U.S. patent number 3,912,455 [Application Number 05/395,214] was granted by the patent office on 1975-10-14 for apparatus for clinical laboratory sample collection and automatic sample processing.
Invention is credited to Eric S. Lichtenstein.
United States Patent |
3,912,455 |
Lichtenstein |
October 14, 1975 |
Apparatus for clinical laboratory sample collection and automatic
sample processing
Abstract
A semi-automatic disposable device of flexible material for
receiving a fluid sample and particularly a blood sample,
subdividing it into aliquots for sequential processing in
conjunction with contained active principles, or reagents, to
perform multiple, predesignated analytic procedures. The necessary
sequential manipulations are controlled by external means operating
through pressurizable passages in said device.
Inventors: |
Lichtenstein; Eric S. (New
York, NY) |
Family
ID: |
27380418 |
Appl.
No.: |
05/395,214 |
Filed: |
September 7, 1973 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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108118 |
Jan 20, 1971 |
3774762 |
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157942 |
Jun 29, 1971 |
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Current U.S.
Class: |
422/430; 422/73;
206/569; 600/575; 600/579; 600/578 |
Current CPC
Class: |
A61M
1/16 (20130101); A61M 1/1668 (20140204); F04B
43/06 (20130101); A61M 1/1696 (20130101); A61M
2205/123 (20130101); A61M 2205/125 (20130101); A61M
2205/126 (20130101); A61M 2205/3306 (20130101); A61M
2205/6018 (20130101); A61M 1/1656 (20130101) |
Current International
Class: |
A61M
1/16 (20060101); F04B 43/06 (20060101); G01N
033/16 () |
Field of
Search: |
;23/23R,253R,259,592
;206/47A,223 ;128/2F,2G |
References Cited
[Referenced By]
U.S. Patent Documents
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3476515 |
November 1969 |
Johnson et al. |
3497320 |
February 1970 |
Blackburn et al. |
3689224 |
September 1972 |
Agnew et al. |
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Primary Examiner: Serwin; R. E.
Attorney, Agent or Firm: Blum, Moscovitz, Friedman &
Kaplan
Parent Case Text
CROSS REFERENCE TO RELATED APPLICATIONS
The present application is a continuation-in-part of my co-pending
application Ser. No. 108,118, Filed: Jan. 20, 1971, now U.S. Pat.
No. 3,774,762 and Ser. NO. 157,942, Filed: June 29, 1971, now
abandoned.
Claims
I claim:
1. A disposable device for receiving blood or other fluid and
physiological samples and carrying out diagnostic tests on said
samples, comprising two main sheets, at least one of which is of
thin flexible plastic, said main sheets being sealed together in a
distribution system pattern including junction means for joining
said distribution system to blood-taking means for receiving blood
therefrom, a first chamber for receiving and holding a blood sample
or fluid derived from said blood, a first channel connecting said
first chamber to said junction means, a second chamber for holding
a diagnostic test reagent, said second chamber incorporating a
breakable seal through which said test reagent may be released by
application of pressure, pressure means for breaking the seal on
said second chamber, a third chamber for receiving said blood
sample and said reagent on breaking said seal, further channels
connecting said first and said second chambers with said third
chamber and first valve means for controlling the flow of blood or
fluid from said first chamber to said third chamber, said valve
means comprising at least a third sheet of flexible plastic sealed
to one of said two main sheets to form a pressurizable valve
passage crossing said channel connecting said first and third
chambers, whereby pressurizing said pressurizable valve passage
results in closure of said channel connecting said first and third
chambers.
2. The disposable device as defined in claim 1 wherein said
distribution system comprises pluralities of first, second and
third chambers, where said pluralities are not necessarily equal in
number, a manifold header connected to said junction and a branch
channel leading from said header to each of said first
chambers.
3. The disposable device as defined in claim 1 further comprising
second valve means of structure similar to said first valve means,
said second valve means being disposed so that it lies across the
channel from said junction to said first chamber to control flow of
blood to same and to prevent back flow of blood from said first
chamber.
