U.S. patent number RE36,054 [Application Number 08/655,161] was granted by the patent office on 1999-01-19 for disposable cartridge for investigating physical properties of blood.
This patent grant is currently assigned to XYLUM Corporation. Invention is credited to Joseph Blake, Robert P. Cousineau, Mark I. Rosen, William C. Watson.
United States Patent |
RE36,054 |
Blake , et al. |
January 19, 1999 |
Disposable cartridge for investigating physical properties of
blood
Abstract
A disposable cartridge for measuring the physical properties of
blood is disclosed. A waste compartment supports a platform having
first and second syringe fittings. First and second syringes
containing blood samples to be measured are positioned within the
fittings. At least one testing station is located on the platform
for subjecting blood flowing from one of the syringes to a test
station, and the testing station is connected at a second end to
the waste compartment. Tests on blood running through each of the
blood channels may be conducted by inducing various platelet
activation conditions, such as piercing a channel, or putting a
platelet activating substance within a test channel. The cartridge
interfaces with a test stand which will measure pressure changes
within each of the test channels.
Inventors: |
Blake; Joseph (New Canaan,
CT), Cousineau; Robert P. (Mt. Kisco, NY), Rosen; Mark
I. (Hackensack, NJ), Watson; William C. (Greenwich,
CT) |
Assignee: |
XYLUM Corporation (Scarsdale,
NY)
|
Family
ID: |
25533289 |
Appl.
No.: |
08/655,161 |
Filed: |
May 30, 1996 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
Reissue of: |
987469 |
Dec 7, 1992 |
05316730 |
May 31, 1994 |
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Current U.S.
Class: |
422/73;
422/82.05; 422/82.13; 436/69; 436/70; 436/148; 600/368;
600/371 |
Current CPC
Class: |
G01N
33/4905 (20130101); G01N 11/08 (20130101) |
Current International
Class: |
G01N
11/00 (20060101); G01N 33/483 (20060101); G01N
33/49 (20060101); G01N 11/08 (20060101); G01N
011/04 () |
Field of
Search: |
;422/73,82.05,82.13
;436/69,70,148 ;128/637,638 ;73/64.41 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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0 129 425 |
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Dec 1984 |
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EP |
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WO 88/0211 |
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Mar 1988 |
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WO |
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Other References
Gorog et al. "Transient Effect of Aspirin on Collegen--Induced
Platelet Accumulation"--Amer. J. of Clinical Pathology, Sep. 1986,
vol. 86., No. 3 pp. 311-316. .
Kovacs et al., Hemostatic Evaluation in Bleeding Disorders from
Native Blood, A.J.C.P., Mar. 1989, vol. 91, No. 3, pp. 271-279.
.
Peters et al., Platelet hyperreactivity and inefficient spontaneous
thrombolysis in patients at high risk from an acute coronary event,
Cardiovascular Research, Jul. 1989, vol. 23, No. 7, pp. 567-572.
.
Gor,og, A New, Ideal Technique to Monitor Thrombolytic Therapy,
Aniology--The Journal of Vascualr Diseases, Feb. 1986, pp. 99-105.
.
Wagner et al., Local Thrombin Synthesis and Fibrin Formation in an
in Vitro Thrombosis Model. . . , J. Lab Clin. Med, Nov. 1990, pp.
636-650..
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Primary Examiner: Warden; Jill
Assistant Examiner: Carrillo; Sharidan
Attorney, Agent or Firm: Cushman Darby & Cushman
Intellectual Property Group of Pillsbury Madison & Sutro,
LLP
Claims
What is claimed is:
1. A disposable cartridge for measuring .[.the.]. properties of
blood comprising:
a waste compartment for receiving blood samples which have been
subject to measuring;
a platform supported on said waste compartment including first and
second fluidic couplings.Iadd., .Iaddend.which receive .[.the.].
