Note: Descriptions are shown in the official language in which they were submitted.
~ 1~L382;20
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This invention relates to apparatus for monitoring
repeatedly the absorption of electromagnetic radiation by a
plurality of specimens occurring during a period of time
More particularly, this invention concerns an apparatus by
which each of a plurality of samples provides a plurality of
aliquots which can be subjected to chemical reaction with
different reagents. The absorbance of each aliquot repeatedly
is measured during a predetermined reaction time. The
inputting of the samples, obtaining their aliquots, selecting
and adding of reagents, and the absorbance measuring all can be
efected in a continuous mode as well as a stat and a batch mode
of operation. The term "ali~uot" as employed herein is a noun
meaning a portion of a sample.
Apparatus de9cribed hereinafter would be well suited for
the measurement of kinetic reactions such ,as useful in enzyme
analysis as well as end point measurement. Many chemical
reactions reguire from a few seconds to many minutes to be
completed and, during such kinetic reaction time, it is often
important to observe the progress of the reaction by making
measurements several times One form of measurement is
ascertaining the absorbance of electromagnetic radiation of a
particular wavelength by the analyte. Typically, enzyme reaction
measurements have been accomplished by batch handling methods
~ and apparatuses re~uiring a considerable amount of preparation
t , 25 and manipulation by the laboratory technician. The nature of
the process cannot help but re5ult in relatively low throughput.
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~13~2ZO
Thc disadvantages of the previous proposals may be over-
come by progressively measuring absorbance changes in sample
alicluots in a plurality of cuvettes arranged in a circular ar-
ray which is rotatcd in a slow or step-by-step motion. As the
cuvcttes are advanced sample al:ic~uots are introduced int:o each
cuvette in a first position, cach aliqu~t is prepared for a
specific test by adding one or more reagents and the absorb-
ance changes are monitored by a plurality of photometers ro-
tating at a greater speed than the cuvettes and arranged to
direct radiant energy through each cuvette as each photometer
passes the cuvette and individually to gellerate an electri.cal
signal proportional to the instantaneous absorbance of the
particular aliquot at one of a plurality of wavelengths of
interest. Each aliquot is monitored numerous times by each
photometer before making a completc circuit and each ~ignal is
convert~d from an analog to a di~ital si~7nal before it is trans-
mitted from the rotating photometers to a stationary control
receiver or computer. Prior to arriving at the fi,rst position
after a complete circuit the tested ali.~uot .is removed rom
2C each cuvette which is then laundered so it is in conditi.on to
receive the next sample aliquot. In this manner there i.s al-
ways an endless array of cuvettes ready to receive the aliquots
to be tested.
The preferred embodiments of this invention will now be
described, by way of example, with reference to the drawings
accompanying this specification in which:
FIG. 1 is a perspective somewhat diagrammatic view of
one embodiment of the complete apparatus of the invention;
FIG. 2 is a fragmentary perspective view of the cuvettc
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turntable and the photometer rotor illustrating one embodiment
of the photometer means, portions being shown in section and
other portions being broken away;
Figure 3 is a median fragmentary sectional view through
the data generating components of the apparatus further detailing
the embodiment of Figure 2;
Figure 4 is a view similar to that of Figure 3, but
detailing a second embodiment of the photometer means and a
second embodiment of the data transmission arrangement;
~38;~0
Figure 4a is a fragmentary view of a portion of Figure 4
but illustrating a modified form of the invention utilizing a
split beam arranyernent; and
Figure 5 is an electrical block diagram primarily of the
portions of the apparatus concerned with the generation and
transmission of digitized absorbance data.
With reference to Figures 1 and 5 which are somewhat
diagrammatic, the subject apparatus can be composed of a control
console 10 and a chemistry processing portion 12. Input
information, concerning each sample and the different chemical
tests to be performed on aliquots of each specific sample, can
be supplied by way of a keyboard 14 and/or data cards fed into
a receiver 16 of suitable data input means 18. The input
information then is applied to a master control unit 20, which
has many functions, only some of which will be mentioned
hereina~ter, but those skilled in the art will appreciate the
more complete control ambit of this unit. A first function of
the master control unit 20 can be to feed the input inormation
to a readout unit 22, which can include a visual display 24 and
a printer of a tape 26, from which the operator can verify that
the input information has been entered accurately.
The master control unit 20 can store a list of commands
pertinent to each of the chemistry tests that the apparatus is
capable o~ performing. Thus, when the input :information
'5 associates a specific sample with a specific set of tests, and
assuming the apparatus has needed diluent and reagents, all that
remains to be accomplished by the human operator is to have
placed the sample into an appropriate one of the sample holders
3~3220
28 in a sample disc 30. Thereupon, the master control unit
20 can control the transferring of sample aliquots into cuvettes
32 mounted in an annular array in a turntable which is part of
the data generating portlon 34. An ali~uo-t and diluent transfer
mechanism 36, forms of which are known, can accomplish the
transferring, with each required chemistry test being associated
with an identified cuvette 32 for that specific sample. As
the several aliquots are being dispensed, the cuvette array
will be indexed forward one step for each cuvette and its
associated aliquot. As used herein, "step" and "indexed"
include but are not limited to discrete movements, since the
cuvette array could be continuously moving slowly.