4. The disposable device as defined in claim 1 wherein said
pressure means is a compartment and a pressurizable passage
connected thereto, said compartment overlying a first chamber, said
compartment and pressurizable passage comprising a sheet of
flexible plastic sealed to at least one of said two main sheets of
said distribution system, said one sheet being flexible, whereby
pressurizing said compartment while one of said valve means at a
channel connected to said first chamber is unpressurized causes the
blood in said first chamber to be essentially completely expelled
in a corresponding direction, the combination of a valve in each of
two channels connected to a first chamber and a pressurizable
compartment having the characteristics of a two-way pump.
5. The disposable device as defined in claim 4, wherein said
compartment spans and overlies corresponding first and second
chambers, and said breakable seal in said second chamber is
positioned at the junction of said second chamber with its
connecting channel so that pressurizing said compartment while said
valve in said channel leading to the corresponding third chamber is
unpressurized results in breakage of said seal and simultaneous
transfer of said blood and reagent to said third chamber where
reaction can occur.
6. The disposable device as defined in claim 4 wherein said
compartment spans and overlies said first and second chambers, and
said device further comprises a bag of flexible plastic and test
reagent therein, said bag having a seal breakable by application of
pressure in said compartment so that pressurizing said compartment
while said valve in said channel leading to the corresponding third
chamber is unpressurized results in breakage of said seal and
simultaneous transfer of said blood and reagent to said third
chamber where reaction can occur.
7. The disposable device as defined in claim 5, wherein each of the
channels leading from said first and second chambers to the
corresponding third chamber has an orifice of selected size therein
whereby the relative rates of flow of blood and reagent to said
third chamber can be controlled.
8. The disposable device as defined in claim 1 wherein a branch
channel leading to a first chamber has therein a filter of
controlled porosity for removal of unwanted suspended solid
matter.
9. The disposable device as defined in claim 8, wherein said branch
channel has therein between said filter and said header a porous
plug impregnated with a reagent for reacting with one or more
components of blood passing therethrough to form solid matter, said
solid matter being removed from the resultant fluid by said filter
as said fluid passes therethrough.
10. The disposable device as defined in claim 1, wherein one of
said main sheets is essentially rigid.
11. The disposable device as defined in claim 4 wherein both of
said main sheets are flexible and at least one of said valves of
said pressurizable compartments are formed of two additional sheets
of flexible plastic, one of each being sealed to opposite sides of
said main sheets, whereby a channel or a chamber may be subjected
to pressure from both sides of said main sheets.
12. The disposable device as defined in claim 11, wherein at least
one compartment spanning a chamber spans both faces of said chamber
and a portion of said two main sheets exterior to said chamber by
the use of two additional plastic sheets sealed to said main
sheets, and that part of said two main sheets exterior to said
spanned chamber and interior to said compartment is apertured,
whereby a fluid held at a predetermined temperature may be passed
through a pressurizable passage into said compartment on one face
of said distribution system, through said aperture and out through
the corresponding pressurizable passage on the opposite face of
said distribution system, as a means of bringing a blood sample or
a reagent or both to a predetermined temperature.
13. The disposable device as defined in claim 1, further comprising
a terminal block, and at least one channel leading from one of a
first and third chamber to an edge of said distribution system,
said terminal block being clampable to said edge of said
distribution system and having a recess therein at a position
corresponding to said one channel leading to said edge, whereby
said terminal block provides a closure to said one channel and
simultaneously a recess for receiving fluid from a first or a third
channel.
14. The disposable device as defined in claim 13 wherein at least
one portion of the wall of said recess is of a soft, self-sealing
material so that it may be penetrated from the exterior of said
block by a hollow needle for taking of fluid from said recess.
15. The disposable device as defined in claim 13 wherein a
transparent vessel is held in said recess, said vessel being in a
position to receive fluid from said distribution system and the
wall of said recess is so apertured to make it possible to pass a
light beam through said vessel and fluid contained therein.