front tip.Iadd.s .Iaddend.of first and second syringes which
contain blood samples, .[.connecting.]. .Iadd.wherein said fluidic
couplings connect .Iaddend.said platform and syringes together.[.,
forming.]. .Iadd.to form .Iaddend. a leak-proof assembly, said
fluidic couplings providing a pressurizing fluid to said syringes
and .Iadd.each .Iaddend.having an outlet for delivering pressurized
blood;
.Iadd.first .Iaddend.guide means for supporting said syringes in
alignment with said fluidic couplings;
first and second blood-carrying tubes mounted along a routing path
on a surface, connected to each of said outlets;
a punching mechanism comprising:
a ram operated punching needle, said needle being positioned during
a punching operation by a .Iadd.second .Iaddend.guide .Iadd.means
.Iaddend.to punch an opening in said first blood carrying tube,
permitting blood to exit through said opening;
a first domed chamber receiving .[.the.]. .Iadd.an .Iaddend.end of
said first blood-carrying tube, and receiving a .Iadd.first
.Iaddend.pressurizing fluid from a .Iadd.first .Iaddend.source of
pressurizing fluid .[.for.]..Iadd., said receipt of said first
pressurizing fluid .Iaddend.displacing air through a restricted
orifice, .[.and for.]. .Iadd.said first source of pressurizing
fluid .Iaddend.providing a pressure transducer connection which
measures changes in blood pressure occurring during a flow of blood
through said first blood-carrying tube into said first domed
chamber, .Iadd.said flow of blood .Iaddend.displacing .Iadd.first
.Iaddend.pressurizing fluid through said restrictive orifice into
said waste compartment; and
a second domed chamber receiving .[.the.]. .Iadd.a .Iaddend.distal
end of said second blood carrying tube, and receiving a
.Iadd.second .Iaddend.pressurizing fluid .[.for.]. .Iadd.from a
second source of pressurizing fluid said receipt of said second
pressurizing fluid .Iaddend.displacing air through a restricted
orifice in said second domed chamber, .[.as well as.]. .Iadd.said
second source of pressurizing fluid .Iaddend.providing a connection
to a pressure transducer for measuring changes in blood pressure in
said second blood-carrying tube from blood flowing through said
.Iadd.second .Iaddend.domed chamber.Iadd., said blood flow
.Iaddend.displacing .Iadd.said second .Iaddend.pressurizing fluid
through said restrictive orifice into said waste compartment.
2. The disposable cartridge of claim 1 wherein said second
blood-carrying tube contains a platelet-induced body.
3. The disposable cartridge of claim 1 further comprising a
vertically extending conduit connected to said fluidic couplings
which is received in said syringes, and supplies said pressurizing
fluid to said syringes.
4. The disposable cartridges of claim 3 wherein said guide means
position said syringes to be tangential to a rear edge of said
cartridge so that said syringes can be located against a common
heating surface.
5. The disposable cartridge of claim 1 further comprising a tapered
chamber having an axis aligned with said punching needle, said
chamber tapered to receive an optical sensor for detecting blood
exiting from a punched hole in said first blood-carrying tube.
6. The disposable cartridge of claim 5 wherein said tapered chamber
includes an inlet for receiving a saline solution which washes
blood from said hole punched in said first blood-carrying tube.
7. The disposable cartridge of claim 1 wherein each of said first
and second blood-carrying tubes .Iadd.are supported .Iaddend.in a
common plane to permit said tubes to be heated by a heating
surface.
8. An apparatus for measuring the properties of blood
comprising:
a disposable cartridge including first and second supports for
vertically supporting two blood-filled syringes, in first and
second fluidic couplings forming a sealed assembly therewith, said
couplings having inlets for receiving a pressurized fluid, and
outlets for supplying blood .[.and.]..Iadd., and said disposable
cartridge further including .Iaddend.first and second testing
channels for carrying blood from said outlets, and a waste
receptacle for receiving tested blood from said first and second
testing channels; and,
a test stand for receiving said cartridge, said test stand having a
heater for maintaining said blood-filled syringes at a constant
temperature, and including means for maintaining plungers
associated with said syringes in a fixed position when said
disposable cartridge is receiving a pressurizing fluid, and a ram
which operates a punching needle at a constant speed for punching a
hole having a precise diameter in one of said testing channels.
