Note: Descriptions are shown in the official language in which they were submitted.
'73~ `
:
BACXGROUND OF THE INVENTION
Classical instrumental analytical chemistry has
always required that a test reagen~ which usually com-
; prises several separate components, be physically manipu-
lated and manually contacted with the fluid being tested.
This is usually followed by manually presenting the chemi-
cal reactants to an instrument for a quantitative readout
or estimation of the reaction products. Recently, however,
completely automatic instruments have been developed to
eIiminate the need for manual manipulation of the chemical
: ::
. ~ 1 - .
~9
,,
~ 7 ~ ~ ~
1 reactants and which give programmed readouts. Such instru-
ments are almost always extremely expensive and complicated
and the servicing of such instruments requires highly
skilled technicians.
On the other hand, when attempts are made to simplify
automatic systems, one usually encounters the problem
that semi-automatic instrument parameters must be set manu-
ally. In such instruments there is always the danger that
the instrument will be incorrectly programmed by the
technician. Thus, a proper balance must be made between
complex automatic instruments which require highly skilled
service personnel and semi-automatic or manual instruments
which require the programming and/os manipulation thereof
by relatiYely unskilled technical operatoTs.
12 Another disad~antage associated with awtomatic and
semi-automatic instrumental analysis systems is that when
a malfunction occurs in the instrument, all analytical
activity is suspended and recourse must be had to alter-
native procedures which are not familiar to the technician.
DESCRIPTION OF THF PRIOR ART
The prior art relatting to automatic and semi-automatic
analytical chemistry instruments is so extensi~e as ~o be
beyond the scope of this specification. As for the pre-
ferred and specifio embodiments of this in~ention, there
~` 25 is no known direct prior art.
, .
', '`
.'~ `
; ,''
,' ..
~3~3~
SUM~ARY OF TH~ INVI~NTION
The present invention relates to a simplified ~wo
component test system ~or ~emi-automatically determining
any selected ones of a plurality of constituents in a test
fluid. One component consists of a plurality of diffeTent
coded test de~ices each con~aining one or more immobilized
test reagents which give detectable chemical responses or
reactions to the particular constituents in the ~est fluid
being assayed. The second component comprises a test
instrument adapted to receiYe any selected one of the
coded test devices~ This instrument contains a code sens-
ing means and a reaction sensing means which is automati-
cally activated by the code sensing means to read ~hose
test reagents associated with the test device presented to
the înstrument. A readout means is included which is
coupled to the code sensin~ means and the reaction sensing
;I means to correlate the response of the instrument to the
particular device presented to the instrument and to report
the resul~s thereof. Preferred embodiments comprise the use
1 20 of dry or immobilized test reagents incorporated with
~I carrier mem~ers, such as strips of transparent plastic oil,
I to form the test devices,of the present invention. These
,I test devices can be used independently of the instrument if
, the ~esponse thereof is chromo~enic Another preferred em-
bodiment is ~he use of a code means associated with the test
`, device which not only provides for the programming of the
instrument according to the test device presented but also
automatically calibrates the instrument each time ~ test is
~`` conducted.
37~3
RIEF DESCRIP~ION OF THE DRAWINGS
Figure 1 is a plan view showing fifteen diffeTent test
devices o the type which is useful in the test system of
the present invention.
Figure 2 is a block diagram showing one form of an
instrument which is used to read the response of ~he ~est
devices shown in Figure 1.
Figure 3a to 3f are diagrammatic side-elevational
views of a part of the instrument shown in Figures 2 and 4.
~igure 4 is a block diagram similar to Figure 2 show-
ing in mo~e detail the circuitry of an exemplary embodiment
of the instrument shown in Figure 1.
D~SC~IPTION OF THE PRE~ERRED EMB~DIMENTS
The test devices of the present invention each com-
prise three components: ~1) one or more test reagents
which are specifically reactable with the particular sub-
stance or substances to be detected în the test fluid;
(2) a carrier member for the test reagent OT reagents, and
(3) a code means associated with the test device which
identifies the particular test device presented to the
test instrument, which instrument will be described herein-
ater.
Each of the test reagents associated with the test
devices of the present invention usually comprises one
or more chemical constituents which specifically react with
the substance in the test fluid to give a detectable
chemical response which relates to the amount of the con-
stituent in the test fluid, which response may be measured
instr~llentally. This response may be spectral, such as by
the selective reflectance of visual, ultraviolet or infrared
- 4 -
~737~
1 radiant energy or it may be any other physical or chemical
effect of any specific reactlon between the test reagent
and the constituent being detected, which effect is measur-
able using instTumental reaction sensing means. The test
eagent is preferably in a dry or substantially dry form
and is incorporated with a carrier member as will be
described hereinafter.
Specific test reagents will be described in detail
in the Examples; however, it should be noted here that
preferable test reagent systems comprise one o~ more
chemicals which can be combined prior to use and ~etain
their react;~ity for extended periods of time. Anothe~
preferable feature of such test reagents is the ability
thereo to detect the level of the par~icular constituent
1~ being assayed in the concentration range usually encoun-
tered in the test fluid
The second essential component of ~he test device is
the carrier member. This component comprises a means for
retaining or holding the test reagent and preferably for
allowing facile contact between the test reagent and test
fluid. Although a simple containeT may suffice or such
a carrier member, it has been found that a bibulous matrix
such as paper is ideally suited for incorporating the test
reagent in a dry or substantially dTy format. As will be
explained more fully in the descTiption of Figure 1 and
later in the operation of the present test system, it is
preferable to utilize ~ strip of transparent plastic film
to hold individual paper matrices into or onto which the
test reagents are impregnated. In such an embodiment the
- 5 -
:
.