16. The disposable device as defined in claim 1, further comprising
a terminal block clampable to an edge of said distribution system,
said distribution system having a pressurizable passage having an
open end at said edge of said distribution system, said terminal
block having an aperture therethrough in registry with said open
end of said passage, said terminal block further having connecting
means for making a fluid-tight connection between said passage and
said aperture and between said aperture and an external source of
fluid under pressure.
17. The disposable device as defined in claim 12, wherein both of a
pair of compartment passages connected to one compartment have an
open end proximate but not at an edge of said distribution system,
said pair of compartment passages are in registry with each other
on opposite faces of said main sheets, said distribution system
further comprises a pair of hollow, resilient half-cylinders
positioned in said open ends of said compartment passages to hold
same open, and said device further comprises a terminal block
adapted for clamping to said edge, said block having a matched pair
of apertures therethrough, and a pair of first connecting means for
connecting each of said apertures to one of said compartment
passages and a pair of second connecting means for connecting one
of said apertures to a pressurized source of fluid and the other of
said apertures to a sink.
18. The disposable device as defined in claim 4 wherein said
compartment spans and overlies said first and second chambers and
said device further comprises a sealed bag containing reagent, said
sealed bag being within said second chamber and having a region
weak enough so that pressure exerted by said compartment can
rupture said bag, thereby forcing said reagent toward said third
chamber through a channel connecting said second and third
chambers.
19. The disposable device as defined in claim 4 wherein said
distribution system includes three channels two of which lie on
either side of a central channel, and a tube connecting said two
channels and crossing through said central channel, said tube
having an aperture proximate either end and passing through said
central channel without fluid interconnection therebetween, thereby
making it possible to connect two channels across a central channel
for sensing pressure or other characteristics of fluid in said
central channel without changing the composition of said fluid.
20. The disposable device as defined in claim 1 further comprising
a pair of electrodes sealed into at least one of a channel or
chamber for measuring the electrical conductivity thereof.
21. The disposable device as defined in claim 1 further comprising
conductive metal on either side of a channel for measuring the
capacitance of the fluid therein.
22. The disposable device as defined in claim 1 further comprising
at least one one-way valve means in a channel for preventing
back-flow of blood or fluid.
23. The disposable device as defined in claim 11 wherein said main
sheets and two additional sheets are sufficiently flexible to
permit rolling said device into a cylinder for storage in a
container.
24. The disposable device as defined in claim 1 wherein said third
sheet is essentially coextensive with said main sheets.
25. The disposable device as defined in claim 4 wherein said third
sheet is wide enough only to form said passages and said
compartment, said third sheet being sealed to one of said main
sheets in the formation of said passages and compartment.
26. A disposable device for taking fluid from a patient and for
carrying out diagnostic tests on said fluid, comprising valves,
ducts, reservoirs and pumps, at least part of said valves, ducts,
reservoirs and pumps being formed of a first pair of flexible
plastic sheets joined together in a first pattern including
interconnected ducts and chambers, and inlets and outlets for
connecting said ducts and chambers with exterior sources of fluid
and drains and at least a third flexible plastic sheet joined to
said first pair in a second pattern such that at least one
pressurizable channel between said third sheet and said first pair
of sheets crosses a duct between said first pair of sheets,
pressurization of said channel serving to close said duct at said
crossing of said duct and said channel, the combination of duct and
channel thereby functioning as a valve, said second pattern further
being such that a pressurizable region between said third sheet and
said first pair of sheets overlies a chamber between said first
pair of sheets, said chamber having an input duct and an output
duct connected therewith, pressurization of said region serving to
expel liquid through one of said input and said output ducts when
said one duct is functioning as a valve, whereby the combination of
said pressurizable region with said chamber and said pressurizable
channel with said duct functions as a pump.
Description
BACKGROUND OF THE INVENTION
In a recent analysis of the efficiency of a highly automated
clinical laboratory it was estimated that despite the automation,
40% of the cost of procedures was for labor associated with
preparation of samples for automatic processing. This analysis
included all steps subsequent to collection of a specimen, and did
not include costs of supplies.
