25,000 v/cm, with power levels as low as
_9 2
1.2xlO to 5xlO~5W/cm .
,', ~ ' '
. :
- :
' :
55.
- . .
~065Z74
.
The following examples illustrate the manner in which
media, suitable for EMP transport according to the criteria of
semiconductivity and compatability with chemical species des-
cribed in connection with high voltage EMP above, are modified
with initiators to reduce threshold current.
EXAMPLE SOLVENT FORMULAE
22 7 ml. propylene glycol, 3 ml.
diacetone alcohol (mobilizer,
also enhances resolution), 2.2
ml. N-methylacetamide (high ~ ;
dielectric constant material~
acts as initiator and mobilizer),
1.3 ml. formamide (same).
23 21 ml. propanediolcyclic carbonate,
9 ml. methoxyethyl ethanol, 12 ml.
tetrahydrofurfuryl alcohol, 3 drops
HNO3 diluted 1:3 with water.
,
,:
The media of example 22 above has been used to sepa-
rate rhodamine dyes, and also to separate vitamin B12 and
sodium riboflavin phosphate mixtures.
,. .~
j ~ The media of example 23 was used to separate rhodamine
B and 6G in less than 0.5 cm. The tetrahydrofurfuryl alcohol
acted to enhance the mobilization of the compounds magnifying
molecular differences. Without this component the two species
showed almost equivalent motion over several centimeters.
As further examples, the media of example 23 can be
altered to increase its conductivity by the dropwise addition
of conductivity, initiator or mobilizing agents (A.) to obtain
the electrical values (B.) and power levels (C.) set forth in
the table below.
- 56 -
- ..
1065Z74
(B.) Electrical Values (C.) Total EMP Power
-- for EMP run (on Level In
(A.) Agent 4 x 1 cm Filter Paper) Microwatts
Nitric acid (1:30 in water) 4V, 4.2 ~a 17
Ammonium Bromide lOV, 1.2 ~a 11
(Sat'd. in glycol)
formamide lOV, 1.2 ~a 12
N-Methyl Acetamide 20V, 2. ~a 40
N-Methyl formamide lOV, 4.1 ~a 40
Hexamethyl phosphoric triamide lOV, 3.5 ~a 35
,
-~ The accomplishment of EMP at low voltages with accom-
panying low power levels has important ramifications in that EMP
under such conditions would be compatible with living organisms.
Voltage, power and threshold current levels appropriate for low
voltage EMP exist in living organisms and consequently are clearly
; tolerated by them. Thus the EMP techni~ue of formulation of
semiconductive media may be effected within a living organism to
control or study chemical substances in physiologically functional
systems.
The voltage necessary to the EMP process may be supplied
by potential differences existing naturally in an organism and
merely applied to the appropriate site, or may be imposed from an
` outside source.
. .
` It is well known and recognized in the prior art that
potential differences exist within living organisms naturally.
Also, in connection with the experimentation leading up to the
present invention, it was found that a voltage reading on the
order of tenths of volts or millivolts with a current of microamps ~ -
or slightly less was generated across the phase boundary between
two immiscible or partially immiscible liquids in certain instances.
- 57 -
.
: ^:
10652~
Not all phase boundaries produced this junction effect; for -
liquids, partial solubility in each other seems to correlate
with the effect to some extent. The junction effect may be
modified by use of a permeable membrane between the phases.
Propanediolcyclic carbonate and water form different phases and
exhibit this junction effect. It is believed that juxtaposition
of liquids in the cells of living organisms could give rise to a
liquid junction effect providing sufficient voltage for the
effectuation of EMP. Such effects appear to be amenable to
, 10 modification by EMP media formulation techniques.
The process of EMP media formulation may be carried
; out in conjunction with an externally applied voltage, as well
as with one existing naturally within an organism or portion
i~ thereof, to effect an EMP response. Some evidence already
exists, for example, of improved bone and other tissue healing
or growth in the presence of an applied voltage. See Lavine
et al., Electric Enhancement of Bone Healing, 17 Science 1118
(March 1972). Such effects could be enhanced by application of
the desired chemical species. For example, the initiators or
dielectric constant modifiers for transport of biochemical
species described herein could be applied to facilitate or en-
hance an electrophysiological response such as transport or
orientation of the appropriate materials across a bone break.
More generally, given voltages and current levels
- within living organisms, the procedure of media formulation of
the present invention could be used to construct or modify
within the organism appropriate semiconductive media for en-
` - hanced transport of physiologically significant chemical species.
For example, EMP media formulation techniques could be used to
speed reparative or other chemical species to injured portions
of the body. EMP media formulation might also be useful
- 58 -
~ .
` `
,` 1065Z7~
with respect to the application or retention of drugs. EMP
might be used to effect or control natural processes on a humo- -
ral, intercellular, or even intracellular level.
-~; In the preparation of media within an organism, toxi-
city of the media components and other aspects of compatability
with the physiological system would be of key importance. Con-
siderations of toxicity would include considerations of irrita-
tional, inhibiting and denaturing characteristics. In selecting
chemical materials useful for in vivo EMP work, the particular
tissue or function to be modified must be taken into account.
Even nitriles can find utility in such work, e.g., 2-cyanoethanol
is relatively non-toxic as well as non-irritating and non-absorbing
dermally.
As an example, if it were desired to utilize an agent
intravenously in mammals (including humans) which is well toler-
~: .
ated in fair concentrations, and which should contribute amidebut not urea character, either lactamide or nicotinamide may be
selected. For liquid or low melting N-alkylamides or N,N-dialkyl
amides, often of high to very high dielectric constant, analogues
- 20 such as N-ethyl nicotinamide or N,N-diethylnicotinamide may be
considered. A number of related compounds, e.g., dibutyl forma-
. .,
mide, N-cyclohexyl-formamide, diethyl nipecotamide, or N-(2-hy-
droxyethyl) lactamide, might be useful.