9. The apparatus of claim 8 wherein said test stand further
comprises a second heater for maintaining said first and second
testing channels at a constant temperature.
10. The apparatus of claim 9 further comprising an optical sensor
support for maintaining an optical sensor positioned with respect
to a bleeding chamber in one of said testing channels.
11. The apparatus of claim 9, wherein said test stand further
provides a connection between a bleeding chamber centrally
positioned with respect to said .[.channel hole.]. .Iadd.punching
needle .Iaddend.and a source of saline solution.
12. The apparatus of claim 8, wherein said test stand includes a
source of pressurizing fluid coupled to said fluidic coupling
inlets when said cartridge is received in said test stand.
13. The apparatus of claim 12, wherein said test stand includes
first and second pressure transducers which measure the blood
pressure in said first and second testing chambers.
14. A disposable cartridge for measuring physical properties of
blood comprising:
a waste compartment supporting a platform, said platform having at
least one fluidic coupling, and having
a guide for positioning at least one syringe holding a blood sample
into said fluidic coupling which forms a sealed assembly
.[.therewith.]. .Iadd.with said syringe.Iaddend.;
at least one testing station.Iadd., .Iaddend.located on said
platform.Iadd., .Iaddend.for subjecting blood flowing from said
syringe to a testing condition, and connected .Iadd.to said waste
compartment .Iaddend.to discharge tested blood in .Iadd.to
.Iaddend.said waste compartment; and
conduit means connecting said at least one syringe to said testing
station.
15. A disposable cartridge according to claim 14, wherein said
testing station comprises means for creating a precise opening in
said conduit means to simulate bleeding.
16. A disposable cartridge according to claim 14 further comprising
a second syringe having a blood sample.Iadd., said second syringe
.Iaddend.forming a sealed assembly with said cartridge.Iadd.,
.Iaddend.and a second testing station which includes a flow channel
connected to said second syringe having a blood sample .[.which
includes.]..Iadd., said flow channel including .Iaddend.a blood
platelet activating substance.
17. The disposable .[.apparatus.]. .Iadd.cartridge .Iaddend.of
claim 14 further comprising a conduit extending through said
fluidic coupling along an axis of said syringe, and connected to
receive a pressurizing media.
18. The disposable cartridge of claim 14, wherein said test station
further comprises a columnar pressure chamber having a volume of
fluid immiscible with blood which is displaced by said blood, and
which is connectable to a pressure transducer for monitoring
pressure resulting from blood flowing into said columnar pressure
chamber.
19. The disposable cartridge of claim 14 wherein said testing
station includes means for introducing a shear force to blood
flowing in said channel, thereby activating blood platelets.
Description
The present invention relates to disposable devices for making
measurements of the physical properties of blood. Specifically, a
cartridge has been designed which is especially useful in
conducting experiments on native, non-anticoagulated blood.
In the treatment of various blood disorders, it has been necessary
to make measurements on whole, native blood to assess the formation
of platelets and the adequacy of haemostatic functions of the blood
before embarking on specific medical procedures for patients having
these disorders. Further, other disorders such as myocardial
infarction, stroke, thrombolysis or blood dissolution properties,
must be monitored and assessed repeatedly following recovery to
prevent recurrence of a blood clot.
Techniques for measuring the physical attributes of platelet
activation, all of which is related to the foregoing disorders,
have been the subject of numerous investigations. The difficulty in
making such measurements lies in the difficulty to collect native
whole blood which has not been anticoagulated and conduct
experiments which do not induce any platelet activation except
under very controlled circumstances. In investigating the behavior
of native whole blood, a device for performing in vitro haemostasis
on native whole blood, is described in EPO Application No. 129425.