IN ADDITION TO THE COSTS INCURRED IN THE CLINICAL LABORATORY
ITSELF, THERE ARE COSTS ASSOCIATED WITH TRANSPORTING THE SPECIMEN
FROM WHATEVER SPECIMEN-COLLECTING MEANS ARE USED, TO THE CLINICAL
LABORATORY. Particularly, where the specimen is a blood sample, it
is necessary that the sample be treated immediately to prevent
deterioration. This involves further labor, frequently on the part
of a physician or surgeon taking the specimen, so that the costs
incurred may be very substantial even before the sample reaches the
clinical laboratory.
In view of the above considerations, it would be highly desirable
that a disposable device be available where the device could be
operatively joined to a sample-taking means and where the device
could then, either automatically or semi-automatically put the
specimen into a stable form and then, preferably, carry out as many
of the desired clinical tests as can be arranged for.
Above all, it would be desirable that the equipment used in
conjunction with the sample-taking means be sufficiently
inexpensive so that it is economical to use it only once, and be
sufficiently compact so that it can readily and conveniently be
used in combination with a sample-taking means and can be stored in
a small volume such as a rectangular box.
Substantial progress toward these objectives has already been
reported. For instance, Johnson et al., U.S. pat. No. 3,476,515
have described a pouch-like container consisting essentially of two
sheets of flexible plastic bonded together so as to form
compartments including reagent chambers in which reagent is stored
and reaction chambers in which reaction with a reagent takes place.
Fluids are transported through the Johnson et al device by means of
pressure applied externally. The means of applying pressure are not
specifically disclosed but apparently such means are primarily
mechanical.
Blackburn et al., U.S. Pat. No. 3,497,320 disclose a system in
which reagents for specific tests are prepackaged in individual
disposable containers; the system need not be preprogrammed and a
complex apparatus is required to bring into position the particular
chemical reagent desired for the particular specimen.
Bednar et al., U.S. Pat. No. 3,504,376 have developed an automatic
chemical analyzer which also uses packages of individual reagents
which are brought to the specimen in accordance with the particular
program of tests designed for the specimen. Again, complex
equipment is required, only the reagent packages being
disposable.
Auphan et al., U.S. pat. No. 3,607,097 have developed an apparatus
which automatically transports a plurality of liquid samples such
as blood, through a series of program steps for colorimetric
analysis of the samples. The equipment is complex, requiring a
plurality of conveyors, and needles and tubes must be provided for
taking samples from one set of containers and transferring them to
another.
As can be seen from the above references, considerable effort in
the direction of automatic or semi-automatic analysis of
physiological specimens and in particular, blood specimens has been
expended. Nevertheless, it is apparent that devices for carrying
out a variety of biochemical tests which are essentially automatic
and which are inexpensive enough so that they may be disposed of
after one use remain to be developed, or at least, substantially
improved.
SUMMARY OF THE INVENTION
A semi-automatic or automatic disposable device for receiving blood
or other physiological fluid specimens and carrying out diagnostic
tests on same is formed of two main sheets at least one of which is
flexible sealed together in a pattern including a junction through
which a sample is received and channels leading to compartments for
temporary storage of samples, for storage of reagents and for
reaction between samples and reagents. Samples are transported
within the two main sheets by a combination of pumps and valves
formed of at least a third sheet sealed to one of said two main
sheets. Said third sheet is sealed to said one of said two main
sheets in a pattern having compartments overlying said sample
chambers and reagent chambers and also having passages which can be
pressurized. Some of said passages overlie said channels so that
pressurizing such passages closes off said channels thereby acting
as valves. Other passages are connected to said compartments making
it possible to pressurize said compartments and expel fluid or
reagent from respective chambers between said two main sheets.
Filters may be inserted in channels leading to said fluid passages
for the purpose of removing unwanted solid matter. Further, plugs
containing reagents, such as for clotting blood, may be placed
upstream of said filters so that the product emanating from said
filters is serum.
One edge of said device may be enclosed in a block adapted for
making connection with said pressurizable passages. Also, said
block may be adapted for holding cuvettes into which fluid may be
transferred for examination by spectrophotometric or other similar
means. One face of said block may be of a self-sealing material
such as rubber so that fluid samples may be withdrawn by means of a
hypodermic needle.
