U.S. patent application number 12/503665 was filed with the patent office on 2010-02-04 for cuvette-based apparatus for blood coagulation measurement and testing.
This patent application is currently assigned to International Technidyne Corporation. Invention is credited to Gregory M. Colella, Maria Figueroa, Henry D. Huang, Anthony F. Kuklo, JR., James A. Mawhirt, Dimitri V. Shishkin.
Application Number | 20100028207 12/503665 |
Document ID | / |
Family ID | 41550706 |
Filed Date | 2010-02-04 |
United States Patent
Application |
20100028207 |
Kind Code |
A1 |
Colella; Gregory M. ; et
al. |
February 4, 2010 |
CUVETTE-BASED APPARATUS FOR BLOOD COAGULATION MEASUREMENT AND
TESTING
Abstract
An apparatus for measuring blood clotting time includes a blood
clot detection instrument and a cuvette for use with the blood clot
detection instrument. The cuvette includes a blood sample
receptor-inlet; a channel arrangement including at least one test
channel for performing a blood clotting time measurement, a
sampling channel having at least one surface portion that is
hydrophilic, communicating with the blood sample receptor-inlet and
the at least one test channel, and a waste channel having at least
one surface portion that is hydrophilic, communicating with the
sampling channel; and a vent opening communicating with the
sampling channel. The sampling channel, the vent opening and the
waste channel, coact to automatically draw a requisite volume of a
blood sample deposited at the blood receptor-inlet, into the
sampling channel. More specifically, air compressed within the
blood clot detection instrument, the at least one test channel of
the cuvette, and the section of the sampling channel extending
beyond the vent opening of the cuvette, coacts with the waste
channel to cause a leading edge of the blood sample drawn into the
sampling channel from the blood receptor-inlet, to pull back within
the sampling channel and uncover an optical sensor in of the blood
clot detection instrument. The uncovering of the optical sensor
activates a pump module of the blood clot detection instrument,
which draws the requisite volume of the blood sample into the at
least one test channel.
Inventors: |
Colella; Gregory M.;
(Montclair, NJ) ; Huang; Henry D.; (Edison,
NJ) ; Kuklo, JR.; Anthony F.; (Bridgewater, NJ)
; Shishkin; Dimitri V.; (Whippany, NJ) ; Figueroa;
Maria; (Elizabeth, NJ) ; Mawhirt; James A.;
(Brooklyn, NY) |
Correspondence
Address: |
DUANE MORRIS LLP - Princeton
PO BOX 5203
PRINCETON
NJ
08543-5203
US
|
Assignee: |
International Technidyne
Corporation
Piscataway
NJ
|
Family ID: |
41550706 |
Appl. No.: |
12/503665 |
Filed: |
July 15, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61081290 |
Jul 16, 2008 |
|
|
|
Current U.S.
Class: |
422/73 ;
422/400 |
Current CPC
Class: |
B01L 3/502715 20130101;
G01N 33/4905 20130101; B01L 3/502723 20130101; B01L 2300/0864
20130101; B01L 2300/165 20130101; B01L 2400/0487 20130101; B01L
2300/027 20130101; B01L 2400/086 20130101; B01L 3/50273 20130101;
B01L 2300/0816 20130101; B01L 2200/146 20130101; B01L 2300/0654
20130101; B01L 2200/16 20130101; B01L 2200/12 20130101; B01L
3/502746 20130101 |
Class at
Publication: |
422/73 ;
422/102 |
International
Class: |
G01N 33/49 20060101
G01N033/49; B01L 3/00 20060101 B01L003/00 |
Claims
1. A cuvette for use with a blood clot detection instrument, the
cuvette comprising: a main body including: a blood sample
receptor-inlet; a channel arrangement comprising: at least one test
channel for performing a blood clotting time measurement; a
sampling channel communicating with the blood sample receptor-inlet
and the at least one test channel, at least the sampling channel
having at least one surface portion, a coating, an insert or liner,
and any combination thereof, that is hydrophilic; and a waste
channel communicating with the sampling channel; and a vent opening
communicating with the sampling channel, wherein the sampling
channel, the vent opening and the waste channel coact to
automatically draw a requisite volume of a blood sample deposited
at the blood receptor-inlet, into the sampling channel.