This patent describes a laboratory technique which is capable of
simulating bleeding. A fresh supply of native blood is connected to
a polyethylene tube. A flow of blood is started through the tube
and bleeding is simulated by establishing a hole in the tubing of a
known diameter. The bleeding which occurs through the hole is
monitored, both optically and through a pressure measurement of the
flow of blood.
A further improvement of this technique is described in a later
International Patent Application PCT/GB87/00633, having an
international filing date of Sep. 10, 1987. In this patent,
multiple channels of blood flow were established, and concurrent
measurements of haemostasis were made in each of the blood flow
channels. This permitted a control channel having blood drawn at
the same time, thus having substantially the same chemical
composition to be measured and compared to each other.
The laboratory technique set forth in the above-referenced patent
documents requires a fairly high level of skill on the part of the
personnel conducting such tests. Further, as blood is known to
carry viruses, including the deadly HIV virus, it is necessary that
personnel always take precautions to avoid contact with the
blood.
A disposable blood-handling cassette is described in U.S. Pat. No.
5,047,211 which will permit such tests to be carried on in
accordance with the preceding patent documents, while isolating
medical personnel from coming in contact with the blood under test.
The device, which is completely self-contained, includes multiple
reservoirs which receive a blood sample for carrying out the
experiments and investigation of blood, as set forth in the
previously identified patent documents.
Further investigation of these techniques have demonstrated how the
handling of blood, even in a disposable cartridge can result in
platelet activation before any testing begins. The process of
extracting blood from a human donor in itself can activate
platelets which interfere with the investigation of blood under
controlled conditions.
It has also been found that further control over punching holes in
a blood-carrying tubing is necessary in order to provide for
repeatability between tests of succeeding samples of blood.
SUMMARY OF THE INVENTION
It is an object of this invention to provide for a disposable
cartridge which can be used to carry out tests on blood.
It is a more specific object of this invention to provide for a
disposable cassette which may be used in haemostasis and
thrombolysis measurements, and which effectively isolates infected
blood samples from users of these devices.
It is yet a more specific object of this invention to provide a
device which is designed to avoid inadvertent platelet activation
in a sample of blood under test.
These and other objects of the invention are provided by a
disposable cartridge which is capable of conducting tests on whole
blood. The cartridge is designed to introduce a minimum amount of
disturbance to the blood's physical properties, and specifically to
avoid platelet activation through handling of the blood samples.
The cartridge creates an in vitro environment which models the
circulatory system with regard to temperature and flow. In doing
so, shear force experienced by the blood is accurately controlled.
In this way, platelet activation is maintained under control until
tests are performed on the blood. The device therefore permits the
simulation of normal circulatory blood conditions, as well as
simulating a disease environment or injury during testing.
In carrying out the invention, the disposable cartridge
incorporates a totally isolated compartment for tested blood which
will preclude any inadvertent contact with medical personnel. The
compartment supports a platform which includes at least one
receptacle for receiving a blood sample vessel such as a syringe.
The use of the syringe as the blood .Iadd.sample .Iaddend.vessel
avoids the platelet activation which occurs when transferring the
blood from a syringe used to draw the blood from the human donor to
a reservoir in another test device. Further, the syringe which acts
as a blood sample vessel is exposed to a heating plate of a test
stand for maintaining the blood sample vessel at a constant
temperature, which improves the control over experiments being
conducted.
In accordance with the preferred embodiment of the invention,
experiments are conducted with two blood samples contained in two
syringes. The first blood sample is used in a test channel to
simulate bleeding. The second blood sample is used in a second test
channel to simulate the effect of a platelet-activating substance
contained in the test channel of the two-channel device on blood
flowing through the test channel.