~l~BL~3~
papar matrix and the trans~arent plastic film together
form khe carrier member and the part of the test device
comprisin~ the test reagent incorporated in~o the matrix
is called th~ reagen~ blo~k.
Alternatively, the carrier member may compxise simply
a strip of transparent plastic film on which the test re-
agents are affixed by any sui~able means such as, for
example, by a polymeric material. In such an exemplary
embodiment the test reagent is dissolved or dispersed in
an organic solvent solution of a polymer, such as cellulose
acetate, and th~ solution or dispersion is cast or other-
wise applied onto the transparent film and dried.
The carrier members ~described hereinabova may be
in the form of individual strips to which one or several
paper matrices are at~ached, or they may ~e in ~he form of
continuous rolls of plastic ~ilm comprising units of ~`
individual test devices which may be torn o~f, contacted
with the test solution and presented ~o the ins~rument.
The third component of the test devica is the code
means. This enables the instrument to determine which of
several test devices, having one or more different test
reagents associated therewith, is presented so that the
instrument ls programmed to read that particular test de-
vice. The code means is preferably a distinctive indicia or
placement thereof associated with the carrier member~ said
code means being specific or a particular test device and
recognizable by the instrumen The code means may be a
series of characters or ma~ks, each peculiar to a particular
test de~ice in a series of device~. ~he code means may also
~e a particular color which the code sensing means of the
instrument can recognize, as will be explained more fully
-6-
:~
: , ~ ~, . .; .
~ 3 ~ ~
hereinafter, The code means may also simply consist of an
opaque area, the placement of which is distinctive for each
test device. Other code means and formats will be apparent
from the above and the ensuing di~closure.
Exemplary of the various types of indicia which may
serve as code means for the ~est devices o the present
invention are: s~mbols such as diamonds, squares, circles,
and so ~orth; several marks of the same ~ype such as a
series of parallel bars; names, such as ~he name of the
particular test, iOeO glucose, protein, and so forth;
colors; numbers; slots; holes, and so forth. The only
limiting factor in selec~ing the indicia for the code m~ans
is that the instrument code sensing means mus~ be capable
of recognizing the indicia and dis~inguishing one from
another as well as coxrela~ing the particular indicia to
the test device.
-! A preferable code means is shown in Figure 1 and will
be described more fully later; however, basically this
preferable means comprises an opaque area or code blGck
placed on a transparent strip or carrier in predetermined
spacial relationship with one or more reagent areas ~r
blocks on the same strip, the location of the reagent
block or blocks with respect to the code block being dif-
~erent for each of the test devices used with the test
instrument. In use, a test device pre~ented to the in~tru-
ment is advanced to a position which interrupts a light path
between a light source and light sensing means, such as
a photosensitive element, the relative positions oE the
code block and the reagent block being indicative o~ a
30 specific test device,
`
..
--7
~737~
l Referring now to the test instrument, there are four
facets of this instrument which will be-described. The
first is that the instrument must be capable of receiving
or is adapted to receive the test devices of the present
invention, Secondly, the instrument must have a code sens-
ing means associated therewith in order to read the code
means of the test device and translate this signal into
a calibration reference signal and a command for the in-
strument to read the particular test reagent or reagents of
the test device. Third, the instrument must have a reaction
sensing means or receptor to detect ~nd accumulate the
response from the reaction of the test reagent and the
constituent in the test fluid being detected. The fourth
component or facet of the instrument is the readout means
which translates the response of ~he code sensing means and -
the reaction sensing means into a value which is indicative
of the quantity of the constituent being assayed in the test
fluid.
These facets or components will now be individually
discussed.
The irst facet or aspect of the test instrument is
that it must be able to receive ~he test de~ice relating
thereto. In other words, if the test de~ice response is
a color change on a paper matrix, the test instrument must
be capable of receiving the paper mat~ix, and the reaction
sensing means of the instrument must be capable of reading
the response, for example, by reflectance spectrophotometry.
The code sensing means may be any electronic device,
. .
component or circuit which can readJ identify and elec-
tronically process the indicia of the code means of the
test device to enable the instrument to identify the
. . . . . .
.
~ 7 ~
1 particular test being presented. The code sensing means
may also perform other functions such as that of a light
sensitive detector which can be used to command the instru-
ment to read a response at a particular time. This will
be explained more fully hereinafter.
More specifically, the code sensing means may be a
light sensitive detector comprising a light source direct-
ing a light beam at a photosensitive element or pho~osensor
or it may be a complex word or symbol reader such as those
used to read numbers on commercial o~ financial instruments
or notes. Additionally, the code sensing means may be a
color sensing device which identifies a pa~ticular color
or shade of color and correlates the color or shade with a
particular test device, Shades of gray may also be used
to ide,ntify the device. The code sensing means may also
be one which identifies a particular number of parallel bars
or opaque marks on the test device and accordingly identi-
fies a specific device. It will be appreciated from the
above, that numerous code means and code sensing means may
, 20 be used in conjunction with the present invention,
The third part of the test instrument is the reaction
sensing means. This component or means basically comprises
the part of the test ins,trument which recognizes and quan-
titatively measures the extent of the chemical reaction
2S be~ween ~he test reagents associated with the test device
and the particular constituents or chemicals being tested
for in the test fluid. The reaction sensing means may
simply be a photosensitive element or photosensor such as
a photoelectric cell which measures the light reflected from
a reagent block after a chromogenic reaction between the
constituent and the test reagent, or it may comprise more
complex analytical instrumentationO The controlling con-
_ g
737~
1 sideration is that the reaction sensing means must be cap-
able of detecting and quantitatively measuring the above
-noted chemical reaction, and of generating a signal which
is supplied to the input of the readout means which will
now be described.