In addition to these examples, a listing of agents is
given for use in formulating buffers with minimal impairment of
sensitive biological systems. Also, a brief listing is given of
.
other representative agents sufficiently tolerated to be generally
useful for biological work. Additional criteria for this latter
group include low melting point, good liquidity range, water
solubility, other solubility, solvent activity, inertness or
- functionality, etc.
; - 59 -
.~'
. .. . : - .: . ~, - , ,
``' 106527~
TABLE IV
Biologically Compatible Buffer Agents and Zwitterionic Buffers
cyclohexyl aminoethane sulfonic
acid
cyclohexyl aminopropane sulfonic
acld
N,N-bis (2-hydroxy ethyl
glycine)
N'-2-hydroxy ethyl piperazine-
N'-2-ethane sulfonic acid
N'-2-hydroxy ethyl piperazine-
N'-2-propane sulfonic acid
imidazole
2-N-(morpholino) ethane sulfonic
acid
morpholino propane sulfonic acid
piperazine-N,N'-bis (2-ethane
sulfonic acid
N-tris (hydroxy methyl)
methyl glycine
N-tris (hydroxy methyl) methyl-2-
aminoethane ~ulfonic acid
tris (hydroxy methyl) methyl
aminopropane sulfonic acid
; 25
., .
.
- ' ~
`. 30
.
. .
:~ ~ 60.
. ~ , . . .
. , . -~ . ~ .
.
-`` 1065Z7~
TABLE V
Other Repre~entative Materials Suited for
Use In EMP Media In Biolo~ical Systems
~-acetamidocaproic acid farnesol
: 5 L- ~-acetamido-~-mercaptopro- fructose
pionic acid D-gluconic acidGf-lactone
acetamido phenol glutathione
acetanilide glycerosphosphoric acid
allantoin 2,6,10,15,19,23-hexamethyl
10 allantolactone tetracosane
allyl-2,5-dlmethyl-3,4- ~-hydroxy-2-butanone
. methylene dioxybenzene 2-hydroxybenzyi phosphinic
n-amyl butyrate acid
: anhydrom~thylene citric acid N-(2-hydroxyethyl)palmitamide
D-L-arabinose 5-hydroxy-2-hexenoic acid
arabitol lactone
. _
: .arachidonic acid
2,6,10,15,19,23-hexamethyl-
benzyl acetate 2,6,10,14,18,22-tetra-
~: 1,3-bi~ ~hydroxy methyl) urea cosahexene
. 0 bis (2-ethylhexyl) 2-ethyl- 15-hydroxy pentadecanoic acid
: ~ hexylphosphonate E-lactone
ethoxy (10-20) glucose 5-hydroxy-2 ~hydroxy methyl)-
ethyl linoleate 4-pyrone
ethyl le~ulinate 3-hydroxytrimethyl-3,7,11-dodecanoic
i 3-ethyl-1-hexanol acid
2-ethyl-2-methyl succinimide "Ichthymall"*
2-ethyl ~ulfonyl ethanol i~oaAcorbic acid
ethylene glycol diacetate iso-eugenol
l-ethynyl cyclohexanol inositol hexaphosphoric acid
) eugenol isopropyl myristate
., :
61.
* Trademark for ichthanmol (ammonium ichthosulfonate).
-0:
- :
- :
`` 106SZ74
iso-valeric acid 2-(Chlorophenyl)-3-methyl-2,
isovaleramide 3-butanediol
kojic acid cineole
lactobionic acid citric acid
linoleic acid ~ cyclopentamethylene-
lipoic acid tetrazole
methylal acetamide Diethyl ethylphosphonate
methylnicotinate N,N-diethyl iso valeramide
~-Methyl-~,~-crotonolactone N,N-diethyl-m-toluamide
N-methyl pyrrolidinone 2,2-dimethyl-1,3-dioxolane-
~.
l-methoxy-4-propenyl benzene 4-methanol
p-methoxy benzaldehyde 2,6-dimethyl-m-dioxan-4-ol
p-methoxy benzyl alcohol acetate
myristyl alcohol dimethyl polysiloxane
3,4-(Methylene dioxy) benz- 2,3-epoxy-2-ethyl hexanamide
aldehyde eicosamethylnonasiloxane
nicotinamide ascorbate ethyl phenyl ether
nicotinic acid monoethanol- o-ethoxybenzamide
. amine propoxy (10-20) glucose `
- 20 2-nitro-2-propyl-1, 3-propanediol P~ntaerythritol chloral
octanoic acid pentaerythritol tetraacetate
oleic acid 3-pentanone
.. oils, natural 3-phenoxyl-1,2-propanediol
orotic acid phenoxyacetic acid ~;
: N-(pantothenyl)-~-amino- polyolyethylene (20) sorbitan
ethanethiol monooleate
Pantothenic acid phenylbutyramide,~-2-phenyl-2-
cocoa butter hydroxy propionamide
-caprolactam 2-phenyl-6-chlorophenol
choline salts piperidinium salts
- 62 -
::
`` . 1065274
poly(ethylene glycol)-p- theophylline & salts
nonyl phenyl ether o-thiocresol
polyoxyethylene stearate thujic acid
polyvinyl alcohol tiglic amide
polyvinyl pyrrolidone tocopherols, tocols
N-polyoxyathylene fatty acid 2,2,2-trichloroethanol
amides triethylene glycol
6-propylpiperonyl butyl diethyl- 3,5,5-trimethyl-2,4-
: ene glycol ether oxadolidinedione
3-pyridine ethanol undecylenic acid
pyrrolidinone, 2- veratrole
polyethylene glycol-p-iso viologens
octyl phenyl ether . vital stains
steroids, natural and derived, valerolactone
lS e.g., ex-lanolin vitamins K, A, ~ derivatives
salicylamide wetting agents
sorbic acid
-tannins
. cis-terpinhydrate
; 20 tetrahydro-3-furanol
: tetrahydrofurfuryl alcohol poly-
~ ethylene glycol
3,7,11,15-tetramethyl-2-
hexadien-l-ol
; 25 2,6,10,14-tetramethylpen- -
~ tadecane
`~ tetraethylene glycol dimethyl
ether
thiamine, salts & derivative~
: 30
~ : 63.