The first of the channels provides for a flow of blood through a
punching station, which forms an accurately-defined opening in the
blood tube to simulate bleeding. A pressure chamber is provided
which contains a volume of immiscible fluid. Blood exiting the test
channel enters its own pressure chamber where it displaces the
volume of immiscible fluid through an orifice into a waste
compartment. A test stand associated with the disposable cartridge,
provides a fluidic connection between the pressure chamber and a
pressure transducer. As blood flows through the test channel, the
immiscible fluid is displaced through an orifice generating
pressure within the pressure chamber. Changes in measured pressure
will provide an accurate monitoring of platelet activity. In
accordance with the preferred embodiment of the invention, the
bleeding chamber is filled with a saline solution. Drops of blood
exiting the punctured opening in the channel having a punching
station can be observed in the tapered end of the bleeding chamber
via an optical detecting device.
The second test channel provides for a second flow of blood from a
second syringe past a platelet-activating substance, into a second
pressure chamber. The second pressure chamber includes a volume of
immiscible fluid which is displaced through orifice into the waste
compartment. A second transducer measures the changes in pressure
within the pressure chamber as a measure of the platelet
activity.
DESCRIPTION OF THE FIGURES
FIG. 1 illustrates a test stand having a disposable cartridge in
accordance with the preferred embodiment of the invention for
measuring the physical properties of blood.
FIG. 2 illustrates a fluidic diagram of the first test channel
provided by the cartridge and test stand of FIG. 1.
FIG. 3 is a fluidic diagram of a second test channel provided in
the disposable cartridge and test stand arrangement of FIG. 1.
FIG. 4 is a first section view of the cartridge inserted in the
test stand.
FIG. 5 is a top section view of the disposable cartridge of FIG.
4.
FIG. 6 illustrates a second, section view of the cartridge
illustrating the pressure chambers which terminate each test
channel.
FIG. 7 illustrates another section view of the punching station
which pierces a precise hole in one of the test channels.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to FIG. 1, there is shown a disposable cartridge 11
in accordance with a preferred embodiment of the invention, which
is received within a test stand 10. The cartridge 11 supports a
pair of syringes 20, which contains native, non-anticoagulated
blood obtained from a donor. The cartridge 11 will provide for a
two-channel test device for measuring the properties of blood
flowing from each of the syringes 20 into first and second test
channels which terminate in a waste compartment. The cartridge 11
is completely disposable and includes two fittings for receiving
each of the ends of syringes 20. The assembly of the cartridge 11
and syringes 20, having two samples of blood from which
measurements of certain physical conditions of the blood are to be
made, are inserted into the test stand 10 during the performance of
tests on the samples of blood.
The test stand 10 includes a support .[.13.]. which is used to
position the cartridge 11 with respect to the test stand 10. The
support .[.13.]. is driven by a stepping motor 17 to move the
cartridge 11 against the heaters 21 and 29 of the test stand
10.
The test stand 10 supports two heaters 21 and 29. Heater .[.1.].
.Iadd.21 .Iaddend.will maintain each of the syringes 20 at a
preferred temperature to keep test conditions constant for all
blood samples being measured. The second heater 29 will maintain
the two test channels of the cartridge 11 carrying the blood under
test substantially equal to that of the syringes 20.
The cartridge 11 is arranged in accordance with the principles set
forth in the aforesaid patent documents so that an immiscible
displacing fluid is introduced into the syringes 20, displacing the
blood through the test channels. The displacing immiscible fluid is
supplied from a pair of reservoirs which are pressurized with air
and received through sealed coupling in the cartridge 11. Another
pair of sealed couplings are connected to a pair of conduits for
supplying a displacing fluid from another reservoir to each
pressure chamber which terminates the two blood channels. Following
filling of the pressure chambers with immiscible fluid, a pair of
pressure transducers connected to the pair of conduits monitor
pressure changes in each blood channel. Changes in flow due to test
conditions in each channel result in a pressure change which can be
accurately monitored.