The device may be fitted to any blood-taking means such as a
syringe, a branch tube of a circulating system such as is used for
dialysis or a catheter.
Accordingly, an object of the present invention is an improved
disposable device suitable for semi-automatic or automatic
operation for carrying out diagnostic tests on fluids.
Another object of the present invention is an improved disposable
device suitable for semi-automatic or automatic operation for
carrying out tests on blood or other physiological fluids.
A further object of the present invention is an improved disposable
device suitable for semi-automatic or automatic operation which can
be formed of thin flexible plastic and which can be rolled up into
a small space for storage.
An important object of the present invention is an improved
disposable device suitable for semi-automatic or automatic
operation which can be coupled with a computer for a print-out of
results.
Yet another object of the present invention is an improved
disposable device suitable for semi-automatic or automatic
operation which can be coupled to external equipment for
programming a desired sequence of tests.
A significant object of the present invention is an improved
disposable device suitable for semi-automatic or automatic
operation in which a combination of pressurizable passages and
compartments formed of flexible plastic can serve as valves and
pumps.
Still other objects and advantages of the invention will in part be
obvious and will in part be apparent from the specification.
The invention accordingly comprises the features of construction,
combinations of elements, and arrangement of parts which will be
exemplified in the constructions hereinafter set forth, and the
scope of the invention will be indicated in the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
For a fuller understanding of the invention, reference is had to
the following description taken in connection with the accompanying
drawings, in which:
FIG. 1 is a plan view of a device in accordance with the present
invention coupled to a syringe;
FIG. 2 is a view taken along the line 2--2 of FIG. 1;
FIG. 3 is a view taken along the line 3--3 of FIG. 1;
FIG. 3a is a view taken along line 3a--3a of FIG. 1;
FIG. 4 is a sectional view of a terminal block connecting
pressurizable passages with a source of pressure;
FIG. 5 is a view taken along 5--5 of FIG. 4;
FIG. 6 is a view taken along the line 6--6 of FIG. 4;
FIG. 7 is an exploded view in perspective of a modification in
which a connection is established between two passages lying on
either side of a third passage;
FIG. 8 is a view taken along the line 8--8 of FIG. 7;
FIG. 9 is a sectional view of a fluid channel having electrodes
therein for the measurement of electrical conductivity;
FIG. 10 is a sectional view of a fluid channel enclosed in
conductive plates for the measurement of capacitance;
FIG. 11 is a sectional view of a one-way flap-valve;
FIG. 12 is a schematic view of a hypodermic needle in a vein in an
arm for taking blood therefrom;
FIG. 13 shows schematically how the device of the present invention
is connected for taking blood from tube through which blood is
circulating;
FIG. 14 is a view of the device of the present invention rolled
into a spiral and inserted into a rectangular box;
FIG. 15 is a plan view of a pressurizable passage using at least a
third sheet of plastic in combination with two main sheets where
the third sheet is not co-extensive with said main sheets;
FIG. 16 is a sectional view taken along the line 16--16 of FIG. 15;
and
FIG. 17 is a sectional view of a reagent chamber containing an
easily-rupturable bag holding said reagent.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
a portion of a device in accordance with the present invention is
shown in plan in FIG. 1 and is indicated generally by the reference
numeral 21. A principal portion of the device 21 is body 22
consisting principally of two main sheets 23 and 24 (FIG. 2) which
are sealed together in a pattern including channels 26, fluid
chambers 27, reagent chambers 28 and reaction chambers 29. In FIG.
1 main body 22 is shown connected to syringe 31 at junction 32. In
order to take blood, for instance, from a subject, hollow needle 33
is inserted into a vein in the usual manner as shown in FIG. 12 and
plunger 34 is withdrawn from the barrel of the syringe, drawing
blood or other fluid into the syringe. In the syringe shown in FIG.
1 the plunger has a central tube 36 which connects with junction
32.