:106527~
EMP media components may be applied to an organism
through known techniques, including injection and local profusion.
EMP in living organisms or in tissues may be operated
at threshold currents on the order of 0.002 ~A/cm or higher,
- at voltages of 0.3 v/cm or higher. If slower EMP response is
acceptable for a particular use, thresholds of 0.0005 ~A/cm may
be utilized with voltages as low as 0.05 v/cm.
Related to the use of EMP in biological systems is the
use of EMP to mobilize biochemical species including high thres-
hold ones as proteins-globulins, enzymes, polypeptides, nucleic
acids, steroids, lipids, lipoproteins and fatty acids. Proteins
and other biochemical compounds are susceptible to thermal and
; chemical degradation, and are commonly handled in aqueous solu-
tion, often in chilled buffered electrolyte solution. However,
water as a major component in EMP media has the disadvantages of
forming electrolytic solutions and of being rather evaporative.
Thus special attention has been given to the adaptation of high
water content systems to EMP usage, and also to the application
of EMP to proteins and related substances in nonaqueous systems.
Since the activity of biochemical compounds is linked to their
. . .
structural integrity and sensitivity, an additional aim has
been formulation of a versatile set of media which preserve this
activity.
The general technique for formulation of an aqueous
EMP media for protein transport involves reducing the conductivity
of water by addition of a suppressant, adjusting the dielectric
constant by addition of a high dielectric constant material if
necessary, and adding initiators and/or mobilizers to beneficiate
the movement of the proteins.
As disclosed above, it has been found that a number of
compounds will suppress the conductivity of water to varying
- 64 -
.
- 106S;Z74
extents, thereby alleviating the problem of high conductivity
in aqueous media. These compounds also function as miscible
protein solvents. The conductivity suppression results are set
out in the form of an example below.
EXAMPLE 24
Various protein-compatible solvents were combined with
water (volume ratio = 16/9). Pure solvents were used when possi-
ble, as the trace contaminants in commercially available materials
can affect conductivity suppression. (This is illustrated by the
values given for compounds (7) and (18) below which are the same
substance obtained from two different sources.) Relative values
of conductivity suppression as compared to the conductivity of
water were:
(1) thiodiethylene glycol 2.2
(2) 2,6-dimethyl morpholine 2.6
(3) methoxy ethoxy ethanol 2.6
(4) 2-pyrrolidone 2.7
More strongly conductivity suppressing compounds are:
! , :
(5) ~-butyrolactone 3.3
. .
'~ 20 (6) sorbitol 3.8
:
(7) 1,3-butanediol 3.6
(8) propylene glyco] 3.6
; (9) dimethyl formamide 3.6
A ~roup of increased strength suppressants are:
(10) dimethyl acetamide 4.8
(11) tetrahydrofurfuryl alcohol 4.6
(12) butoxy ethoxy propanol 5.0
(13) 6-hexanolactone 5.0
(14) oxydiethanol 5.4
(15) diacetin 5.6
- 65 -
.' ' .
~ `
-` ` 1065Z74
The truly potent class of suppressantsfor water may be repre-
sented by:
(16) 2-[2-~ethoxy ethoxy) ethoxy] ethanol 8.3
- (17) 1-[~2-(2-methoxy-1-methyl ethoxy)l
-l-methyl ~thoxy]-2-propanol 10
(18) 1,3 butylene glycol 12
Selection of a suitable suppressant solvent should take
into account the effect of the suppressant on protein migration.
Thus compounds (10), (11) and (13) above may beneficiate protein
mobility, whereas (3), (4), (9), (14) and (18) may be less potent
in this regard. -
~ Additional solvents for biochemical compounds include
;; alcohols such as methyl "Carbitol", phosphonates such as diethyl
ethyl phosphonate, lactones such as 6-hexanol~ctone and sugars.
Solvent compatability with the substrate is another
consideration. With improper solvent selection, the solvent may
attack the substrate resulting in altered porosity, structure ;~
collapse or similar effects. Proper solvent selection in media --
formulation permits use, for example, of ion-exchange of "thin-
layer" plates, as well as cellulose derivative films such as the
` nitrate or acetate, or agarose, acrylamide or silica gels impreg-
nated with EMP media.
The excessive use of potent suppressants may result
in a system with internal resistance so high that substantial
resistive heating results, especially where high threshold current
operation i8 indicated. Thus, selection of the less potent sup-
pressants is often satisfactory. The Tc requirements of proteins
and related ~ubstances are often in the range of 4.6 ma/50 cm2 or
more on a cellulose substrate as opposed to 1.2 ma/50 cm2 or
less for most other compounds.
:, :
~ -- 66.
- : . :
- : ., . :.: .. : . -
` - ` 1065Z'74
- Reducing the water content of EMP media as described
above may alter the dielectric constant of the media. This
change may be offset, with resulting re-establishment of the
high dielectric constant desirable for EMæ, by addition generally
of very high dielectric constant components. Examples of suit-
able materials for this dielectric constant adjustment include
hydroxy ethyl formamide, N-methyl formamide, formamide, N-methyl
acetamide and related compounds. Generally, N-alkyl and N-aryl
; amides are useful. Often these compounds, especially when of
only commercial purity, will tend to increase the conductivity
of the media, thereby opposing the suppressant mechanism. Such
conductivity contribution may be used to compensate for an overly
high internal resistance caused by a strong suppressant.