2. The cuvette of claim 1, wherein the coaction between the
sampling channel and the vent opening includes a force generated by
the at least one surface portion of the sampling channel that is
hydrophilic and which draws the blood from the blood sample
deposited at the blood sample receptor-inlet into the sampling
channel and venting of air through the vent opening which is
displaced from the sampling channel by the incoming blood.
3. The cuvette of claim 1, wherein the channel arrangement further
comprises a vent channel connecting the vent opening with the
sampling channel.
4. The cuvette of claim 1, wherein the channel arrangement further
comprises a member associated with the waste channel for delaying
the filling of the waste channel until the sampling channel is
filled.
5. The cuvette of claim 1, wherein the channel arrangement is
formed in a surface of the main body.
6. The cuvette of claim 5, further comprising a substrate for
closing and sealing at least a portion of the channel arrangement
formed in the surface of the main body.
7. The cuvette of claim 6, wherein the substrate forms the at least
one surface portion of the sampling channel that is
hydrophilic.
8. The cuvette of claim 6, wherein the substrate comprises a film
with a hydrophilic surface, the hydrophilic surface of the
substrate forming the at least one surface portion of the sampling
channel that is hydrophilic.
9. The cuvette of claim 6, wherein the substrate comprises a film
and a layer of hydrophilic material disposed on the film, the
hydrophilic material forming the at least one surface portion of
the sampling channel that is hydrophilic.
10. The cuvette of claim 9, wherein the hydrophilic material is an
adhesive which attaches the substrate to the main body.
11. The cuvette of claim 1, further comprising a blood clotting
reagent disposed in the at least one test channel.
12. The cuvette of claim 1, wherein the at least one test channel
includes a section having at least one textured surface.
13. The cuvette of claim 1, wherein the at least one test channel
includes a restriction.
14. The cuvette of claim 1, wherein the main body is made of one of
a hydrophobic material, a hydrophilic material, or a combination of
a hydrophobic material and a hydrophilic material.
15. The cuvette of claim 1, wherein the waste channel has at least
one surface portion, a coating, an insert or liner, and any
combination thereof, that is hydrophilic.
16. The cuvette of claim 1, wherein the at least one test channel
has at least one surface portion, a coating, an insert or liner,
and any combination thereof, that is hydrophilic or
hydrophobic.
17. The cuvette of claim 3, wherein the vent channel has at least
one surface portion, a coating, an insert or liner, and any
combination thereof, that is hydrophilic.
18. The cuvette of claim 4, wherein the member associated with the
waste channel comprises a jumper channel or a restriction.
19. The cuvette of claim 18, wherein the jumper channel or the
restriction has at least one surface portion, a coating, an insert
or liner, and any combination thereof, that is hydrophilic.
20. The cuvette of claim 1, wherein the channel arrangement further
comprises a jumper channel connecting the waste channel with the
sampling channel, the jumper channel for delaying the filling of
the waste channel until the sampling channel is filled.
21. An apparatus for measuring blood clotting time, the apparatus
comprising: A) a blood clot detection instrument, the blood clot
detection instrument comprising: a pump module; and at least one
pressure sensor; and B) a cuvette for use with the blood clot
detection instrument, the cuvette comprising: a main body
including: i) a blood sample receptor-inlet; ii) a channel
arrangement comprising: a) at least one test channel for
communicating with the pump module when the cuvette is operatively
coupled to the clot detection instrument; b) a sampling channel
communicating with the blood sample receptor-inlet and the at least
one test channel, at least the sampling channel having at least one
surface portion, a coating, an insert or liner, and any combination
thereof, that is hydrophilic; and c) a waste channel communicating
with the sampling channel; and iii) a vent opening communicating
with the sampling channel, wherein compressed air within the blood
clot detection instrument and the at least one test channel, the
sampling channel, the vent opening and waste channel, coact to
automatically draw a requisite volume of a blood sample deposited
at the blood receptor-inlet, into the sampling channel, and wherein
the at least one test channel of the cuvette, and the pump module
and the at least one pressure sensor of the clot detection
instrument, coact to perform a blood clotting time measurement on
the requisite volume of the blood sample.