The readout means correlates the output from the code
sensing means and the reaction s~nsing m~ans such that
(1) the instrument recognizes the particular tes~ device
being presented and (2) the signal or signals generated
from the reaction sensing means are processed to give an
indication of the amount of a particular constituent in the
fluid being tested.
A particularly advantageous and preferable readout
means of the test instrument of the present invention
comprises the use of an apparatus or electronic circuit
comprising an input scaler, an access scaler and a read
-only me~ory connected in such a fashion that the signal
or output from the reaction sensing means is decoded to
provide an indication of a characteris~ic or significant
quantitative value or range of values for the test fluid,
such as p~, clinical levels of glucose, protein, and so
- forth. Such circuitry is further described in the specific
embodiments which follow'
Referring now to Figure 1 of the dTawing, each of the
test devices numbered 1 to 15 illustrated therein comprises
a strip of transparent plastic film which forms a base
member 16 to one end portion o which one or more square
paper matrices 18 is affixed. The other end portion of mem-
ber 16 provides a handle for the test device- The matrices
18 are incorporated with test rea~ents which ~r~ ~n~cifi-
cally reactable with various characteristiCS or constituents
- 10 -
. ., , ~-
,- ~; - . - ,
:.
.~ .
~;~3~ ~7 ~
1 in test fluids such ~s urine. In the drawing, pH repTesents
a matrix incorporated with reagent to form a reagent bl~ck
for determination of the pH, while P, G, K, BI, BL and U
respectively r~present reagent blocks which are specifically
reactable with protein, glucose, ketones, bilirubin, occult
blood and urobilinogen. In the test devices shown, the code
means is an opaque area or printed area 17 which is identi-
fied in the drawing by the word "code".
In Figu~e 1 $he test device 1 is shown as having seven
test blocks 18 and a code block 17 disposed in spaced Tela-
tion on strip 16 beginning at the ri~ht hand end thereof.
The positions of the code block and reagent blocks of
device 1 are indicated by the letters P-l to P-8 shown
thereabove. It will be observed that with the devices 1
to 15 disposed in the vertical alignment shown, each of the
devices 2 to 15 has one or more spaced reagent blocks there-
; on, beginning at the right hand end thereof, and one code
; block. Each of th~ reagent blocks and code blocks is in
vertical alignment with one of the positions P-l to P-8.
For example, on test device 7, the code block is in position
P-3 and the pH, glucose and protein reagent bloc~s are in
positions P-6, P-7 and P-8 respectively. P-O represents a
start position on the handle portion of the strip 16 and P-9
I represe~ts a stop position beyond the right hand end of
strip 16, the significance of which will appear hereinafter.
The utilization of the test devices shown in Figure 1 with-
in the framework of the present invention will be more fully
described hereinafter as will the preparation of a test de-
vice.
3~ Figure 2 is partially a block diagram showing $he
various components of a test instrument as well as a
perspective view of a test device as shown in Figure 1 and
ce~tain xela~ed instrument c~mponents. This figure also
~hows the relationship of the test device to the test
instrumentO In this fi~ure; the test device shown is the
test device 10 of Figure 1 which comprises a code means 17
consisting of an opaque white block and reagent blocks 18a,
18b and 18c affixed to a strip of transparent film 16. The
reagent blocks 18a, 18b, and 18c are paper matrices impreg-
nated respec~ively with pH, pro~ein and occult blood speci-
fic test reagents.
The instrument diagrammed in Figure 2 comprises a trans-
parent glass or plastic table 43 sui~ab~ ~mounted for
reciprocating movement and connected to a suita~le recipro-
ca~ing actuator mechanism ~5, The actuator 45 is operable
to move the ~able 43 across a light beam from a source 37
conveyed via fibre op~ics 40, as will be more fully des-
cribed in Figures 3a to 3f. The ~able 43 may be provided
with positioning means, such as guide lines 43a and 43b or
suitable shoulder means ~not shown) to aid in proper place-
ment of a test device 10 thereon.
Actuator 45 is controlled by a timer 21 via path 39
which is in turn controlled ~y a start switch 44 via path
46. ~ delay circuit, not shown, may be associated with
timer 21 to provide a time lag between actuation of start
switch 44 and initial movement of the table 43, during which
;~ time lag a test device 10 can be placed on table 43. The
light emitted from fibre optics 40 is directed toward a
photosensitive element 41 suitably mounted below table 43~
: Upon a~tuation of start switch 44, the table 43 is
moved from its start position in the direction indicated in
Figure 2 to cau~e the code block 17 of device 10 to move
: into and interrupt the beam from light source 37, the light
-12-
.. . . . . .
.
~ 37 ~
1 thereupon being reflected back through fibre optics 40a to
a photosensitive element 38 which is suitably mounted in a
position above ~he level of table 43. As the code block 17
passes b~yond the light beam, said beam passes through the
transparent film 16 in the space between code block 17 and
the next adjacent reagent block 18a and through table 43,
striking the photosensitive element 41. Reagent block 18a
which for purposes o~ description will be assumed to have
reacted specifically to the pH of ~he ~est fluid to produce
a response, then moves into the light beam, again inter-
rupting the light striking photosensitive element 41, Ligh~
is then reflected to photosensitive element 38 in an amount
dependent upon the pH of the test fluid and the response of
reagent block 18a. The reagent blocks 18b and 18c are then
successively moved into readout position with movement o
the table 43 in the direction indicated in Figure 2j and the
response of the reagent in each block is sensed by the
. photosensitive element 38. Figures 3a ~o 3f give a more
detailed description of the movement of table 43 and the
functioning of code blork 17 as a code means.