; High threshold values of biochemical species may be
'' 15 advantageously reduced, and the mobility of the speciee in EMP
increased, by the use of initiators and mobilizers. Many proteins
` were found to be particularly susceptible to the influence of pro-
-~ ton acceptor substances in increasing mobility, but were relative-
ly ind$fferent to mobilization by proton donor molecules. Initi-
~20 ator substances, though in relatively low concentration, contri-
bute substantially to the lowering of threshold current, and if
`` they also act as mobilizer~, to the enhancement of species mobili-
ty. For proteins, initiators may be used to bring threshold levels
down from 4.6 ma/50 cm to 3.4 to 1.0 ma/50 cm2 ~20~A/cm ) with
voltages in the 50 to 25,000 v/cm range. Typical initiator sub-
stances, mobilizers, and worthwhile solvents are: nitrobutanol;
3-acetyl 3-chloropropyl acetate; salicylaldehyde; N-methyl-acetamide;
boric acid; phenols; guaiacol; fumaric and barbituric acids; piper-
~; azine; furfural; tributoxy ethylphosphate; ~ trichloro-t-
butyl alcohol; dimethyl-l, 3-dioxolane-4-methanol; 2-ethyl sulfonyl
`:
,'~' ,
,
. 67.
;~ . .
1065Z74
ethanol; tetrahydrofurfuryl alcohol; N-substituted pyrollidones;
dimethyl sulfoxide; 2,2-oxydiethanol; ethylene cyclic carbonate; `
tetramethyl urea; thiodiethylene glycol; l-ethynyl cyclohexanol;
tetrahydro-3 furano,2,6-dimethyl-m-dioxan-4-ol acetate; and
2,5-bis (hydroxy methyl) tetrahydro furan, other amides, parti-
cularly N-alkyl and dialkyl and hydroxy amides, other proton
acceptors and buffer systems. Very often high dielectric cons-
tant substances will act as mobilizers or initiators.
. .
Electrophoresis of proteins is often done in high pH
(alkaline) buffer because of the dependence in electrophoresis
on isoelectric points. In contrast, EMP transport of proteins -~
may be carried out in acid media. Buffers may be prepared from
the list of biologically compatible agents given above, or may
be of the more commonly used Tris, Veronal or Sorensen types.
In addition, more common organic acids and bases may be used.
Examples of acid buffers useful for EMP transport of proteins
and related substances are:
; tetramethyl ammonium hydroxide/acetic acid
triethylene tetramine/2,2-oxydiacetic acid
dimethyl amine/picric acid
diethanolamine/dichloracetic acid
triethanolamine/dichloracetic acid
piperazine/dichloracetic acid
Media prepared as described above, with combination of
water, one or more suppressants, one or more agents for increasing
the dielectric constant, and one or more initiators (and/or mobi-
iizers) may effect separation of proteins within a minute or so
in a few centimeters of "Whatman"* #1 filter paper, while the
same separation on the same substrate would take up to 16 hours
over as much as 15 cm. of substrate with electrophoresis.
*Trademark - 68 -
.
`- 1065274
A number of proteins and related substances are
insoluble in water. For example, some derived or conjugated~
; proteins, as well as some polypeptides, keratins and prolamines,
are water insoluble. While this problem may be overcome in some
s instances, as with zein (prolamine) by use of the modified
aqueous media described above, the use of nona~ueous media pro-
vides additional flexibility.
An alternative to aqueous EMP systems for proteins
and other biochemical compounds is the use of other solvents
analogous to water in proton donor number (DN=18.0 for water)
and dielectric constant (DC=81.0 for water). Especially useful
are ethylene cyclic carbonate (DN=16.4, DC=89.1, boiling point
~- (BP) =245C) and propanediol-l, 2-carbonate (DN=15.1, DC=~9.0,- - BP=240C). These solvents contribute superior heat stability
to the media formulation, permitting operation with greater re-
sistivity and hlgher ~ltage gradients without need for ex~x~l cooling.
- Certain solvents show amore intense solvent action
than does water for some proteins. Thus, keratins which are
water insoluble may be dissolved in other solvents such as
dimethyl sulfoxide. Prolamines may be solubilized in glycols,
; glycol ethers, and certain alcohols.
Solvents of moderate to strong proton acdeptor proper-
ties are suitable for protein solubilization, and may even form
the basis of the media. Solvents of this type include iodine
monochloride, sulfur dioxide and hydrogen fluoride. For example
anhydrous hydrogen fluoride is a good solvent for fibrous proteins
normally insoluble in water. The collagenous substances, as well
as elastins and reticulins are particularly resistant to solu-
bilization in aqueous media, whereas they are soluble in non-
a~ueous media.
:
~ 69.
," .
`` 1065274
The media for EMP transport of proteins may include
other protein solvents chosen to provide particular properties
such as glycols, amides, ethers, pyrrolidones, lactones, sulf-
oxides, phenols, alcohols and phosphonates.
Suitable aqueous systems for the transport of proteins
in accordance with the foregoing ~able of suppressants using a
solvent/water volume ratio of 16/9 are:
16 ml. thiodiethylene glycol
9 ml. water
2 drops ethanolamine
(separation of protein mixtures including
cytochrome C and myoglobin - electrical
characteristic of 1.8 Kv/1.2 ma)
16 ml. 6-hexanolactone
9 ml. water
3 drops ethanolamine
(gave protein movement and resolution -
electrical characteristic of 1 Kv~1.2 ma)
16 ml. dimethyl acetamide
9 ml. H2O
4 drops ethanolamine
(separation of proteins -
electrical characteristic of 1.6 Kv/1.2 ma)
The following thre~ examples illustrate nonaqueous
media repre~entative of those which have been used for EMP trans-
port of human and bovine albumin, hemoglobin, cytochrome C,
(an enzyme), myoglobin (muscle protein) and pancreatin. In addi-
tion, protein~ have been separated from whole blood in experi-
70.