The plungers on the syringes 20 are maintained in position during
pressurization of the syringes 20 with the immiscible fluid by a
retainer 23 which is connected to a linear actuator 25. Control
over linear actuator 25 will lower the retainer 23 to maintain the
plungers of each of the syringes 20 in their unpressurized
position. As the size of the blood sample may change, it is
necessary to have the retainer 23 adjustable to accommodate
different plunger heights.
In accordance with the principles set forth in the devices and
processes described in the aforesaid patent documents, a support
30, supporting an optical detector 28, is also provided. The
optical detector 28 detects blood which flows in a bleeding chamber
during a test conducted in one of the blood channels.
The two test channels which are provided by the system of FIG. 1,
are schematically illustrated in FIGS. 2 and 3. FIGS. 2 and 3
illustrate the fluid circuits which are provided by each of the
test channels in the cartridge device. FIG. 2 illustrates a test
channel wherein the process of platelet activation is monitored by
puncturing a blood-carrying channel 40 with a punching needle
assembly 43. The punching needle assembly 43 includes a guide and
needle which, when driven by the linear actuator 45, will pierce a
pair of precisely-positioned holes across a common diameter in the
blood carrying channel 40, at a controlled rate.
The blood-carrying channel 40 is connected to the receptacle 36 for
receiving the end of the syringe 20. The receptacle 36 also
includes a standpipe section 38 which is connected to receive,
through the sealed coupling member 37, a supply of immiscible
displacing fluid.
The blood channel 40 terminates in a pressure chamber 51. The
pressure chamber 51 also receives a volume of immiscible displacing
fluid from a second sealed coupling member 54, connected to another
source of displacing fluid.
Initialization of the test channel requires that air pressure from
pump 33 be forced through air regulators 34 and 57 to a pair of oil
supplies 32 and 56.
The pressure chamber 51 is filled and air expelled via an orifice
as the oil supply enters from valve 55 through the sealed coupling
member 54 of the cartridge. The orifice is provided by the tube 53
which is connected at one end to the domed pressure chamber 51 and
at the other end to the waste compartment 63.
As the volume of immiscible fluid is filling the pressure chamber
51, a similar column of displacing fluid is entering through the
flow regulator 35 and cartridge sealed coupling member 37. The
standpipe 38 is connected through the receptacle 36 to the sealed
coupling member 37, and permits the immiscible oil to enter the
syringe. The oil displaces the blood through the proximal end 44 of
blood channel 40.
Blood which flows through the channel 40 displaces the volume of
immiscible fluid contained in the pressure chamber 51 through the
orifice established by the tube 53, and into the waste compartment
63. The flow of blood thus established from the syringe 20 through
channel 40 represents an in vitro normal circulatory condition for
the blood. Platelet activation is minimized until the punching
operation commences which will simulate bleeding, resulting in a
state of high shear rate causing platelet activation.
Prior to operating the linear actuator 45 which drives the punching
mechanism 43, a saline solution is pumped from a supply 48, via
pump 47, through a coupling 50 into the bleeding chamber 42. The
saline solution which is heated in heater 46 fills the tapered
portion of bleeding chamber 42 and washes the exiting blood from
the hole punched in the blood-carrying channel 40. Care is taken to
maintain and regulate the temperature of the saline solution
constant.
The tapered portion of the bleeding chamber 42 is observable by the
optical detectors 28. As is set forth in the foregoing patent
documents, the duration of bleeding is detected by optical detector
28.
Once the pressure chamber 51 has been filled with the volume of
immiscible fluid, the valve 55 is closed, isolating the source of
immiscible fluid from the pressure chamber 51, leaving coupling
member 54 pressure transducer .[.0.]. .Iadd.60 .Iaddend.connected
to the pressure chamber 51. The pressure in this hydraulic circuit
formed from the syringe 20, blood-carrying channel 40 and pressure
chamber 51 will be monitored and various changes in the physical
characteristics of blood can be monitored by the pressure
transducer 60. Chief among these changes includes platelet
aggregation which results from shear forces on the blood exiting
the punched hole in the channel 40. Initially, blood exiting the
holes will be detected in a lowering of the pressure monitored by
pressure transducer 60. Further, an optical signal will be produced
as blood flows into the bleeding chamber 42. As the platelets
aggregate in the hole, the resulting pressure changes will be
monitored by the transducer 60. This change in pressure occurring
during the punching of the holes, as well as the subsequent
coagulation which occurs in the lumen of the tubes, will give the
clinician significant data regarding the condition of the blood
under test.