The response of photosensiti~e element 38 is an
; electrical signal which ,is conducted over path 22 to the
. calibrate and amplify module 2~. The module 23 processes
the initial calibrate signal from code block 17 as well as
. 25 the subsequent signals generated from the reagent blocXs
l 18a, 18b and 18c. The signal from photosensitive elemen~
41, which is interrupted when the light beam 1S interrupted
by any of the blocXs 17, 18a, 18b and 18c, is conducted over
path 42 to the code sensor and read signal module 19
.
- 13 -
,'''
. ... . ., ~ . :. - :
'f~ ib~t7~
The logic by which the code sensor interprets the
interrupted signal will be explained hereinafter; however,
the photosensitive element 41 may also determine when the
readout circuit is to process the output of the reaction
sensing means. This is accornplished by suitable circuitry,
to be described, which analyzes the response of the photo-
sensitive element 41 as the test device 10 moves through the
beam from light source 37, causing a light-to-dark-to-light
cycle which is repeated for each of the test reagent areas.
With such circuitry the read command is given with the
blocking of the beam from light source 37 to photosensi-
tive element 41.
The timer 21 is connected to a test sequence selector
35 via path 36. Selector 35 interprets the signa~ received
from the code sensor 19 via path 20 and identifies the test
device 10 to a function generator 29 via path 28. Function
generator 29 is connected to module 23 via path 24. The
calibrate and amplify module 23 include~ a gating circuit
controlled by test sequence selector 35 via path 27 to allow
only the signals originating from the test reagent areas to
reach function generator 29.
The signal output of function generator 29 is trans-
mitted to a decoder 31 via path 30, said decoder also being
connected to the test sequence selector 35 via path 34.
The decoder 31 processes the output signals rom the func~
tion generator 29 and instructs a printer 33 via path 32
to give a visual quantitative representation of the readout
from function generator 29.
Referr~ng now to Figures 3a to 3f, the following is
;, 30 a de~ailed description of how code block 17 of Figures 2
and 4 functions as a code means for test device 10. In its
:
` '
- 14 -
~ ~7 ~ ~
1 start position as shown in Figure 3a, table 43 is position-
ed such ~ha~ the ligh~ beam emitting from fiber optics 40 in
no ~ay impinges thereon and simply strikes photosensitive
element 41. A test device 10 is contacted with a test fluid
and placed on table 43 as shown in Figure 3a. Actuator 45
(not shown in Figures 3a to 3e) then moves table 43 and test
device 10 in the direction shown by the arrow in Figure 3a
to their extreme le~tward position shown in Figure 3b. In
this position the light beam passes through the transparent
film 16 and glass table 43 and again impinges upon photo-
sensitive element 41.
Upon reaching this position the actuator 45 is reversed
and appropriate electronic circuity associated with photo-
sensitive elements 41 and 38 activated, and the table 43 and
test device 10 commence movement in the direction of the
arrow shown in Figure 3b. As the table 43 and device 10
move across the light beam, code block 17, whlch is highly
reflective and preferably white, in position P4 ~see Figu~e
1~, interrupts the light impinging upon-photosensitiv~ ele-
,
ment 41 and re1ects light back to photosensitive element
38 as shown in Figure 3c. The amount of light reflected
, back to photosensitive element 38 is used to calibrate the
instrument, as will be described hereinafter, and interrup-
tion of the light beam striking photosensitive element 41
is interpreted by ~he instrument electronics as representing
a block in position P4 ~See Figure 1).
The device lO continues movement in the direction shown
in Figure 3d and ~he light beam again strikes element 41
upon the passage of block 17 therethrough. C~ntinuing light
striking element 41 when the device 10 is in position P5 is
~' interpreted by the instrument as no block present in this
~, .
- 15 -
,`
~ .
' ' . :'. '' : ..
~737~
1 position and the instrument records this fact. Continuing
movement of device 10 causes reagent block 18a in position
P6 ~Figure 1~ to interrupt the light beam. It will be
assumed for purposes of explanation that the reagent in this
block has specifically responded to the pH of the fluid
being tested to give a chromogenic change. The ligh~ re-
flected back from block 18a varies according to the pH of
the test fluid. This is received by photosensitive element
38, and the resultant signal is processed as will be ex-
` 10 plained hereinafter. The device 10 continues its travel~
moving block l~a beyond the ligh~ beam so that it again
passes through tra~spaTent ~ilm 16 and glass table 43 and .,
'- stri~es photosensitive element 41 as shown in Figure 3f.
Continued movement of table 43 causes this procedure to 4e
repeaked with respect to blocks 18b and 18c, which will be
assumed for purposes of explanation to have respectively
responded to protein and blood in the test fluid, af'ter
which the table,43 and device 10 return to the noTmal staTt-
ing position shown in Figure 3a.
It will be appreciated that the initial movement of
the table 43 and device 10 in the direction shown in Figure
3a can be accom,plished by manual movemen~ thereof as opposed
to a motor drive.
Considering Figures l, 2 and 3a to 3f, the logic for
the coding of the device and instrument can be desc~ibed as
follows: The test device starts its travel with the light
beam at position P-0. If the photosensitive element 41
senses that the light beam is interrupted by an opaque area
in position P~l, and if it subsequently senses that the
~,~ 30 light beam is int~rrup,ted by an opaque area at position P-2
the test sequence selector 35 makes the decision that the
- 16 -
.:
,............. : ,
~ \ .