A reagent supply area 38 has separate reagent containers
40 in a reagent disc 42, First and second reagent dispensers 44
and 46 will add appropriate reagents to specific cuvettes as
those cuvettes advance around the path of movement of the
annular array. The dispensing point of the first reagent
dispenser relative to the cuvette path is spaced several steps
prior to that of the second dispenser 46 so that in this space
interval, which corresponds to a known time interval, the first
reagent can have reacted with an aliquot prior to the introduction
of the second reagent. Some chemical tests may require the
addition of reagent from only one of the dispensers.
The aliquot and diluent transfer mechanism 36 as well as
the reagent dispensers 44 and 46 can be of the type which swing
arcuately between the source of fluid 28 or 40 and a cuvette 32.
Both when receiving and dispensing fluid the probe of the
dispensers can move down into the vessels 28, 32 and 40, but
would be elevated to be able to swing free thereo~ in an
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3~;ZZ~)
arcuate path.
Between the time and position that the aliquot is dis-
pensed and the first reagent is dispensed there i5 a distance
alony the path of the cllvettes duriny which measurement of the
transmittance of the aliquot with its diluent and the cuvette
walls can be accomplished. Just prior to the point that each
cuvette has made a complete circuit and is again being posi-
tioned beneath and aliquot dispenser mechanism 36 there is a
laundry stdtion 48 having probes and mechanisms for removing
the reactants, if any, from the cuvette, washing the cuvette
and making it usable for receipt of a new aliquot.
The data-generating means 34 are characterized by tl-e
presence of a plurality of photodete(tors radially arranged
around a rotor 56 and comprising a source of radiation such as
a lamp 50 and individual radiation detectors 52 which can be
photoelectric cells, photomultipliers or the like. Eacl- de-
tector 52 may have its own light source 50 as shown in the
embodiments of FIGS. 2 and 3 or there may be a single li.ght
source such as the lamp 50 in the embodiment of FIG. 4. (T}le
same reference numerals are applied to the same or equivalent
components in the two embodiments).
In the first embodiment the individual lamps 50 are lo~
cated outboard of the path followed by the circular array of
cuvettes, while in the second embodiment the single lamp S0
is located at the axis of the rotor 56.
In both embodiments the photodetector means are wholly
carried by the rotor 56 insofar as the source and detector 52
are concerned. The radiation paths 5~ in all events are at
most about the radius of the rotor 56 and usually, as for example
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in the embodiment of Figures 2 and 3, a fraction of the
rotor radius, Thus, the path is a few centimeters long and
has the barest minimum of optical elements in the train.
The advantages of the invention are principally derived
where there is a plurality of photometers mounted on the
rotor 56 but some of the advantages of the inv~ntion are
available if only one photometer is utilized; hence reference
to "photometer means" is intended to encompass both concepts,
It is clear that in a sin~le photometer as compared with a
rotor having eight photometers the rate at which data can be
gathered would be less for the single photometer than for the
multiple photometer device, assuming that the number of
cuvettes in the turntable and the speed o rotation of the
rotor are the same in both cases. A single photometer apparatus
can have its rate of data generation increased by increasing
its speed of rotation. The capacity of data handling, storage
and so on of the data processing means will be dependent upon
the amount of data being generated, Likewise the complexity
of the data processing means will be related to the variety of
data generated. All of these factors and more come into play
in the choice of the number of photometers, the speed o~ the
rotor, the wavelengths at which measurements are made, and
the chemical reactions which can be handled by the apparatus,
For comparison purposes it is pointed out that the
'5 scale of the drawings in Fi~ures 2 to ~ is such that the
diameter of the rotor 56 measured below the locàtion of the
lamps 50 in Figure 3 is approximately 30 centimeters so that the
total optical path from lamp 50 to the photoresponsive device is
1131~22~)
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less than about 2 centimeters in the embodiments of Figures 2
and 3 and less than about 8 centimeters in the embodiment of
Figure ~.
The circle of cuvettes 32 carried on the disc or turntable
74 rotates on the axis 58 which is also the axis of rotation
of the rotor 56. Thus, the cuvette array and the photometers
are concentric. The mounting and driving means for the rotor
56 and the turntable 74 will be detailed with reference to
Figures 2 to 4; however operational, timing and position
relationships can be considered with reference to Figure 1.
As mentioned above, the rotor 56 in Pi~ures 2 to 4 may be
considered to have a diameter of about 30 centimeters which
indicates a scale o roughly half-9ize in those Figures.
Figure 1 is illustrated at about one-fifth full size. In
neither case is this intended to be limiting since the invention
has broad application to many different forms and sizes of
apparatus.
It will be apparent from the foregoing that during its
complete circuit of movement for a single revolution of the
turntable 74 any given cuvette 32 will have had its aliquot
subjected to fluid processing, chemical reaction and measurement,
and as well will be prepared to receive a new aliquot for the
repetition of the cycle. The path of the cuvettes is a circle
in the apparatus which has been illustrated and will be described
as such, but modified forms of the invention may vary this.