The second channel provided by the disposable cartridge is shown in
FIG. 3. Identical components for this second test channel are
marked with the identical reference numerals. The test channel of
FIG. 3 does not include a punching station for piercing the
blood-carrying tube 40. This channel can suffice as a control
channel and pressure changes noted by the transducer 60 are
accurately compared with the pressure transducer 60 of FIG. 2.
Additionally, a platelet-inducing substance 61 may be introduced
into the channel 40 of FIG. 3, and the downstream pressure measured
via the pressure transducer 60. This platelet-forming substance 61
may be a collagen substance, as described more particularly in the
aforesaid international patent application. Platelet activation
occurring from the substance 61 will result in a change in pressure
for the test channel. These events may be accurately monitored by
the pressure transducer 60, giving the clinician an opportunity to
compare pressure changes for different samples of blood in
different tests. The second test channel can also provide
information to interpret the data obtained from the first channel.
The initialization of the test channel is the same as that of FIG.
2, wherein the pressure chamber 51 receives a volume of immiscible
fluid, while the syringe 20 receives, through standpipe 38, a
similar volume of immiscible fluid.
In both devices, the outlet tubes 53 for the pressure chambers are
connected to the waste compartment and displaced immiscible fluid
enters the waste compartment and is securely maintained within the
cartridge. The displacement of the immiscible fluid through the
orifice created by the outlet tubes 53 creates a pressure which is
monitored by the pressure transducer 60. Thus, flow conditions are
accurately monitored as long as the flow through the orifice
continues. It should be noted that the punched holes in tube 40 of
the first channel will reduce the flow into pressure chamber 51,
dropping the monitored pressure. When the blood totally clots,
pressure drops to zero since there is no flow. The optical
monitoring provided by optical detector 28 will detect any
expulsion of a platelet plug from the punched holes. At the
conclusion of the tests, the entire cartridge with connected
syringes may be disposed of safely.
Having generally described the tests carried out by the test stand
10 and disposable cartridge 11, a more detailed description of the
disposable cartridge will now be made.
Referring now to FIG. 4, there is shown a partial section view of
the cartridge 11, as viewed from the test stand which receives the
cartridge 11. The cartridge 11 includes a waste compartment 63
supporting on the top surface thereof a platform 62. Those
components shown in FIG. 4 can be made of a plastic material
through injection molding or similar processes.
The platform 62 supports a pair of studs 24, each of which receives
the flared ends of the syringe receptacles 36. The studs 24 support
the standpipes 38 which are coaxial with the axis of the
receptacles .Iadd.or hydraulic couplings .Iaddend.36. The end of
the receptacles 36 which receives the front tip 22 of each of the
syringes 20 has a luer fitting taper to provide a force fit, tight
against any blood or pressurizing fluid leakage.
The stud 24 for each of the test channels includes a .[.fluidic.].
.Iadd.factor .Iaddend.coupling member 37, which may be an
elastomeric substance which is pierced by an injection needle or
pointed cannula from the test stand 10. Displacing fluid is
received through the coupling member 37 and supplies the immiscible
displacing fluid through the standpipes 38 into the body of the
syringes 20.
Each of the pressure chambers 51 extends through the platform and
have domed portions 69 which are connected to the outlet tubes 53
which provide an orifice. Displacing fluid for the pressure
chambers 51 is received through the couplings 54, which also may be
of an elastomeric insert, pierced by a needle or pointed cannula
supplying the displacing fluid. A similar fluid coupling is
provided at 50 for injecting a saline solution into the bleeding
chamber 42.