~ 7 ~
1 test device being read is test device number l shown în
Figure 1. Accordingly~ the electronics of the instrument
are programmed to read pH, protein, glucose, ketone, bili-
rubin, occult blood and urobilinogen test reagent areas, in
~hat order, as the device being read moves successively
through positions P-2 to P-8 to stop at position P-9. If,
on the other hand, the instrument does not see an opaque
area until the device being read reaches position P-6 and at
position P-7 senses another opaque area, the sequence selec-
to~ 35 identifies the device being read as device 14, and
the instrument is programmed to read glucose and protein as
the device moves successively through positions P 7 and P-8
to stop position P-9.
The opaque code block 17 may have ~wo functions: one
is for identifying the particular test de~ice to the instru-
ment as p~eviously described, and the other is to calibrate
the instrument Calibration is performed by the reaction
sensor 38 looking at the calibration block 17 sampling the
reflected light and converting the reflected l-ight level
into electrical signals used to standardize the electronic
circuitry pre-programmed for each of the test devices.
The following is a description of a speci~ic embodi-
ment of the present invention. It will be appreciated that -
this is merely exemplary and that numerous changes can be
made therein.
With reference to Figure 4, the system is initially
calibrated for use by inserting a first test device such
'~ as for example strip 1 in Figure 1, which has been dipped
into a zero calibra~ion solution and ~hereafter inserting
a second test device which has been dipped into a high posi-
ti~e solution~ wheTeby the system is calibrated to measure
.. ..... .. .
;37~
1 input reactions which fall within the ran~e selec~ed by the
use of the two calibration test de~ices. More specifically,
the first or zero calib~ation test device may, for example9
be dipped in a normal urine sample to thereby provide nega-
tive responses on each reagent b~ock thereof, and the second
or high positive calibratlon test device may be dipped into
solutlon such as a synthetic urine which provides ~he maxi-
mum high positive values foT each reagent block thereof.
More specifically, with placement of the zsro calibra-
tion test de~ice 10 on the table 43 and advancement of the
test device 10 to move the code block 17 into readout posi-
tion, photosensor 41 detects the code block 17 and provides
suitable signals o~er path 42 to the code sensor circuit 19.
The code sensor circuit 19 in a more basic embodiment may
comprise a simple stepping switch which advances one count
~! as each of the successive blocks is mov~d into readout posi-tion. In such arrangement, the count output of the counter
in the sensor 19 in effect represents a position on the
test device, Thus, if each of the reagent a-reas shown in
test device 1, Figure 1, has the same assigned posi~ion on
. each strip, the count output will therefore identify such
reagent.
I In a more sophistic~ted embodiment, the photosensor
means 41 may comprise a plurality o sensors which electroni-
cally or mechanically detect which one of the strips shown
' in Figure 1 is being processed, and in such event the count
' output from the code sensor 19 will represent correspond-
~` ingly different reagents for the different test devicesO For
~` the purpose of convenience the more basic embodiment is
described hereinafter.
- 18 -
.
. , ~ . . . .
.
~,
~ ~7 ~3
l With continued movement of the test device 10 to move
the first reagent block, such as 18a, beneath the read head,
the light beam is reflected back to photosensor 38 which,
via path 22, provides an output signal which has a value re-
lated to the amount of light reflected by reagent block 18a.
As shown in Figure 4 the resultant signal is fed to the in-
put of a voltage controlled oscillator 5~ of ~he calibratç
and amplify circuit 23 for translation into an output signal
whlch will vary in frequency from approxlmately 10 to 100
KHz with the value o~ the voltage of the signal inpu~ ~here-
to by photosensor 38
The frequency output o~ voltage controlled oscillator
50 is fed through gate S2 under the control of the output
signal from sequence control circuit 54 via path 27. In ad-
dition, as the block 18a is moved into position, the light
beam is interrupted, and a read si~nal is output by photo-
sensor 41 over pa~h 42 to the input of a code sensor circuit
19. ' :
Sequence control circuit 54 via path 64 inputs a sig-
nal to ~imer 21 which responsively provides a signal for 1/10
of a second over path 70 and path 27 to gate 52, enabling
the same to gate, or a period of 1/10 o~ a second, the out-
put signal of the voltage controlled oscillator 50, the
latter sign~l representing the amount of light reflected by
i
~he reagent block 18a.
The frequency signal output o gate 52 as applied over
.;~ conductor 72 is fed to a counter 74, which in one embodiment
comprised a pair of logic circuits, commercially available
as 74197, serially connected to effect the division of the
~ 30 frequency signa~ output by a factor of 256. The output
: of coun~er 74 is fed to a zero register 78 over path 76.
. - 19 -
', '
~ 7 ~7~
1 Thus, for a gated period of 1/10 second, the zero register
78 will count the pulses output from counter 74 which repre-
sent the amount of reflected light from the first reagent
block of the zero calibration test device.
- At the end of 1/10 of a second readout period~ the
timer 21 removes the timing signal from path 70 and sequence
circuit 54.removes the gating signal from gate 52 to termi-
nate the signal input to counter 74 and register 78. In
addition, sequence circuit 54 via load path 80 enables the
eight bit count which exists on the output of the zero regis-
ter 78 to be transferred to a buffer register 82. The same
load signal from sequence circuit 54 is also fed oveT con-
ductor 80 to the load input of a memory circuit 84 to cause
the parallel transfer of the eight bit output of buffer reg-
ister 82 into a first section of a memory 84 which has been
I preassigned to store the zero calibration word. The zero
. word fo~ the fiTst reagent block has now been stored in
memory 84. Bufer register 82 may comprise ~wo logic cir-
cuits, commercially available as 741979 having ~heir eight
. 20 bit input parallel connected to the eight bit output of the
¦ zero register 78, and memory circuit 84 may comprise a pair
of 7489 devices which have their eight bit inputs parallel
I connected to the eight bit outputs of buffer register 82.