Device 21 is normally supplied in collapsed form but any residual
air or other gas may be drawn into the plunger as the plunger is
withdrawn from its seat in the barrel of the syringe. Optionally a
one-way valve, indicated by the dashed circle 37 may be built into
central tube 36 to prevent drawing any residual gas into the
syringe.
After filling the syringe to the desired level, the plunger is once
more forced toward its seat in the barrel of the syringe. As a
result, the fluid in the syringe flows through the central tube,
and the one-way valve if present, into the channels in the body 22
of the device. Conveniently, the channel arrangement is such that
blood flows first into a manifold header 38 and thence into branch
channels 26a.
In traversing branch channel 26a unwanted solid materials suspended
in the fluid may be removed by positioning a filter 39 in branch
channel 26a. Also, pretreatment of the fluid as by contact with a
clotting agent may be carried out by positioning a porous plug 41
impregnated with a clotting agent upstream from filter 39. Another
important technique is inclusion of anticoagulant such as EDTA or
stabilized heparin in porous plug 41 or a fluid chamber 27. Main
sheets 23 and 24 are preferably flexible and transparent, although
one of said sheets may be rigid. The sheets must be sealable either
by heat-sealing, ultrasonic welding or by adhesives. Suitable
materials are polyolefins, polyvinyl acetate, polyvinyl chloride,
polyvinylidene chloride and copolymers of such materials as well as
ionomers, polyethylene terephthalate and any other polymers which
are flexible, transparent and sealable by one means or another so
that channels for fluid flow therethrough may readily be formed in
desirable selected patterns. Where one of the two main sheets 23
and 24 is rigid, it may be made of acrylic or any other material to
which a flexible sheet can be sealed in a desired pattern. in
general, however, the use of two flexible sheets is preferable to
one sheet which is rigid and one sheet which is flexible.
Control of flow to the various fluid chambers 27 and reaction
chambers 29 is achieved by means of at least one additional sheet
of flexible plastic, sealed to a flexible main sheet. Preferably,
where both main sheets 23 and 24 are flexible, two auxiliary sheets
are used, one sealed to either face of the device. These auxiliary
sheets 42 and 43 can be seen in FIGS. 3 and 3a. In the process of
sealing auxiliary or control sheets 42 and 43 to main sheets 23 and
24, pressurizable passages 44, 45 and 46 are formed on both sides
of the device 22. Pressurization of passages 44 results in pinching
off branch channel 26a, a step which would prevent entry of fluid
into chambers 27. Depressurization of passages 44 allows fluid to
pass from header 38 through branch channels 26a into chambers 27.
Pressurization of passages 46 prevents flow of fluid from chambers
27 and 28 to reaction chambers 29. Depressurization of passages 46
allows flow of fluid from fluid chambers 27 and reagent chambers 28
to reaction chambers 29.
To induce flow of fluid into reaction chambers 29, a driving force
is necessary. This force is supplied by pressurization of passages
45, which, in turn, pressurize compartments 47, each of which spans
one or both of a fluid chamber and a reaction chamber. In the
design shown in FIG. 1, each compartment 47 spans both
chambers.
The method by which fluid is introduced into chambers 27 has
already been presented. As for reagent chamber 28, this chamber,
prior to use, is separated from passage 26 by means of a seal 48
which is weaker than the remainder of the periphery around the
chamber. In preparation of reagent chamber 28, one of the main
sheets is depressed as by vacuum-forming or the like, and the
desired reagent is introduced, in liquid form, into the depression.
The other main sheet is then sealed to the first main sheet using a
technique such that the seal between the chamber 28 and passage 26
is weaker than around the remainder of the periphery. The weakening
of the seal 48 relative to the remainder of the seal can be
effected by such means as using a smaller quantity of adhesive, a
weaker adhesive, or by using a lower pressure in this region during
heat-sealing of the two sheets together. An alternative method of
introducing and retaining reagent is shown in FIG. 17, in which an
inner bag 49, introduced into reagent chamber 28 during the process
of forming chamber 28, contains reagent. Bag 49 is deliberately
made of a weak material which is readily rupturable or may have a
weak spot in the bag which will break readily when compartment 47
is pressurized.