1065Z74
ments in which the cell debris remained at the origin. Phenol
was a useful media component in these last separations.
EXAMPLE 25
12 ml. - ethylene cyclic carbonate
6 ml. - ethoxyethoxy ethanol
6 ml. - thiodiethylene glycol
6 drops tris-dichloracetic acid buffer
EXAMPLE 26
7 ml. - ethylene cyclic carbonate
7 ml. - ethoxy e~hoxy ethanol
9 ml. - oxydiacetic acid
1.5 ml. - formamide
6 drops triq-dichloracetic acid buffer
`:
':
,~. .
~ 30
~.065Z74
EXAMPLE 27
10 ml. - ethylene cyclic carbona~e
4 ml. - N-methyl pyrrolidone
3 ml. - furfuryl alcohol
s 2.5 gm. - boric acid
4 ml. - 1,3-butylene glycol
16 drop~ piperazine-dichloracetic acid buffer (pH 3. 7)
Acridine orange (fluorescent and indicator)
The following example illustra~es EMP media and
0 electrical conditlons used for the ~eparation of albumins and
e~pecially globulin~.
- ELECTRICAL
CHARACTERISTICS
EXAMPLE SOLVENT FORMULAE ~Stabilized?
28 10ml. ethylene cyclic carbonate 5.2 KV/2.0-3.6ma
4 ml. butylene glycol, 4 ml. "Whatman" ~1
methyl pyrrolidinone, 2 ml. ~10 cm.)
formamide (in~tiator), 2.5g
boric acid, 3 ml.
; furfural tpH buffer and
mobilizer), 16 drops piperazine
dichloracetic acid buffer pH 3.7
- (pH buffer and mobilizer), acridine
yellow tfluorescent indicator)
: .
C The ~ame media was used to separate cytochrome C,
hemoglobin, myoglobin, al~umin, yohimbine, and atropine under
the following condltions:
ELECTRICAL
CHARACTERISTICS
EXAMPLE SOLVENT FO~MULAE tStabilized) _
29 10 ml. ethylene cyclic carbonate, 4.4 KV/3.6ma;
4 ml. butylene glycol, 4 ml. 2.2 KV/1.2ma
methyl pyrrolidlnone, 2 ml. "Whatman" #3
formamlde tinltiator), 2.5 g
` boric acid, 3 ml. furfural
tpH ~uffer and mobilizer),
16 drops piperazlne dichloracetic
acid buffer pH 3.7 tpH buffer and
mobllizer), acridine yellow tfluor-
e~cent indic~tor)
o
-
1065Z74
The use of dyes which act as tracers may be desirable
in some cases to visually follow the separation of colorless
biochemical species. See examples 27-29 above. It must be -
established that the particular dye does not interfere with the -
resolution process itself. Bromphenol blue has been commonly
used with serum proteins, but may migrate separately from the
protein in EMP. For redox sensitive materials, methylene blue
is often suitable, and glutathione either in oxidi3ed or reduced
form may be used to buffer against redox reactions. Safranine-
type dyes bind to and alter the solubility characteristics of
proteolytic enzymes and can therefore by useful in separating
them from other materials. A few milligrams of an easily coupled
fluorescent tracer such as acridine orange will allow visual
observation of many substances including proteins under ultra-
violet light without altering their migration characteristics.
Other tracers such as brightening agents, fluorescent coupling
agents, and even fluorescent antibody material may be useful in
following protein transport. Additional tracer agents for bio-
chemical and other work are vital dyes such as the flavines and
. ~. .
primulin. Nile blue may be especially useful alone or in combi-
nation with other dyes under U.V. and daylight. Neutral red
with aesculin remains sensitive at about 1000x dilution with
daylight alone. The U.V. dyes are also convenient for locali-
zing weak positive or negative charges in biological structures.
Antibodies or other coupling tracer materials as well as radio-
active derivatives can also be useful, e.g., rhodamine B-isothio-
cyanate; fluorescein isothiocyanate; p-isothiocyanato acridine;
4-chloro methyl-l-acridine; 1-ethyl-2-[-3-(1-ethyl naphthol [1,
25] - thiazolin-2-ylidine)-2-methyl propenyl]-naphth [1,2]
thiazolium bromide. Additional possible tracers are phenazine
methosulfate,
- 73 -
1065274
Remazol brilliant blue R, thiazolyte blue, protoporphyrin IX,
citrazinic acid, quinine, lisamine, rhodamines, Cleve's acid
and umbelliferone.
Another aspect of the present invention is the use of
S the technique of EMP media formulation to fabricate gaseous
semiconductive media which will allow controlled conduction
without need ~or evacuation, very high temperatures, or very
high voltages. The application of the techniques of formulation
of liquid EMP media to gaseous media formulation led to the
achievement of high levels of conductivity without the need
for high potential. The aim in construction of a gaseous EMP
media is to increase the conductivity level of the gas to the
level of semico~ductivity or other level convenient for the
desired application.
Industry has made use of gases largely as insuiators.
Most gaseous conduction performed currently focuses on the high
dielectric characteristics of gases generally. The conduction
commonly takes place wlthin an envelope or other controlled
environment in a relative vacuum with the use of an energy source
(such as a thermoelectric filament) to control conduction. In
such devices the presence of materials of lesser dielectric
character iB deleterious. Gaseous conductivity i~ also of
;~ importance currently in the area of ionization or the plasma
state. Attempts have been made to produce electricity through
the motion of conductive gases relative to a magnetic field
- (magnetogasdynamics) but it has been found necessary to employ
temperatures 80 high that corrosion of the containers resulted.
It is now possible to achieve conductive gases at or near room
temperature through the use of EMP, and thereby may be possible
to provide a practical means for producing electricity.
; 74.
.' '
.,~ . .
-.