: ! It will be apparent that as the actuator 45 causes the
1 25 table 43 to sequentially advance the blocks on the carrier
strip into ~he readout position, the systcm will operate to
provide a zero word in the corresponding section of memory
84 for use in the testing of unknown blocks. In one embodi-
ment, up to seven diffe~ent types of reagent blocks may be
included on the various strips, and accordingly the memory
84 was provided with the capacity to store eight different
- 20 -
,:
~ 7~'.3
1 words to represent the zero value for the eight differen~
reagents, and eight different words which rep~esent the high
positive value for each such reagent.
A test device which has been dipped into the high -
positive solution is now placed on the carrier for the
purpose of providing a word input into memory 84 which
i represen~s ~he high positive value or each of the reagent
; blocks such as 18a, 18b and 18c on the test device 10.
i As the start button 44 is operated, and actuatoT 45
advances code block 17 to the readout position, the code
sensor circuit 19 operates to provide output signals over
path 60 to identiy to the system the particular test device
being processed.
Photosensor 41 in detecting the entry of the block
18a into the readout position outputs a read signal via
path 42 to cause the code sensor 19 to output a signal via
path 20 to the sequence circuit 54 which outputs a signal
over path 86 to the load input of zero register 78. As a
result, the parallel bit output of the first zero word in
; 20 memory 84 is input to ~he zero register 78. Memory 84
outputs the complement of the number stored in memory 84
over path 102, and as a result, the input to the zero regis-
ter 78 is the 256 comple~ent of the number which was stored
in memDry 84 in the zero calibration step~ As will be
shown, the purpose o the transfer of the complement of the
zero calibration word to the zero registe~ 78 effects sub-
traction o the value represented by such word from the high
positive calibration signal which is to be now provided.
.~, . .
, - 21 -
.
-
~ . : ., . , - . , - . . .
:~4737~
l That is, with the advance-of block 18a into the readout
position photosensor 38 detects the light ref~ected and
outputs over path 22 to the.voltage controlled oscillator
50 a signal having a value related to the a~ount of re-
$1ected light. The output of the voltage controlled oscil-
lator 50 is gated to counter 74 for l/10 of-a second under
the control of timer 21 and sequence circuit 54 in the
manner heretofore described. Counter 74, in turn, outputs
a pulse to the zero ~egister 78 fOT each 256 input pulses,
which signals represent the high positive ~alue in the
calibration step for the first block 18a.
As the signals are input to the z~rs r~gister 78 as
a result of the inputting of a word ~epresenta~ive.of the
high positive value for the first block 18a, the zero
~ 15 register 78 is serially clocked from the value o~ the comple- ment signal stored therein toward the total count capacity of the registe~ 78 (count 255 in the present example). The
input signal over path 76 after count 255 is reached in
¦ ; register 78 results in an empty signal output oveT pa~h 90
to the clock input of a flip-flop circuit 92. Flip-flop
circuit 92, vîa the Q output and path 94, enables a gate 96
, I
to gate the signals output from voltage controlled oscilla-
tor 50 to the clock input on a divider register 100 via p.ath
1 98.
: ! 25 Digressing briefly, and by way of example, assuming. reagent block 18a is responsive to pH, and that the zero
, . ,
count represented by the word stored in memory 84 as a
result of zero calibration was a numerical value of 20, and
.. that the numerical value of the word stored in memory 84to represent the high positive value was 200, the complement
input to zero register 78 is 256 minus 20 or 236 at the
~ - 22 -
`:
.. . .
~737~)
1 start of the count input during the high positive readout
for reagent block 18a. As the signals are now input over
path 76 to the ze~o register 78 during the high positive
c~llbration, the count advances from the complement input
236, and as the count is advanced by the pulse inpu~ over
path 76 to a count of 256, a pulse over empty conductor 90
to the ~lip-flop 92 causes the further pulses output from
the voltage controlled oscillator 50 to be fed ove~ gate
96 and path 98 to the divideT register 100.
The divider register lO0 may be a pair of logic cir-
cuits, commercially available as 74197, which are serially
connected to the output path 98 and which therefore outputs
a pulse over path 104 in response to each 256 counts input
over path 98. .The signal output over conductoT 104 after
each 256 counts input to divider register 100 is fed to a
one-shot clrcuit 106, which is of the type commercially
available as a 74121, the output of which is connected over
path 108 to the clock input of buffer register 82. The
. buffer register 82 thus acts as a counter for the high posi-
: Z0 tive value minus the zero calibration value as divided by
. 256.
- As the test device is advanced to bring successive
ones o~ the reagent blocks 18b and 18c. (etc.) beneath the
.~ readout position, successive high positive eight bit words
25 . ` are stored in memory 84 to indicate the high positive value
for each of the different reagent blocks of the test device.
Summarily, at this. time memory 84 includes up to seven
words which represent the zero value of each of the reagents
.which is to be tested, and the seven words which re~resent
the high positive value of each of the reagents to be
tested.
.
~ 3 -
,. ~ : ' . -,
1 Digressing briefly at this time, reference is made to
a read only memory 110 which is a device commercially
available as an IM 5600 and which is preloaded for use with
the different thresholds of each of the reagents. More
specifically, with reference to the Table shown below, it
will be seen that a pH test block may have five differen~
reaction ranges respectively represented by correspondingly
different counts output by the divider register 100 (i.e.,
counts 0-255). The read only memory 110 is preloaded in a
known manner to indicate the discrete thresholds for each of
the different reagents. Thus, in a typical example, the
first pH reaction range is shown to be 0-2, the second pH
reaction range is shown to be 3-44.
,, .