The turntable 74 will be indexed at a relatively slow
rate, making a total of about five to t~7enty revolutions per
hour, with the periods of dwell somewhat longer than the perlods
--8 --
~138ZZ~)
of movement. This speed is said to be relatively slow in
contrast to the speed of the rotor 56 with i-ts photometers
which will be normally rotating at a speed of as much as several
hundred revolutions per minute. Thus, for each dwell period,
at which time the measurements are preferably programmed to be
taken, there can be many rotations oE the rotor taking place
with the corresponding number of measurements being made by all
- photometers of all cuvettes. Preferably there should be a
minimum of one revolution of rotor 56 per dwell period
In this way, many time spaced photometric measurements
of the reaction in any specific cuvette can be made, recorded
and/or stored for data processing in a single circuit of the
cuvette path, that i8~ during one revolution of the turntable 74.
The described mode of processing and endpoint aetermination can
lS readily be effected in this period of time, not only for the
aliquot in the single cuvette 32 but or a continuous number of
aliquots being added to and removed from the cuvettes 32 of the
turntable 74.
If there are 120 cuvettes 32 mounted on the turntable 74
and the turntable is indexed once every six seconds, one full
circult is achieved as a single revolution of the turntable 74
relative to the housing carrying the data generating components
34 every twelve minutes. If the rotor 56 and its eight photo-
meters rotate around the axis 58 at a speed of one revolution
`~5 every six seconds, this is a relatively slow speed of ten
revolutions per minute or 120 revolutions of the rotor 56 for
; each revolution of the turntable 74. If we assume that measure-
ments are being made at all times, each cuvette 32 of the array
_ 9 _
~3~ZZ{~
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on the turntable 74 will be scanned photometrically 960 times
in a complete circuit relative to the housing carrying the
data generating components, for example, relative to the point
where the aliquot has been inserted. If the speed o~ the rotor
56 is doubled the number of measurements will increase to 1920
times, but it should be appreciated that since this is ~or only
one cuvette and its aliquot, the total number of measurements
made in a single revolution of the turntable 74 is of the order
of 18,000 for the slower speed o the rotor 56 and 36,000 for
the double speed mentioned.
Since some of the positions whare cuvettes 32 will be
located will be employed for laundering the cuvettes, some will
be employed for injecting the aliquot and carrying the same to
the reagent insertion location and some may even be employed
for agitation, the total number of cuvette positions around
the circular path where the measurement or monitoring is taking
place may be less than the total number of cuvettes. Thus the
total number o measurements mentioned above may be less than
stated by an amount which takes into account the locations
needea for the above-mentioned functions. It might be mentioned
that monitoring may be continued at every position, if desired,
leaving the data processing control means to discard readings
which have no significance. Readings made during periods where
launderîng is taXing place could be equated to blank measurements
~5 and even some information can be acquired from the aliquot in
non-reactive condition beore the introduction o~ reagents For
the purposes o the discussion which follows, it will be assumed
that 800 separate photometric measurements can be made on each
aliquot where the rotor is rotating at ten revolutions per
_ 1~
~38;;~20
minute, there are 120 cuvettes, the indexing is taking place
at a rate of one revolution of the turntable 74 in twelve
minutes, each step o~ the indexiny occurs every 6 seconds and
there are several stations along the path of the cuvette array
which are occupied by functions that are not concerned with
photometric monitoring.
Since 800 measurement points of a reaction, each measurement
being three-fourths of a second apart during ten minutes, may
not be required and since certain chemical tests can be monitored
better at a specific wavelength, each of the photometers can be
provided with a specific filter 60 so that each photometer can
produce radiation and maXe measurements at its own wavelength.
~ssuming that each o~ the ~ilter5 60 is dif~erent and information
from a specific aliquot in a specific cuvette most valuably can
be obtained from only one of the eight photometers, then there
can be obtained ~rom such one photometer one hundred measure-
ments of the reaction of that one ali~uot during the ten minute
cycle because there is one measurement every six seconds.
Certainly, if it is desired that a reaction be monitored more
often than once every six seconds, more than one of the photo-
meters can be constructed to operate at the same wavelength.
It is pointed out that the photometers which are illustrated
in the drawings are equally spaced around the rotor 56, but
other arrangements where the photometers are grouped or spaced
~5 unequally are encompassed by the scope o~ the invention.
Bichromatic determinations may be desirable in pairs of photo-
meters very closely spaced.
As known, with the proper choice of reagents, several
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1138.'ZZ()
different reactions can be monitored at the same wavelength,
hence, with a capability of several different wavelengths and
suitable reayent selection, numerous different tests can be
processed by the apparatus. Since all of the cuvettes are
being scanned by each of the photometers, the availability of
different photometers monitoring at different wavelengths
permits aliquot alone as well as a reaction in a cuvette to
be monitored by more than one photometer and therefore at more
than one wavelength, with the separation of time between
monitoring at different wavelengths being three-fourths of a
second in the illustrated embodiment. It will of course vary
pursuant to construction and requirements. Each aliquot need
not be monitored at all wavelengths, nor does each sample have
to provide ali~uots for all tests capable of being achieved by
]5 use of the apparatus. The data into the input means 18 and the
master control unit 20 can be controlled and programmed in such
a manner as to command the execution of only those tests
requested for each sample and will employ cuvettes only as
needed, ther~by reducing the total amount required of sample
and reagent volumes and maximize the utilization of the cuvette
positions and the photometer means to maximize sample through-
put of the apparatus.