~a~
: ~ :
1065Z74
Formulation of gaseous EMP media provides a useful
scientific technique for investigating the molecular characteris-
tics of materials. In addition, it may be employed in the con-
struction of controlled gaseous conduction devices used for
wireless transmission te.g., in coilless transformer cores),
in light emission studies, gaseous charge transport, gaseous
molecular transport, electrically mediated ga~eous diffusion,
and low potential spar~ gap devices. EMæ media formulation
may be employed to modify fuel combustion systems and the fuel
itself in c~mbustion engines so as to extend the spark propa-
gation distance (e.g., allow separation of the spark plug
electrodes by larger distances thus relying less on explosive
propagation).
Similar principles to those applied in preparation
of liquid semiconductive EMP media are applied in the preparation
of gaseous semiconductive EMP media. Media containing a number
of components, such as three- and four-way systems, are necessary
to effect a substantial alteration in conductivity of the gas
; to bring it into the semiconductive range. Agent~ which acting
together facilitate proton donor/acceptor interaction,
increased conductivity and enhanced dielectric constant are
indicated.
For example, water acts by hydrogen bonding in the
vapor phase as both a donor and acceptor molecule, interacting
with proton donors ranging from strong acids to alkanols ~e.g.,
1,1,1,3,3,3,-hexafluoropropan-2-ol) and with acceptors such as
amines (including pyridines), ethers, alcohols and ketones.
In general, the more conductive or active EMP solvents have been
found particularly suited to gaseous conduction. (See the list
of active agents above.) Also, comixing of materials helps to
75.
: , ........... . .
-. :. . . - . ~ .
10~SZ74
effect enhanced conductivity.
' For example, placing a few drops of triethylene tetra-
' mine in the base of a glass test tube'seated in a mildly heated
sand hath reduced the resistance between the electrodes located
0.5 cm apart and 2.5 cm. from the bottom of the tube to 106 ohms
' from more than 109 ohms in air. The addition of a small crystal
of iodine reduced the resistance to less than 8 x 105 ohms.
Addition of formamide instead of iodine gave 1.5 x 106 ohms,
and the two together reduced the resistance to less than 5 x 105
ohms. With some media, resistances in the hundreds'of ohms were
obtained at low voltages (5-lOv) near room temperature and
; atmospheric pressure.
' As a further example, in ~uch a cell, at a five volt
'" potential, a media was formulated from agents (A.) added stepwise
; 15 'by measuring the resistance (B.) obtained after each step in
' the sequence of addition (C.)
(A.) Agent (B.) Resistance in Cell (C.) Seq~ence of Addition
C~ative
Amount AmDunt in
; Ad d Mixture
' 20 ~etra methyl urea o~ ~100 meg ohms) 5 pts 5 pts
+ N~metbyl acetamide 1.70 meg J~- 1.5 pts 6.5 pts
+ I2 75 K -~ 1 pts 7.5 pts
'' + diethylamine 18 K _rL- 1.5 pts 9 pts
Agents which are useful to formulate gaseous EMP Media
' 25 include iodine, other halogens, amines, volatile salts, amides,
nitro derivatives including nitrosylchloride, acid chlorides,
hydrazine, oxyhalides, sulfur dioxide, hydrogen fluoride, ammonia
or other potent proton donor or acceptor moleculeq, combinations '
thereof, and substances liberating such. Semiconductive media
; '30 formulated from such components ~ccord~ng to the principles of
76.
,. .
' ~ ~
' . - ~ - - ~ -
~` \
1065274
liquid media formulation as modified above provide a controllable
conductive gaseous environment even at atmospheric pressure in
air. The use of high boiling chemicals as classified for liquid
EMP media use requires an elevated temperature to produce the
gaseous EMP effect. Use of lower boiling solvents is therefore
advantageous in the preparation of gaseous EMP media.
Gaseous EMP media may be subjected to voltages of, for
example, 0.5 to 30,000 v/cm, with continuous conduction (rather
than sparking) resulting. Modifying agents may be included in
the media so as to make it susceptible to arc over in the range ;
of 50 to 30,000 v/cm and therefore useful in fuel systems so as -~
to modify or extend the spark propagation properties and/or
electrothermal vaporization prior to ignition.
A further aspect of the present invention is the prac-
tice of EMP within a gel. The gel consistency may range from
fluid to rigid. Gels generally are susceptible to resistance
..:
j adjustment by addition of a small amount of conductivity agent
with a material of high dielectric constant such as formamide or
another amide or alkylamide derivative and a coupling solvent if
necessary to improve miscibility. The EMP media may be washed
into the gel or the gel fabricated with the media in it. One
difficulty with the use of gels as EMP media is that by products
left over from the gel formation process must be removed if they
interfere with the EMP conductivity adjustment and transport.
,: .
Agar gel, polyvinyl alcohol (PVA), silica gel, starch
gel, "Carbopol"* (carboxypolymethylene) and "Crash Safe Aviation
Jet Fuel" (additive-modified kerosene) are examples of gels
which function as EMP media when doped with the appropriate
conductivity-modifying agents in accordance with the principles
described above. Acrylamides could also be employed. An
* Trademark for a vinyl polymer having active carboxyl groups,
used as a thickening or dispersing agent.
77 ~ -
.
' : : -
- : , . .
,
.- . - ~ - .
1065Z74
example of a gel fabricated with an EMP sol~ent within it is
PVA gelled with tetrahydrofurfuryl alcohol. Tetraethyl ortho
silicate which gives a clear glass-like gel with numerous organic
gels permits compatability with various organic EMP media.
Gelatin also provides a clear gel ba e. Examples of chemical
- species which may be transported in such gels include dye
molecules, and even particulate matter may be moved ~t fast
~ates in a "fluid" gel such as crash Qafe aviation fuel.
Voltage and current levels are adju~ted just as in
O cellulo~e supported EMP. A slightly higher current, than
1.2 ma/50 cm2 can also be used for thi~ slabs of gel (to 1/8").