I TABLE
, j . ~ - .
1 15 ~ Decode Points aRange)
i
0-2
6 3-44
7 45-128
8 129-213
9 214-25S
As the read only memory 110 is addressed by the
system in a manner to be shown, it w ll output the 256 com-
plement of the threshold indicated over path 114 to a de-
coder 112 for the purpose of comparison with the signals
input thereto by the divider register 100 in a manner to be
described.
, I
I Returning now to the readout of the unknown reagent
blocks o~ a test device, as the device is placed on table 43
and the code block 17 is advanced to the readout position,
~; 30 the photosensor 41 provides an output signal to code sensor
19 over path 42, and, over path 60, sensor 19 provides an
ID signal to an access register 116, which identifies the
particular str;p being processed. As the actuator 45
- Z4 -
'.,
~ ~ 7 ~ ~
1 advances the table 43 to move the first reagent block 18a
with the unknown reagent into readout position, code sensor
19 provides a signal over path 60 to the access regis~er
116 which identifies the reagent block which is being read
out.
As noted above, in a less complicated arrangement code
sensor 19 may comprise a simple s~epping device which ad-
vances one word as each ~eagent block is detected, and the
reagent blocks on thç test device in the present example
will be represented by ~he cou,nt output of the stepping
device over path 60 ~i.e. code block 17 would be 00~ reagent
block 18a would be 001, reage~t block 18b would be 002,
etc.). The access rqgister 116 in reponse to the count
signal over path 60 provides a ~hree bit word to a buffer
counter 121 which identifies the particular reagen~ block
being processed ~in the present example, 001 to identify the
pH reagent block 18a).
The three bit signal output of access register 116,
which identifies the particular reagent block belng pro-
' ' cessed, is also fed out over path 120 to a coincident cir- '
cuit 122. Assuming that the printer 128 ~which may include
a conventional stepper print wheel with the desired charac-
ter reading thereon) is ln a positi.on other than pH5, the
signal output from the printer fed over path 130 to coin-
cident circuit 122 w~ll be different from that fed over
path 120, and coincident circuit 122 thereupon responsively
`, provides a signal output over path 124 and an OR gate 126
to the stepping input of the printer 128 to cause the
printer ~o advance until such time as the desired position
tpH5) is reached. At that time the signal input from the
:
.~
~.,
.. . ; ~ . . . . .
~ ~ ~ 7 ~ 7 9
1 printer on path 130 and the signal input over pa~h 120 from
the access register will be coincident and the signal output
over path 124 will be removed to terminate the stepping of
the printer 128.
Returning to the readout position, as block 18a is
moved into the readout position, the read sign~l over path
42 from photosensor 41 via code sensor 19 and sequence cir-
cuit 54 is operated a~ before to enable gate 52 to gate the
signal output of the vol~age controlled oscillator 50 over
path 72 to the counter circuit 74 and over path 76 to the
zero register 78.
As before, sequence circuit 54 is also operated with
receipt of the read signal to output a load signal over
path 86 to cause thç complement of the zero calibration
value for the first reag~nt block (18a) to be fed over path
102 to the zero regi$tçr 78.
In addition, while a read signal over path 42 indicates
that a reagent block is m the readout position, sequence
circuit 54, via the access input to memory 84, is also
operative to advance the memory 84 one more access step to
cause said memory to output the corresponding span word for
: the pH reagent to the divider register 100.
With the complement of the zero calibration value from
the pH reagent now in the zero register 78 and the high posi-
tive value now in divider register 100, and timer 21 oper-
ated as before describe~ in response to the read signal out-
put ~rom photosensor 41~ the output signals of the voltage
con~rolled oscillator 50 are gated over gate 52 and the des-
; cribed path to the zer~ register 78. Zero register 78
counts up from the zero calibration value (which in ~he
: present example was 236~ in the direction of the total
- 26 -
.
: . . . . . -
`gL737~
1 count 256 of the register. As c~unt 255 is reached, ~he
following count over path 76 causes the zero r~gister 78 to
provide an output signal over path 90 to flip-flop 92 to
cause the output ~f the ~oltage controlled oscillator 50 to
S be gated through g~te ~6 ~ the divider register 100 over
path 98.
The divider: regis~er 100, as noted above, registers the
complement of the high positive value, and the signal input
over path 98 drives the divider register 100 from such value
to count 256 ? whereupon register 100 outputs a signal over
path 104 to the one shot circuit ~06 and ove~ path 132 to
the.clock input o~` ~he decoder register 112.
It will be recallcd that-the access register 116 on
path 118 and bu$fer 121 caused the complement of the first
threshold (See Table~ for the p~ reagent which was loaded
, I into read only memory 110 to be output over path 114 to
the decoder register 112. Accordingly, as the clock inputs
¦ are received over pàth 132 3 the decodeT register 112 ad-
vances from the complemçn~ for threshold 2 (25~ in the
present example), and a~ s~ch~time as the total count of
- , , ~ .
256 is reached9 the signal over conductor 134 to a one shot
circuit 136 resul~$ in an output signal over path 138 to
.
ll buffer 140 which, PV~ path 142, causes printer 128 to ad-
:: ~ vance one step.
:~
. 25 Bu~fer 140 a~$orb$ ~he count output from the one shot
circuit 136 which is~:oper~tive at a much higher rate than
the printer device 128,. That :is, as seen in the Table, the
pH reagent may ha~e as m~ny as five thresholds, and in the
event that signals representing the highest value threshold
are input over path 132 to the decoder register 112 9 the
buffer may store as many as five counts before the printer
- 27 -
. '` ' ' .