The apparatus does not require a fixed set of several tests
for each sample even if different ones of the set of tests would
not be requested for certain of the samples nor, as is also
well known in the prior art, does the apparatus cause empty
cuvettes representing "skipped" tests to occupy space in the
rotating array on the turntable 7~. The ~ust mentioned and other
~13Z~22~
sample processing control functions by the master control unit
are carried on a function control bus 62, shown in Figure 5~
It will be mentioned at this point by way of recapitulation
and emphasis that the apparatus of the invention has great
flexibility in being applicable to man~ choices of testing but
without sacrificing economy or throughput. As mentioned a~ove,
each aliquot need not be monitored on all wave lengths In
addition to this, each sample does not have to provide aliquots
for all tests capable of being accomplished by the apparatus
Test selection is here achieved without loss of analytical
capacity, without wasting any of the ali~uots or reagents,
without carrying out any unnecessary tests whose data are
u~eleqs and without skipping any cuvettes. On this account
it can be appreciated that the throughput of the apparatus is
also not af~ected by the great versatility of the device
It may be said of this apparatus that it has true test
selectivity without the equivocation of prior automatic
chemistry devices in that if a test is not performed in a given
cuvette that same cuvette is available for another test
~ext, with re~erence to Figures 2 and 3, the details o
one embodiment o~ the data generating component assembly 34 will
be discussed, with some reference also to Figure 4. As shown,
each radiation source 50 and its associated detector 52 are
relatively close together and on a line and securely mounted to
~5 the rotor 56 and thereby define therebetween the short radiation
path 54 of fixed length which lies on a radius from the axis 58.
The rotor 56 is arranged to rotate on the axis 58 and is provided
with a depending rotary sleeve 64 which is journaled on bearings
66 mounted to the housing base members 68 and 70. Suitable
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1~3822~
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drive means 72 can be coupled to the sleeve 64 to apply the
rotational movement to the rotor 56 and its photometers, two
of which are illustrated in Figure 3. The photometer components
ana the s'nort radiation paths 54 therebetween are thus held in
fixed orientation with respect to each other and their radial
orientation with respect to the axis 58. The journalled
mounting of the rotor 56 provides a precision orientation of
the radiation path 54 with respect to its distance from the
axis 58, such distance remaining substantially constant as the
rotor 56 is rotated.
The bearings 66 can be of any suitable conventional design
and construction. The criteria for such bearings are accuracy,
smoothness, reliability, in addition to providing the thrust
support needed in view of the weight of the rotor 56 and its
components. Radial support re~uirements in view of the weight
and ~orces generated during rotation of the rotor 56 must also
be taken into consideration in choosing the bearings 66.
The construction described together with a judicious choice
of high quality bearings 66 will result in accurate tracking of
the photometers during rotation of the rotor 56 thereby enabling
accurate and repetitively identical photometric measurements to
be taken during operation of the apparatus. Notwithstanding
precautions taken to assure accurate trac~ing and elimination of
any eccentricity during rotation, the nature of the invention is
such that some eccentricity during this rotation will not
adversely afect accuracy.
The annular array o cuvettes 32 is mounted on the turntable
74 as explained. These may be removable cuvettes or the turn-
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1~3E~'~20
q.~
table may be molded or otherwise formed with the cuvettes 32
permanently attached thereto. The turntable 74 is journalled
for rotation on the same axis 58 as that of the rotor 56 and
the disposition of the turntable is above the rotor 56 so that
access may be had to the entrances to the cuve-ttes 32 from above,
as will be explained. The array of cuvettes extend downwardly
~rom the body of the turntable 74 which is somewhat disc-like
or planar in character, defining an annular ring path through
which all of the cuvettes travel during rotation of the turntable
74. This ring intersects all of the radiation paths 54 of the
photometers mounted on the rotor 56. These paths 54 are radially
arranged about the rotor 56 and in the case of the very short
paths 54 of the embodiments of Figures 2 and 3 the spaces
between the filters 60 and the lamps 50 also define a slmilar
ring that coincides with tha~ formed by the path of cuvettes 32.
The photometers 50-52 can be mounted on the upper surface
of the rotor 56 in any suitable manner by clamps or bracXets
or the like or could be mounted on the interior of a thickened
disc forming the rotor which could be accurately molded to
~0~ receive the same. In such case, a groove or trough or annular
configuration could be formed in the upper surace of the rotor
56 in annular configuration to receive and clear the depending
array of cuvettes during their rotation. The radiation pa-ths
could then be arranged to pass through the groove in a radial
'5 direction which will enable them to pass unobstructed through
the walls of the cuvette where the aliquot being measured is
located. The cuvettes are obviously made out of some transparent
or translucent material and should have properly oriented ~alls
_15_
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113BZZ(~
that do not refract or scatter the beam o~ radiation passing
through the same.
The cuvette turntable 74 has a hub with depending collar
76, is centered on the axis 58 and is journalled for rotation
by means of bearings 78 that are mounted between the collar 76
and the sleeve 64, thus permitting the cuvette turntable to be
rotated independently of the rotation of the photometer rotor
56. Rotation of the turntable 74 in an indexing mode can be
effected by conventional means not shown in Figure 3, but
illustrated in Figure 4 and discussed with respect thereto,
Since the turntable 74 and the photometer rotor 56 are coaxial
on the same axis 58, and the collar 76 of the turntable 74
rotates within the sleeve 64 o the rotor 56, the path of the
cuvettes and the area sWept by the photometers are concentric
and the cuvettes are caused to intercep-t the short radiation
path 54 of each photometer with highly reproducible positional
accuracy thereby promoting accurate photometric measurements
without need for complex light guiding arrangements employed
in the prior art.