Otherwise, gels 3/8" to 1/2" thick or greater require careful
current consideration to avoid excessive heat buildup.
In EMP separ~tion processes, gel3 are capable of
~5 providing enhanced re olution because of their fine pore
~- structure. EMP induced mov~ment of dye molecules within a gel
may be used as an analytical techni~ue to study the structure and
properties of the gel ~t~elf.
~ he apparatus used for gel EMæ differed from that used
for liquid EMP in that the filter paper ~ubstrate was replaced
with the gel.
EMP within a gel i9 illustrated by the examples below.
EXAMPLE SOLVENT FORMULAE
. .
glycol, ammonium bromide ~to form a saturated
~olution in N-methyl pyrrolidone), and
formamide O
31 5~ welght/volume ceresin or microwax in 20~
sr 30~ xylene plus EMP media components appro-
prlate for use with xylenQ.
The EMP media components referred to in Example 31 may
be the four-way system descrlbed at page 12 or ammonium bromide
) in methoxy ethoxy ethanol, 2(2-ethoxy ethoxy) ethanol, dimethyl
:
r; 7 8 ~
~ .
10~i5274
formamide, dimethylacetamide, dimethyl sulfoxide, n-butanol, or
N-methyl pyrrolidinone.
EMP is susceptible of application to a wide variety
of uses, a number of which have been detailed above. The appli-
cation of EMP to several specialized areas will be urther des- -
cribed here.
EMP may be used in conjunction with media phase
control to provide an information storage, processing and dis-
play mechanism. For example, a medium may be used which is solid
at ambient temperature, which melts or at least increases in
fluidity when warmed. Dye molecules or other detectable or ;~
traceable materials in the media may be transported by applica-
tion of a potential difference when the media is fluid, and
stored with display capabilities when the media is rendered non- -
fluid. The system is non-volatile; the resolidification curtails
diffusionary information loss, and the positioning of the dye
spots in the solidified media provides for information storage.
Gel or porous media might also be used for information storage
and display. A permeable solid support substrate may be incor-
porated in the system to minimize thermal diffusion. By use of
a transparent substrate with refractive index approximating
that of the liquid media, additional clarity can be achieved.
Parallel capillaries, e.g. of glass, may be used to limit dif-
fusion and fix the geometry of the system. Transparent electrodes
(e.g., NESA glass) may be used for display purposes.
EMP is particularly suited for this application in a
number of respects. The high response speed o~ EMP systems would
allow, for example, response times of less than a secondwith a
10 cm/min transport rate between parallel plate electrodes 1 mm
apart. In addition, different threshold currents may be used to
79.
: . - .
:: : , : , .', . . .
~- . . . ~ . .......... - ~ . . .
1065274
selectively transport a sequence of chemical species for super-
imposed displays within a single EMP unit or cell.
The components of EMP media which are suitable for
use in an information storage and display system are generally -~
~ those with melting points in the neighborhood of room temperature.
- From any class compounds whose use in the media is indicated,
one or more media components may be chosen for their melting
point. For example, the class of phenols offers the following
choices: -
, lO Compound Melting Point
,.
~- 2,4-dichlorophenol 40-42
2,4-dimethylphenol 22-24
2,6-dimethylphenol 45-47
2,4-ditertiary-pentylphenol 24-26
2,6-ditertiary-butyl phenol 35-36 ;-
~ 2,6-ditertiary-butyl-p-cresol 62-68
- o-ethoxyphenol 25-27
p-methoxyphenol 54-56
l-phenyl-2-propanol 36
20 thiophenol 70-75
:
Lower melting compounds, such as 3-phenyl-1-propanol (MP=-18C)
,, .
and m-thiocresol (MP=-20C) may be useful in combination with
one or more of the compounds listed above.
, The use of EMP with melts is not restricted to room
; temperature melts. Additional media components which may be
employed include resins, glasses, glazes and chalcogenides.
Glycol-boric acid glasses are low-melting glasses
suitable for EMP media. Various mole ratios of boric acid or
. .~ .,
boric anhydride fused with most glycols yields a rigid trans-
parent glass at room temperature, suitable for modification
- 80 -
~r
~065274 ~
for EMP use. Starches, sugars, amines, borax and many other
compounds can also enter into the glass formation. Increasing
the ratio of glycol or amine to the boric acid adjustably lowers -~
the melting point. Similarly, agents such as metallic stearates
can act as crystallization retardants and can be used with, for
example, sugars to produce glassy EMP media. Rosin and
methacrylates are other organic glass forming media. Inorganic
glasses can be derived from phosphates, tellurium, selenium and
other materials. Iodine, as well as other compatible conducti-
vity agents may be used for adjusting the glass to EMP media
requirements.
EMP may be conducted in other solid media by applying
heat energy to liquify the media during EMP and allowing the
media subsequently to solidify. For example N-methylacetamide
was heated above its melting point and placed on a paper strip
("Whatman"* #1). The paper strip was suspended between electro-
des, rhodamine and ink dyes were then placed on the filter paper
and a potential applied across the paper. After the rhodamine
. .
dyes migrated, the molten n-methyl-acetamide was allowed to
cool and solidify.
Photoconductive materials, such as polyvinyl carbazole,
may be employed in conjunction with EMP effectuated information
storage, processing and display. For example, in an information
reproduction system, a conductive substrate may be coated with
polyvinyl carbazole. Where li~ht passing oVer or through the
document, film, object or other image to be reproduced strikes
:,
the polyvinyl carbazole, a short circuit will occur, and dye
molecules contained in a juxtaposed EMP media will not be caused
to move or will be under a reduced potential and therefore
subject to reduced movement. Where light does not strike the
:.
polyvinyl
* Trademark for a brand of filter paper made in England
- 81 -
. .