Each of the blood-carrying tubes 40 for each test channel is
supported on a surface 39. Surface 39 is positioned so that in use
it touches the heater 29, thereby maintaining constant the
temperature of the blood-carrying tubes 40. The receptacles 36 and
studs 24 are also positioned such that each of the syringe bodies
20 is located within the heater 21.
The blood carrying tubes 40 have a routing path which is initially
straight down, and then routed upward. A collagen substance 61 is
shown introduced in one of the blood carrying tubes which is by the
radius of the blood carrying tube.
A top cover 67 is fixed to the platform .[.64.]. .Iadd.62
.Iaddend.and includes a pair of guide holes .Iadd.20 .Iaddend.which
support the syringes 20 in alignment with the receptacles .Iadd.or
hydraulic couplings .Iaddend.36. .Iadd.Guides 70 position the
syringes tangential to the rear edge of the cartridge so that the
syringes can be located against a common heating surface.
.Iaddend.The cover 67 also includes a hole 66 which receives the
ram 68. Ram 68 is advanced by the linear actuator 45 towards the
punching mechanism 43 at a controlled speed to control the shape of
the hole being formed.
The section view of FIG. 5 illustrates the test channels. The test
channels include the bleeding chamber 42, as well as the
platelet-activating substance 61. Also shown is an outlet 72 for
the saline solution which enters via the coupling 50 to fill the
bleeding chamber 42.
Details of the cartridge punching station 43 are shown more
particularly in FIGS. 6 and 7. The punching station includes a
plunger 80 which slides within a sleeve 77. A guide 75 having a
forked end positioned over the blood-carrying tube 40 is connected
to the sleeve 77. A centrally-located needle 76 is connected to
move with the plunger 80 when the ram .[.62.]. .Iadd.68 .Iaddend.is
accelerated against the surface 83. The end of the needle 76 is
located within a through-hole in the forked end. The forked end
positions the needle tip in line with the inner diameter of the
blood-carrying tube 40.
The plunger 80 moves inside the sleeve 77, pushing the needle
through the hole in the guide 75, and pierces opposite sides of the
blood-carrying tube. A detent on the plunger 80 moves between a
first notch 79 and second notch 81 in the sleeve 77. As the ram 82
pushes plunger 80 against the force of a spring 82 when the ram is
retracted, the spring 82 withdraws the plunger 80, the needle 76
and guide 75. The result is a pair of holes in the blood-carrying
tube 40, which permits bleeding to occur in the bleeding chamber
42. The elastomeric material 83 at the top of the plunger seals the
cartridge against leakage.
The blood profusing from the hole drains via the tapered section 71
with the saline solution into the waste compartment 63, where it is
captured. Other waste material from the pressure chambers 51 also
exit via the drain tubes 53 to the waste compartment 63. The level
of saline in the bleeding chamber 42 is controlled by the rate at
which saline is introduced, and the height of the exit port 73. The
level of saline is maintained at a level which insures washing of
the holes punched in the blood-carrying tubes.
The foregoing structure of the cartridge provides for a minimum
disturbance to blood samples which are to be tested under very
controlled test conditions. By using the syringes as the reservoir,
the inadvertent activation of platelets in the test sample are kept
to a minimum. Further, the entire cartridge is designed such that
the blood sample throughout the test channel can be maintained at a
constant temperature, thus minimizing the effects of temperature
differentials on each test being conducted. Once the test is
completed, the motor 17 of FIG. 1 can be reversed and by grasping
the handle 74 of the cartridge, the entire cartridge with connected
syringes may be disposed of without risk of contamination to any of
the testing personnel.
As the cartridge can be made from any suitable plastic material,
the costs can be maintained at a minimum, while insuring safety to
those carrying out such tests.
Thus, there has been described with respect to one embodiment, an
example of the invention. Those skilled in the art will recognize
yet other embodiments defined more particularly by the claims which
follow.
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