2C To enhance the continuously smooth rotary motion of the
photometer rotor 56 it can be designed with weighted circumfer-
ential volume to operate with a flywheel effect. In contrast
the cuvette turntable 74 should be relatively lightweight if the
indexing thereof is to be accomplished in steps with dwell
periods between steps.
Figure 4 illustrates primarily a slightly modified arrange-
ment of the photometer means 50-52. Such modification and other
differences between Figures 3 and 4 will be presented after the
discussion of Figure 5, which includes explanation of most of
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1138~20
the operation of the structure shown in both Figures 3 and ~.
As shown in Figures 3-5, the electrical output from the
radiation detectors 52 is coupled to electrical components for
analog to digital conversion and transmission from the data
generating component assembly 34 to the control console 10
(Figure 1). Preferably, the electrical components would be
secured to portions of the rotor 56 and its sleeve 64, by way
of circuit components, circuit boards and connectors such as
80 and 82, so that the electrical components can move along with
their associated photometers, during their rotation around the
axis 58, without the need for slip rings, commutators or the
like at the sensitive points of the circuit or more complex
wiring arrangements. The transmission of a l~rge quantity of
discrete electrical measurements in the form of analog values
from a plurality of radiation detectors 52 that is continuously
moving presents problems, both mechanical and electrical.
It is believed that the need for greater throughput of precise
data from many photometers, concerning numerous chemical tests
being carried out on a high number of aliquots, is not
~0 practically satisfied by the prior technology, The arrangement
in Figure 5 provides an efficient, flexible, yet simple and
precise mode of data transmission.
Commencing with the top left of Figure 5, there is shown
one of the assemblies mounted on the rotor 56 which will be
termed a photometer module 84 with its radiation source 50
directing its radiation to pass through the walls of one of the
cuvettes 32 and strike the sensitive surface of the detector 52,
after passing through the filter 60. The detector could be a
3%20
silicon diode, a photomultiplier, vacuum photodiode or other
photoresponsive device. A few milliseconds of scanning time
by one of the photometers moving past an effectively stationary
cuvette will be sufficient to obtain the required analog
measurement of the radiation incident on the detector 52 to
enable eventual calculation of absorption and absorbance. The
detector 52 responds to the amount of radiation transmitted
through the aliquot in the cuvette and the cuvette walls by
generating an electric signal proportional to such amount of
radiation. An integrator 86 is connected to the detector and
converts the generated signal to an output voltage signal which
is proportional to the transmittance of the ali~uot. A
logarithmic analog to digital converter 88 is coupled to the
output of the inteyrator and generates as its output on a line
90 a digital signal which is a function of the absorbance of
the aliquot. For ease of illustration, only one of the eight
photometer modules 84 is illustrated, but all eight of the
photometer output lines 90 are shown.
Since at one instantaneous position of the continuously
'O moving photometer rotor 56 all eight of the detectors 52 could
be respectively receiving radiation which has traversed the
samples in eight different cuvettes, a digital multiplexer 92
is connected to all of the photometer output lines 90. The
multiplexer operates in typical switching manner under the controlof
~5 a control unit 94, by way of a control line 96, discretely to
transfer the data from each o the log A/D converters 88 to the
data control unit on a data line 98. Such data can be handled
in the form of binary bits, with one binary word representing
_18_
~38;~ZO
the absorbance reading from one cuvette. The correlation of
each specific absorbance data word with its aliquot or cuvette
identification can be accomplished by the data control unit.
The means for such identification and coupling same to data
control unit are not illustrated. After the data word has
been transferred to the data control unit 94, that unit will
generate a reset command on a line lO0 to the appropriate log
A/D converter 88 to enable that converter to receive the next
analog signal derived from the next cuvette to be scanned by
that one photometer 84.
Each integrator 86 will be reset by its A/D converter
when its digital word is fed into the multiplexer. A reset
line 102 carries that command, usuall~ prior to the resetting
of the A/D converter by the data control unit 94. To ensure
that the radiation through one cuvette does not include
radiation from an adjacent cuvette as seen by its integrator 86
the integrator can be enabled by a start integrate command line
104 which can be triggered in response to one of various
conditions, such as: a timing relationship with the rotor
~o drive means 72, or a positioniny of the cuvette relative to the
radiation path 54, or the shape of the output signal waveform
from the detector 52.
Depending upon the sophistication of the data control unit
94 and the size of its memory, if any, the manner of data input-
'5 output handling can be variable. For example, by employing a
simple data control unit, each instance that a digital word is
~ed into the data control unit it can be transmitted to the
master control unit 20 and be processed therein for receipt by
the readout unit 22. The master control unit can have a data
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1138~2~
storage and correlation capacity as well as the earlier
mentioned function control, instruction and command information.
On the other hand, if the data control unit has sufficient
storaye capacity, at least all data words such as the 960
mentioned which are obtained during one or more rotations of
the rotor 56 can bé stored therein.