Auxiliary or control sheets 42 and 43 may be essentially
coextensive with main sheets 23 and 24. This is the form as shown
in FIG. 1. Alternatively, control sheets 51 and 52 (FIGS. 15 and
16) need be only wide enough for the formation of passages 44, 45
and 46 and compartments 47.
As is evident, by selective pressurization of passages 44 and 46
and compartments 47, it is possible to simulate the action of a
pump which can operate in either direction.
In order to carry out the pressurization of the various passages in
the control sheets and to make full use of the reactions which take
place in chambers 29, a terminal block 53 is attached to one edge
of the device. Outlet channels 26b leading from chambers 29 into
terminal block 23 are clamped between portions 54 and 56 of
terminal block 53 by clamping means such as screws 57.
Conveniently, a cuvette is fitted into terminal block 53 to receive
fluid transported through channel 26b. Cuvette 58 is preferably of
glass and light from a source 59 can be passed therethrough for
examination by a spectrophotometer or other optical instrument.
The way in which the pressurizable passages fit into terminal block
53 is shown in FIGS. 4 and 5. To hold the control sheets 42 and 43
firmly against the block 53, semi-cylindrical, hollow inserts 61
and 62 are placed in the end portions of passages 44, 45 and
46.
Pressure or fluid can be introduced into the pressurizable passages
by means of tubes 63 and 64 which lead to pressurizable passages on
either side of main sheets 23 and 24. For most purposes, such as in
driving or expelling the contents of chambers 27 and 28, pressure
is introduced through tubes 63 and 64. Another use for these tubes
is for thermostatting the contents of chambers 27 and 28. For this
purpose, compartment 47 is provided with an aperture 66 through
main sheets 23 and 24. Then, water at a controlled temperature can
be introduced through tube 63 into a passage 45 on one side of the
main sheets to enter compartment 47 surrounding chambers 27 and 28,
through aperture 66 to the other side of the main sheets and back
through passage 45, also on the other side of the main sheets, and
out through 64 to a sink (not shown).
The channels in main sheets 23 and 24 can be put to a variety of
uses. For instance, it is possible to bridge a channel 69 lying
between two channels 67 and 68 without leakage into channel 69. For
example, as shown in exploded form in FIG. 7 and in section in FIG.
8, tube 71 having apertures 72 and 73 therein makes it possible to
introduce fluid or gas into channel 67 and transport it to channel
68, passing through channel 69 in the process without leakage into
channel 69.
Other uses are shown in FIGS. 9 and 10. In FIG. 9 is shown a
channel 74 formed between sheets 76 and 77 by a sealing method,
with electrodes 78 and 79 in channel 74. Electrodes 78 and 79 have
leads 81 and 82 which penetrate sheet 76 and emerge at the exterior
surface thereof so that contacts can be made with brushes 83' and
84'. By use of this arrangement, the conductivity of the fluid in
channel 74 can be measured. Alternatively, either 78 or 79 could
represent a thermocouple by which the temperature of the fluid in
the channel is measured.
In the arrangement of FIG. 10, a channel 83 is formed by sealing
sheets 76 and 77 together. Metal foil or conductive paint is then
applied to sheets 76 and 77 in the form shown as indicated by the
reference numerals 84 and 85. Using brushes 87 and 88 making
contact with conductive members 84 and 85 the capacitance of the
fluid in channel 83 can be measured.
That section of block 53 through which section 2--2 is taken has
apertures or windows therein so that light may be shined through a
cuvette 58. However, channel 26b may terminate in a recess in block
53. Where this is the case, it is desirable that block 53 be made
of a self-sealing material such as rubber through which a
hypodermic needle can be inserted as at 91, so that a sample of the
material or fluid in chamber 29 can be withdrawn.
The form of the device as shown in FIG. 1 is particularly suitable
for compact storage. The device can be rolled up around the block
53, leaving junction 32 exposed, and inserted into a rectangular
box as shown in FIG. 14. This makes for economy in storage space
and makes it possible to keep the device sterile until it is ready
for use. As aforenoted, the device 21 can be joined to a syringe
31. Alternatively, it can be joined to a catheter (not shown) or to
a branch tube 93 on a main tube 94 through which blood or other
fluid is flowing.