22. The apparatus of claim 21, wherein the coaction between the
sampling channel and the vent opening includes a force generated by
the at least one surface portion of the sampling channel that is
hydrophilic and which draws the blood from the blood sample
deposited at the blood sample receptor-inlet into the sampling
channel and venting of air through the vent opening which is
displaced from the sampling channel by the incoming blood.
23. The apparatus of claim 21, wherein the channel arrangement
further comprises a vent channel connecting the vent opening with
the sampling channel.
24. The apparatus of claim 21, wherein the channel arrangement
further comprises a member associated with the waste channel for
delaying the filling of the waste channel until the sampling
channel is filled.
25. The apparatus of claim 21, wherein the channel arrangement is
formed in a surface of the main body.
26. The apparatus of claim 25, further comprising a substrate for
closing and sealing at least a portion of the channel arrangement
formed in the surface of the main body.
27. The apparatus of claim 26, wherein the substrate forms the at
least one surface portion of the sampling channel that is
hydrophilic.
28. The apparatus of claim 26, wherein the substrate comprises a
film with a hydrophilic surface, the hydrophilic surface of the
substrate forming the at least one surface portion of the sampling
channel that is hydrophilic.
29. The apparatus of claim 26, wherein the substrate comprises a
film and a layer of hydrophilic material disposed on the film, the
hydrophilic material forming the at least one surface portion of
the sampling channel that is hydrophilic.
30. The apparatus of claim 29, wherein the hydrophilic material is
an adhesive which attaches the substrate to the main body.
31. The apparatus of claim 21, further comprising a blood clotting
reagent disposed in the at least one test channel.
32. The apparatus of claim 21, wherein the at least one test
channel includes a section having at least one textured
surface.
33. The apparatus of claim 21, wherein the at least one test
channel includes a restriction.
34. The apparatus of claim 21, wherein the main body is made of one
of a hydrophobic material, a hydrophilic material, or a combination
of a hydrophobic material and a hydrophilic material.
35. The apparatus of claim 21, wherein the waste channel has at
least one surface portion, a coating, an insert or liner, and any
combination thereof, that is hydrophilic.
36. The apparatus of claim 21, wherein the at least one test
channel has at least one surface portion, a coating, an insert or
liner, and any combination thereof, that is hydrophilic or
hydrophobic.
37. The apparatus of claim 23, wherein the vent channel has at
least one surface portion, a coating, an insert or liner, and any
combination thereof, that is hydrophilic.
38. The apparatus of claim 24, wherein the member associated with
the waste channel comprises a jumper channel or a restriction.
39. The apparatus of claim 38, wherein the jumper channel or
restriction has at least one surface portion, a coating, an insert
or liner, and any combination thereof, that is hydrophilic.
40. The apparatus of claim 21, wherein the channel arrangement
further comprises a jumper channel connecting the waste channel
with the sampling channel, the jumper channel for delaying the
filling of the waste channel until the sampling channel is
filled.
41. A blood clot detection instrument for automatically measuring
blood clotting time of a blood sample contained in a test channel
of a cuvette, the blood clot detection instrument comprising: a
pump module for communicating with the test channel of the cuvette;
a pressure sensor; and a central processing unit executing
instructions for: operating the pump module in a pressure
alternating mode that causes a viscosity of the blood sample to
increase over time, the increase in viscosity of the blood causing
a pumping pressure of the pump module to increase over time;
obtaining a baseline pumping pressure from the pressure sensor upon
initial operation of the pump module in the pressure alternating
mode; obtaining additional pumping pressures over time from the
pressure sensor; determining a pumping pressure difference value
between each additional pumping pressure and the baseline pumping
pressure; comparing the pumping pressure difference value to a
predetermined threshold value; and indicating the blood clotting
time of the blood sample when the pumping pressure difference value
equals or exceeds the predetermined threshold value, the indicated
blood clotting time comprising a duration of time extending between
the measurement of the additional pumping pressure used for
determining the pumping pressure difference value that exceeded the
predetermined threshold value and the measurement of the baseline
pumping pressure.