Assuming that each of the photometers 52 is operating at
a different wavelength and that a specific cuvette 32 is to be
monitored by only the one photometer 52 operating at that
wavelength which optimizes the measurement of the specific
reaction occurring in that cuvette, then of the 960 data words
received by the multiplexer 92 during one cycle or revolution
of the photometer rotor 56, only one hundred twenty oE tho~e
words (for the example described) normally would be needed by
the master control unit 20. The determination of which data
words are to be employed for data processing is developed from
the input information which associates specific samples with
specific tests. The master control unit 20 then assigns each
~ specific cuvette to a sample and a test and thereby a specific
photometer; whereupon, the data word require~ from that cuvette
for each revolution of the rotor 56 can be identified and
related to the data words from the same cuvette 32 obtained from
each of the next following rotor revolutions, which in the
preferred embodiment totals one hundred twenty revolutions of
'5 the photometer rotor 56.
Depending upon the desirable extent of communications
between the data control unit 94 and the master control unit 20,
the sizes of their memories, the speed of operation oE the
_20-
1~38~Z~)
apparatus, etc., all of which involve cost, throughput and
o~her factors which influence engineering design, the
erlgineering design can cause all ninety six thousand words to
~e transmitted to the master con~rol uni~ for its selection of
the needed twelve thousand data words; or, the two control
units 20 and 94 can communicate such that only the desired
twelve thousand words are transmitted from the data control
unit to the master control unit.
The engineering design is influenced by the timing of the
transmission of the data words from the data control unit to
the master control unit. There may be a finite amount of
unused time between the scanning of each cuvette, while the
rotor 56 is moving into alignment with the next set of eight
cuvettes, and also at the end of each revolution, when the
cuvette array is indexed one step. Since the apparatus can
operate in the continuous mode, as earlier described, one
revolution can be followed by the next without any significant
disruption, as contrasted to the batch mode of oparation.
Hence, data also can be transmitted in a continuous mode and
not stored until some later time and then dumped into a
processing unit. This continuous transmission of data from the
data generating component assembly 34 to the control console 10
may be with some control by the data control unit 9~, rather
than exclusively by the master control unit 20, as above-
'S mentioned.
In referring to unused time above, that is, time between
the scanning of cuvettes or at the end of a revolution, no
limitations on the invention are intended. Thus, it is feasible
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. . ,
1~.3fl~Z~:)
to measure dark current between cuvette scannings t~ set the
photome~er scales. The readings can readily be identified by
the conkrol unit and processed as desired and programmed.
Although a continuous operation mode has well known
advantages over batch operation, there can be conditions
which warrant batch handling. The appara-tus of this invention
can be used in batch processing. For example, the entire
cuvette turntable 74 could be in the form of a removable disc
to be replaced by one or more similar discs having the cuvettes
already filled with aliquots and possibly even reagents, each
replacement disc being a batch. If the batch would consist
of only a few aliquots, the cuvette disc could be constructed
in segments and then only a segment or portion of the disc be
replaced with a prepared segment of cuvettes. Likewise, a
stat or urgently needed test could be "inserted" into the
apparatus.
Such a structure would have a turntable like that shown
at 74 with a thin plastic disc, perhaps formed by vacuum molding
a synthetic resin sheet with the depressions ~orming the
cuvett-s, capable of being clamped or snapped onto the upper
sur~ace of the turntable. The operation of the apparatus would
not be too much different, being re~uired only to enable proper
orientation of the replaceable disc to provide sample
identi~icatiOn and with some modification which starts and stops
the apparatus so that the attendant may remove the used disc
and replace it with a new one.
In normal operation $UCh a disc or -turntable would not be
required to rotate and its cuvettes would be scanned by the
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1~38;~Z~
plurality of photometers during rotation of the rotor 56.
Stepping of the disc or turntable 7~ would be useful where the
apE~aratus could be alternated between continuous and batch
mocles. The removability of the disc on tlle turntable 7~ could
S be of advantage where stat testing is -to be done and it is not
desired to integrate such tests in with the routine ones being
processed. Stepping could also be of advantage along with
removability in a batch mode where the steps carry different
sets of filters into the radiation paths.
In a batch method device where the rotor carries a plurality
of photom~ters, such photometers could employ individual lamps
50 for each photodetector 62 or a single central source of
radiation serving all photometers
One variation of the invention could comprise a fixed or
~ndexing turntable with cuvettes and a rotor having a single
photometer, the rotor also carries a filter wheel arranged
vertically and intercepting the beam of radiation from the
photometer before it passes through the cuvettes. The rotor
in such case is arranged to stop momentarily at each cuvette
an:d automatically rotate the filter wheel to provide several
measurements at different wavelengthsthat are identified by
suitable synchronizing means to be sent to the proper address
of the storage or recording device through data control means.
In this way, the effect of plural photometers is achieved
S without the need for any duplication of photometers.
It is pointed out that the reference to the rotation or
; revolutions of the rotor 56 is not to be considered limited
to movement in one direction since it is feasible for the rotor
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1~38Z20
56 to oscillate by rotating substantially one revolution and
then reversing itself to rotate a revolution in the Opposite
direction, etc.
Next, with xeference to Figure 5, there will be disclosed
both types of data flow and control; first, that which requires
two-way cornmunications between the control units 20 and 94;
and second, one-way communications. The latter, although
simpler than the former, would require more sophistication
and also more storage capacity by the master control unit.
Two-way communications between the master control unit
and the data control unit can be accomplished with the aid of
a pair of communications logic units 106 and 108, a pair of
transmitters 110 and 112, and a pair of receivers 11~ and 116.