Control of the direction of fluid flow can be achieved not only by
the combination of pressurizable compartments and passages but by a
one-way flap valve constructed as shown in FIG. 11. The flap valve
96 consists of two main sheets 97 and 98 which form a channel 99,
to the interior of which are sealed two curved sheets 101 and 102.
These sheets 101 and 102 end in flat sections 103 and 104 which
make contact with each other but are not sealed together. Liquid
flowing in the direction of the arrow forces the flat sections or
flaps 103 and 104 apart so that flow is permitted. Any attempt to
force liquid in the opposite direction forces flaps 103 and 104
together, cutting off or preventing flow.
A wide variety of measurements and tests are possible with the
embodiments of the device shown. For instance, reference numeral 78
in FIG. 9 could represent an ion-specific electrode for
determination of sodium, potassium, chloride, calcium, hydrogen or
magnesium. Using cuvette 58 it is possible to determine
colorimetrically bilirubin, cholesterol, uric acid, glucose, total
protein and albumin and phosphate.
Studies of kinetics and reaction rates can also be carried out.
Examples are the determination of enzyme levels, serum glutamic
acid, oxaloacetic acid, transaminase, other transaminases,
creatine-phosphokinase, lactic dehydrogenase, and phosphotase.
Further, determination of enzyme activity with respect to the rate
of reaction on a known concentration of substrate can be carried
out.
Other enzymatic reactions which may be carried out are treatment of
glucose with glucose oxidase and catalase in which hydrogen
peroxide is formed which then decomposes to give oxygen, and
decomposition of urea by urease to give gaseous ammonia, and
treatment of lactate with lactic dehydrogenase to release
detectable hydrogen ions.
Where reaction rates and kinetics are involved, it is desirable
that the reagent and the fluid to be reacted enter the reaction
chamber 29 at controlled rates. This can be effected by means of
suitably located orifices 106 in channels 26 (FIG. 1).
From the above, it can be seen that the device of the present
invention makes possible a sequentially-programmed series of
diverse reactions in an apparatus which is sufficiently inexpensive
so that it can be treated as disposable. Furthermore it can be used
in combination with a variety of bloodtaking means such as the
syringe of FIG. 1 in which blood flow from the syringe to the
device can be effected by the simple expedient of placing a plug
107 of a soft material such as soft rubber on the point of needle
33 and pushing plunger 34 towards the seat of syringe 31. Also, as
aforenoted, it can be used for tapping off samples of blood during
the process of dialysis to determine the degree of progress of the
process. Samples can easily be withdrawn for carrying out studies
for which the particular device is not designed. Further, it can be
coupled to equipment such as has already been described for
carrying out studies of any degree of complexity. These advantages
are gained largely by use of the combination of auxiliary sheets of
flexible plastic sealed to main sheets of flexible plastic in a
design which provides valves and pumps of a type not hitherto
available. Provision of the terminal block 53 then makes it
feasible to connect the pressurizable passages and compartments in
the control sheets with external sources of pressure, vacuum and
thermostatted fluid which are programmed as desired. Thermostatting
is particularly important where kinetics are involved. Furthermore,
the device is such that changes in pressure, conductivity,
capacitance, etc. can readily be followed and recorded.
Most important, the device can be coupled with auxiliary equipment
which supply test data, where such data is in the form of computer
print-out.
It will thus be seen that the objects set forth above, among those
made apparent from the preceding description, are efficiently
attained and, since certain changes may be made in the above
constructions without departing from the spirit and scope of the
invention, it is intended that all matter contained in the above
description or shown in the accompanying drawings shall be
interpreted as illustrative and not in a limiting sense.
It is also to be understood that the following claims are intended
to cover all of the generic and specific features of the invention
herein described, and all statements of the scope of the invention
which, as a matter of language, might be said to fall
therebetween.
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