,
67~
1 128 is advanced to represent the change of threshold. The
buffer 140 outputs the s~ored signals over conductor 142 and
OR gate 126 to the step inpu~ of the printer 128 to cause
the wheel to advance over the successive steps. At such
time as the buffer 140 is empty, a signal over empty conduc-
'tor 146 is fed tD the ha~mer input of the printer 128 to
cause the printer to printout the value to which the printer
wheel has been advanced by the output signals of buffer 14G.
- All of the circuits, wi~h the exception of the access
regis~'er 116 and ~he low calibration and high calibration
value set in memory 84 are reset as each block is advanced
into,the readout position by reason of the detection there-
of by photosensor 41 and the signal supplied therefrom to
the code sensor 19 and sequence control 54. Accordingly,
the system is oper,atlve with e.ach successive readout of a
reagent block to compare such ~alue with the threshold
values stored in ~hç.read only memory 110 and to provide an
output signal which,controls the printer 128 to provide a
printout of such infor~ation.'
-, .
~XAM~L~
- This Example describes the preparation o ~he device
14 shown ln Figure 1~ Such test devices are for quanti-
: tatively determining p.rotein and glucose in bi.ological
fluids such as urine.
Pre~aration o~ Pro~ein Test Rea~ent
Sheets of Eatma~ an~ Dikeman No. 6Sl filter paper,
approximately 10 cm square, were saturated with the follow-
, ing solution: ''
- 28 -
~ ~ 7~ ~
1 ~.2 parts of 2M aq~eous s~dium cltra~e)
) 100 ml
7.8 paTts o~ 2M aqueous citric acid
Tetrabromophenol blue (0.08 weight)
) 100 ml
in 95% ethanol
To~al Volume ~00 ml
The wet sheets were dried at 100C for 15 minutes,
and further cut lnto squares O . 5 cm x O . 5 cm.
Preparation of Glucose Tes~ Rea~ent
Shee*s af Eatman and Dikeman No. 641 filter paper
were saturated wï~h the following solu~ion:
Sodium Alginate 5, O g
Polyoxyethylene Sorblt~n
Mon~oleate Wetti~g Age~t
(1% solubion) S0.0 ml
Gelatin 12.0 g
o-Tolidine~2HCi 2.5 g
Buffer (p~ ~,8 - 5.0, consisting of
citric acld 22,2 g/300 ml and
sodium citr~te 9q.8 g/300 ml~ 300.0 ml
.
Glu~o$e.. Oxidas~ 18.2 g
Peroxidase (hqrs,eFadish) 380.0 mg
95% Btha~p~ 125.0 ml
The sheets were dried a described abo~e ln the protein
test preparation and cut into 0.5 cm squares.
. . ' .
- Preparation of Test Devices
Tran~parent polysty~ene film approximately 0.0254 cm
thick was cut into strips 8.2 çm long by 0.5 cm wide.
~, .
Squares of prptein test reagent paper prepared as above
were attached ~o;one end of each strip. Squares of glucose
. test reagent papers were attached to the plastic strips
::~ spaced apprQximately 2 mm inwardly from the protein test
.
- 29
'',
:,
- - :
73~
1 squares. Blallk squares of white paper 0.5 cm square were
then attached to the strips spaced approximately 2 mm in-
wardly from the glucose test squares. Alternatively white
opaque areas m~y be printed on the test strips in place of
the white paper squares. The result was test device 14 as
shown in Figure 1.
USE OF THE TEST DEVI CBS
.
A test device as prepared above is momentarily dipped
into and removed from a urine test fluid, and the excess
fluid remove~ from the device by shaking. Prior to contact
with the test fluid, the protein test reagent area is a
yellow color. Upon contacting protein in the fluid, the
color changes from yellow (negative) to a bluish green (over
1000 mg %), depending upon the amount of protein in the
fluid. The results are reported in the following increme~ts:
negative ? trace, 30 mg % (~), 100 mg % (++)
300 mg % t~ and over 1000 mg % ~
The glucose test reagen~ area is a red color prior to
contacting the test fluid and changes to a deep purple upon
contacting glucosç in saîd ~luld. The results are reported
as negativç, small, moderate and large.
Upon remoral of the excess fluld from the test devic~
'I the start switçh 44 of the test instrument is depressed
. .
and the test d,evice 14 is plaeed in ope~ative position on
the table 43 of the test inst~ument. The test device 14
~;l moves wi~h the table ~3 ~hrough the light beam ~rom position
" P-O toward positio~ P~9. W~en the device 14 reaches posi-
tion P-6, thç light bea~ i5 interrupted by code block 17 and
~' the light is thereupon re~lected from this white code block
back to de~ector 38, to cause the instrument to be auto-
' ~ ~ ~
..
.~ .
. ~ -- - . , , ; . . ,
7~7~
1 matically calibrated by means of the calibrate module 23.
With continued movement of test device 14 the light beam is
a~ain interrupted by the gl~cose test area in position P-7.
The code sensor and re.ad signal module 19 in conjunc~ion
with test sequence selector 35 determines that the device
is a glucose-prot,ein,test device and the function generator
29 is advise~ ac~ordingly. When f,he light beam is centered
on the glucose test area, the read command is activated and
the decode to print ~odule 31 advises the printer 33 to
report the proper results ~rom ne~ative to large, depending
upon the amount o gl~cose in the urine test fluid. The
proçedure is repeated $o.r the protein test reagent when
, the light beam is centerçd on ~he protein test area in
; position P-8. Upon reaching position P-9, the actuator
45 returns the table 4~ to its Start position9 and the
instrument automatically shuts itsel~ off.
~.
' ' ~ " :
' ' :. .. :.,.
.~,.., -
', ,
: ' ,.
.
- 31 -