The elements 106, 110 and 114 would be housed in the rotating
portion of the data generating component assembly 34. The
corresponding elements 108, 112 and 116 would be located in
the control console 10 and/or a stationary portion of the
assembly 34. A control bus 118 and a data bus 120 link the
data control unit 94 with its communications logic unit 106.
In like manner, control and data buses 122 and 124
link the master control unit 20 with the communications logic
unit 108. Typical of the bidirectional control information
on the buses 118 and 122 would be the availability of one or
; more data words to be written into or read from one or the
other or both of the memories in the units 20 and 94 and the
availability of the associated logic unit 106 and 108 to receive
or transmit such data.
Since in the now being described embodiment of the
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;
1138ZZO
electronics there is to be two-way communications between
the data control unit in the reaction table and the master
control unit in the control console, the control and data
buses 118-12~ will be bidirectional as indicated by the
arrowheads in Figure 5. Also, the communications logic
units 106 and 108 will possess two-way capabilities.
The bidirectional data buses 120 and 124 will carry each
data word serially in parallel bit order, but the inputs from
the receivers 114 and 116 and the outputs to the transmitters
110 and 112 will be serially by bit. The preferred embodiments
of the transmitters and receivers, as illustrated in Figures 3
and 5, respectively are photoemissive and photosensitive,
Figure 4 employs a slip ring assembly 110-116~ however, other
forms of transmission and reception are possible, such as of
the radio frequency type, and are encompassed within the general
terms and are not to be considered limited by the illustration
of the preferred embodiments.
Phototransmission, as by a photodiode~ is both simple
and well suited to the handling of binary serial bit data and
is well known to those skilled in the art. Moreover, photo-
emission and reception are less subject to interference than
radio transmission, especially when the elements 110~116 can be
closel~ spaced.
As shown in Figure 3, the transmitter 110 and receiver 114
can be housed within the sleeve 64 and rotate therewith close
to the axis 58. The associated elements 116 and 112 could be
stationary and lie close to the projection of the axis 58 and be
wired into the logic unit 108 in the control console 10.
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1~.3R~
Mounted in such a manner close to axis 58, the fact that the
transmitter 110 and receiver 11~ are rotating will not cause
errors in the binary bit data transmission. On the other hand,
i~ the magnitude of a signal, rather than presence or absence
thereof, were the measure of the test data and the control
commands, then relative movement of the transmitters and
receivers could produce transmission errors~
From the foregoing it will be appreciated that for
economical use of storage capacity in the master control unit
20 only the desired data words should be transmitted from the
data control unit 94. To effect such economy the input
information from the data input means 18 will enable the master
control unit to establish a listing of the aliquots or their
cuvettes from which data i~ desired. As new samples are
added to the sample disc 30, associated input information fed
into the master control unit and old samples complete their
testing the "desired" listing will be updated continuously.
As each data word is received by the data control unit 94 from
the multiplexer 92 it will, by two-way communications, be
checked with the desired data list and only be transmitted to
the master control unit after an affirmative comparison. This
communication ~ill require the data control unit and its logic
unit to have interchanges on the buses 118 and 120 regarding:
the fact that a data word has been received from the multiplexer,
identification of that word and that the logic units 106 and
108 are ready to communicate that identification information
to the master control unit.
In like manner, the master control unit and its buses
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~13~ZZ(~
122 and 124 with its logic unit 108 will: acknowledge
availability to communicate, receive the identification data,
provide a comparison reply and then either cause the data word
to be discarded by the data control unit or cause it to be
transmitted for storage by the master control unit.
Each communication will require transmission and receipt by
one or the other pair of components 110 and 116, or 112 and
114.
In the other embodied form of data communications, all
data words are transmitted from the data control unit 94 to
the master control unit 20 and the latter then itself will
decide which data words to continue to store for ultimate
readout purposes. Becau~e of thi9 9impler form of con~unications
the data buses 120 and 124 need only feed in the direction
toward the master control unit, the communications logic unit
106 will operate onl~ as a sending unit, the communications
logic unit 108 will operate only as a receiving unit and the
transmitter-receiver pair of elements 112 and 114 will not be
required. The bidirectional control buses 118 and 122 between
the control units and their respective communications logic
units are required for the purposes above-mentioned
The differences between the embodiments of Figures 3 and 4
will now be described. First, concerning the photometer means,
the radiation source 50 of Figure 4 is located at the axis 58
and comprises a single element tungsten lamp rather than a
plurality of lamps positioned around the periphery of the
photometer rotor 56 as in Figure 3. The source 50 in Figure 4
is connected to the rotor 56 for rotation therewith.
_27_
~.3~ 0
A plurality of lens-containing optical tubes 126 are
mounted to the photometer rotor 56 o~ Figure 4 such that one
end oE each tube is proximate to the radiation source 50 and
the other end of each tube is close to the annular path or
pattern traversed by the cuvettes and is aligned with a specific
one of the radiation or photometric detectors 52~ The photo-
metric detectors 52 are also mounted on the rotor 56 substantially
as in the Figure 3 embodiment. The paths or patterns swept by
the beams of radiati~n reaching each detector is in effect the
same as in Figure 3.
One advantage of employing a single source 50 is that it
is easier to dissipate the heat generated thereby and thus
easier to regulate the temperature of the cuv~ttes 32. Note
that in the embodiment shown in Figure 3 the individual lamps
are located quite close to the annular ring defined by the
cu~ette path so that the heat of these lamps could be radiated
or transmitted to the materials carried by the cuvettes
The nature of many of the reactions whose characteristics are
being measured is such that temperature changes are critical.