1065Z74
carbazole, dye molecules may be mobilized or deposited. Because
of the fast molecular migration achieved with EMP, such a repro-
duction process could be carried out a~ a much lawer voltage than
used in conventional electrostatic techniques. For example, a
.` 5 process of the type disclosed in U.S. Patent no. 3,384,566 to
Clark could be modified with use of EMP for opera~ion at lower
voltage and enhanced transport rates.
- EMP may be employed to obtain a number of electro-optic effect~. For instance, it may be used in a manner analogous
to electrophoresis in fluid glass-sandwich display techniques.
See Fluid Glass-Sandwich Display Technique Permits Large,
: Multicolored Characters, 22 Electronic Engineering Times (March
29, 1974). EMP would provide the-advantages of faster response,
wider selection of materials and less heat generation compared
to electrophoresis in such an application. EMP could also be used
in place of electrophoresi~ in applications such as that described
. .
in U.S. Pat. No. 3,511,651 to Rosenberg. EMP media may additionally
be used in electrochromic devices to form the junction material
between the electrochromic material of, e.g., molybdenum trioxide
on NESA glass and t~e second electrode. (Sulfuric acid has been
employed as the junction fluid in the past.) The technique
; of EMP media formulatlon may be used to modify or study
liquid crystals.
; The technlque of EMP media formulation may also be
use~ to modify the Kerr effect (alteration of a material's
influence on polarized light by imposition o~ a high voltage
electric field) in variouq 11quids.
Electromagnetic fields in addition to the driving
voltage may be employed in connection with EMP for various
purposes. A second electrode 4~tat angles to the set providing
82.
`
1065Z74
the driving voltage may be used to cause thechemicalspecies
being transported to swerve from a straight line path. Similarly,
one or more electrodes angulated to the set providing the
driving voltage may be used to compensate for any slight lateral
deviation or spreading of a species traveling on a substrate and
to counteract the effects of diffusion. In addition, a balanced
electrode pair may be placed perpendicular to the path of the
;-chemical species transported, and used to detect the passage of
various zone~ of chemical species based on the change in electrical
forces between the second set of electrodes.
; Pulsed DC fields may be used instead of a constant DC
driving force to reduce media heating. As an additional modifica-
tion, an AC field may be superimposed on the DC driving force
to mediate the dielectric and semiconductive properties of the
.
media, as well as to take advantage of the Debye-Falkenhagen
(solvent) effect.
Magnetic fields may also be employed to modify t~e
' EMP process. A magnetic field, preferably on the order of one
kilogauss or greater, applied at right angles to the EMP voltage
will, by virtue of the Faraday magneto-optic effect, cause the D
and L forms of stereoisomers transported under the influence of
EMP to separate into distinct paths. This procedure must be
carried out in an apparatus of special design. A suitable EMP
cell comprises two separable electrode compartments and sub-
strate (e.g., filter paper) clamping means. These compartmentsare mechanically fixed in position so as to allow the pole faces
of a puwerful electromagjnet to be brought within close proximity
to the ~op and underside of the substrate surface. An insulating
film such a~ ~Mylar~* can be used to retard arc-over to the pole
face. --
83. i-
* Trademark for a polyester (polyethylene terephthalate) film,
havinq very high tensile strength.
.'' ,~' . ' . .
.
- ~ \
:` 106SZ74
\
Magnetic fields may be used to stabilize the media so
as to reduce long-term diffusion of a molecular species during
a continuous EMP process in a manner analogous to that described
for electrophoresis in Kolin, Continuous Electrophoretic
Fractionation Stabilized by Electromagnetic Rotation, 46 Chemistry
509 (1960). Unlike the Kolin application, there is no significant
stabilization prob~em in EMP due to thermal factors. Further,
whereas it has been found that the magnetic response of the
migrating specieq in the aqueous electrophoretic media was nil,
the response of species in EMP media as well as the media
itself, will differ from electrophoretic aqueous media, and
can be further modified and controlled.
The invention herein includes the processes of impart-
ing mobility to or separating chemical species by providing a
semiconductive transport medium (which may be liquid, gaseous or
solid) and impressing a voltage of about 0.05 to 25,000 volts/cm
acroqs the medium sufficiently high to produce a current
denrity in the range of about 0.001 to 400 microamp/cm2 or
- .002 to 100 microamps/cm2 and equal to or exceeding the threshold
current value for the species in the medium, below which value
the species remains substantially stationary, to induce a high
'~ mobility rate for the species. In an aspect of this invention
the fluid semiconductive transport medium contains a component
selected from the group consisting of mobilizers and initiators
and comprises impressing a voltage within the range of about
0.05 to 50 volts/cm acros~ the medium sufficiently high to
produce a current density in the range of about .001 to 4 micro
amp/cm2, or from about .002 to 0.2 microamps/cm2 and equal to
or exceed the thre~hold current value for the species in the
medium, below which value the ~pecie3 remains substantially
.
84,
1()65279~
: stationary, to induce a high mobi~ity rate for the species.
Where the fluid semiconductive medium comprises water, a
conductivity suppressant, a high dielectric constant component,
and a component selected from the group consisting of mobilizers
S and initiators, the process for imparting mobility to a biochemical
species is carr~ied out by applying a voltage within the range
. of about 0.05 to 25,000 volts/cm across ~he medium sufficiently
high to produce a current density of at least 2 microamps/cm2
.
' or at least 20 microamps and equal to or exceeding the threshold
.j: O current value for the biochemucal species in the medium, below
which value the biochemical species remains substantially
stationary.
; Where EMP i~ carried out on a support member, an
: adsorbent may be used, such as cellulose, cellulose acetate,
S cellulose nitrate, alumina, silica, glass, asbestos, wood, flour
or resin as "Teflon", "Pevikon"*, or ion exchange resin as
"Amberliten** or modified cellulose, or molecular ~ieve resin
as "Sephadex"***, or mineral as diatomaceous earth or apatite.
* Trademark
** Trademark
*** Trademark
,'
:
. O
v -8s-
.- :
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