As a matter of fact, means will often be provided for incubation
of the cuvettes during their scanning and the arrangement of
Figure 4 enables such structure to be easier achieved and more
effective in operation because of the absence of heat sources.
Another advantage of a single source such as in Figure 4
is that there is no problem with different intensities, colors
or wavelengths which can be expected in a plurality of different
lamps, even where matched. Whatever happens to the single source
lamp 50 happens to all readings made so that the effect is not
felt where relative measurements are made. The lamp 50 can be
1~.3~2ZO
cooled very easily by air circulated in its vicinity in a
manner which will not cool, for example, the cuvettes, The
power supply for a single source 50 is simpler and more
economical,
In the views described thus far shown there is a single
beam 54 which passes through the cuvette 32 and thence impinges
upon the photodetector 52 after passing through a filter 60 which
is usually in close proximity if not incorporated into the
photodetector. In the structure of Figure 4 it is feasible to
focus the light beam into a very fine pencil for passage
through the lower portion of the cuvettes 32 but in addition it
is feasible to incorporate beam splitting means into the
focussing tube or outside thereof to provide two beams which
may be directed in parallel paths through different levels of
the cuvettes for investigating different strata of the analyte,
Such a structure is shown in Figure 4a to be described in
detail below.
In Figure 4a components equivalent to those of Figure 4
carry the same reference numerals primed. The rotor 56' has a
focussing tube 126' which directs a beam 54' derived from a
source such as 50 (not shown in Figure 4a) to a semisilvered
or dichroic mirror 150 arranged at 45 in front of the tube
126'. A part of the beam passes through the mirror 150 and
becomes a bottom beam 54'b and another is reflected at 90
upward and thence reflected from the 45 angled mirror 152 to
become the upper beam 54'u. These beams pass through dif~erent
levels of the liquid 154 carried in the cuvette 32' mounted in
thè turntab'e 74' which is disposed to move in a path which
_29_
~ ~lA 38 ;~ Z~)
carries it and its companion cuvettes through the groove 156
provided in the rotor 56.
There are two photodetectors at 52' and 52" mounted on
the rotor 56 in suitable cavities aligned with the mirrors
150 and 152, respectively, and thus aligned to receive the
beams 54'b and 54'u against their sensitive surfaces. ~ach is
provided with a filter 60' and 60", respectively. Openings
158 and 160 respectively enable the beams to pass.
It will be obvious that the beam 54' emerging from the
10 focussing tube 126' splits, part going through a lower stratum
of the liquid 154 and part going through an upper stratum of
the same li~uid. The photodetectors 52' and 52" are
independent, each providing a different siynal which can be
transmitted through suitable connections to data processing
15 equipment to provide additional information concerning the
reaction which may be going on in the cuvette 32'.
Figure 4 shows the drive means for the cuvette turntable
74, which was not illustrated in Figure 3, because of drawing
space limitations. ~ motor 128 has its drive sha~t 130
20 coupled by a pinion gear 132 to a suitably mating configuration
134 on the periphery of the turntable 74. If the indexing of
the cuvettes is to be in steps, the motor 128 could be a
stepping motor, or there could be provided linkage, clutch
means, etc., for providing appropriately timed stepping from a
; 25 continuously driven motor.
As earlier mentioned briefly, a slip ring assembly 110-116
can provide the receiver and transmitter needs of the apparatus
and couple data and other communications from and to the
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1~1.3~;~20
reaction table 34 and the master control unit 20.
From the above, it now should be understood how the
e~ltire apparatus operates with its moving photometer means
and preferably in a continuous mode to place into the master
control unit 20 the digitized values of the readings related
to absorbance from the data generating components assembly 34.
Since reaction can be monitored at frequent intervals during
a prolonged period of time rather than a small portion thereof,
both rate and end point data are obtainable. Once into the
master control unit, the raw data can be associated with each
test and supplied to the readout unit 22 without any data
reduction, conversion or analysis, such being left to the skill
of a technician in interpreting the same~ In a pre~erred mode
of operation the master control unit would have the capability
of associating the data for each test, obtaining mathematic
rate and/or end point determination, then converting that
information into a reading of the chemistry value in the
desired concentration units for the test, thereafter feeding
the results into the readout unit.
Although some variations in structure and operation of
this chemical reaction monitoring apparatus have been disclosed
hereinabove, other variations are capable of being made. For
example, the preferred embodiments teach continuous movement
of the photometer rotor; however, a stepping device movement can
; 25 be employed. Also, the photometer means are spaced around the
circumference of their support, since such positioniny enables
a uni~orm weight diskribution around th~ support; however, the
photometer means could be mounted with variable spacing especially
1~ 38;~20
-
if the path of motion i5 other than circular. It may be
desired to employ disposable cuvettes. If so, the laundry
station 48 would be replaced by means for removing used
cuvettes and for insertiny clean cuvettes into the cuvette
turntable 74. At least in such situation, the cuvettes need
not move around a closed path. Reagents need not be liquid
but may dispensed dry. Cuvettes may be used in a disposable
mode with the reagent already in place, requiring only the
addition of the aliquot and a diluent.
,~
:::
.
_32-