42. The blood clot detection instrument of claim 41, wherein the
predetermined threshold may be fixed or dynamic.
43. The blood clot detection instrument of claim 41, wherein the
pump module, in the pressure alternating mode, creates positive and
negative pressures in the test channel of the cuvette.
44. The blood clot detection instrument of claim 41, wherein the
pump module, in the pressure alternating mode, reciprocally moves
the blood sample back and forth across a textured section or
restricted area of the test channel, thereby mixing the blood
sample with a reagent disposed in the test channel that triggers
and accelerates clotting of the blood sample.
45. The cuvette of claim 1, wherein the at least one test channel
comprises three test channels and further comprising a reagent in
each of the test channels.
46. The cuvette of claim 45, wherein the reagents are all the same,
different, or combinations thereof.
47. The apparatus of claim 21, wherein the at least one test
channel comprises three test channels and further comprising a
reagent in each of the test channels.
48. The apparatus of claim 47, wherein the reagents are all the
same, different, or combinations thereof.
49. The apparatus of claim 21, wherein air compressed within the
blood clot detection instrument, the at least one test channel of
the cuvette, and the section of the sampling channel extending
beyond the vent opening of the cuvette, coacts with the waste
channel to cause a leading edge of the blood sample drawn into the
sampling channel from the blood receptor-inlet, to pull back within
the sampling channel and uncover an optical sensor of the blood
clot detection instrument, the volume of the blood sample in the
sampling channel at the time when the blood sample is pulled back
to uncover the optical sensor, equaling the requisite volume, the
uncovering of the optical sensor activating the pump module of the
blood clot detection instrument, which draws the requisite volume
of the blood sample into the at least one test channel.
50. The cuvette of claim 1, further comprising: a first substrate
with hydrophilic properties for closing and sealing the sampling
channel and the waste channel; and a second substrate with
hydrophobic properties for closing and sealing the at least one
test channel.
51. The cuvette of claim 50, wherein the sampling channel and the
waste channel are formed in a first surface of the cuvette and the
first substrate is affixed to the first surface, and the at least
one test channel is formed in second surface of the cuvette and the
second substrate is affixed to the second surface.
52. The cuvette of claim 51, wherein the first and second surfaces
are opposed to one another.
53. The cuvette of claim 50, wherein the channel arrangement
further comprises: a vent channel connecting the vent opening with
sampling channel; and a jumper channel connecting the waste channel
to the sampling channel, for delaying the filling of the waste
channel until the sampling channel is filled, wherein the first
substrate closes and seals the vent channel and the jumper
channel.
54. The apparatus of claim 21, further comprising; a first
substrate with hydrophilic properties for closing and sealing the
sampling channel and the waste channel; and a second substrate with
hydrophobic properties for closing and sealing the at least one
test channel.
55. The apparatus of claim 54, wherein the sampling channel and the
waste channel are formed in a first surface of the cuvette and the
first substrate is affixed to the first surface, and the at least
one test channel is formed in second surface of the cuvette and the
second substrate is affixed to the second surface.
56. The apparatus of claim 55, wherein the first and second
surfaces are opposed to one another.
57. The apparatus of claim 54, wherein the channel arrangement
further comprises: a vent channel connecting the vent opening with
sampling channel; and a jumper channel connecting the waste channel
to the sampling channel, for delaying the filling of the waste
channel until the sampling channel is filled, wherein the first
substrate closes and seals the vent channel and the jumper channel.
Description
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Application No. 61/081,290, filed Jul. 16, 2008, the entire
disclosure of which is incorporated herein by reference.
FIELD
[0002] The invention relates to apparatus and methods for measuring
and testing blood coagulation. More particularly, the invention
relates to a cuvette-based apparatus for blood coagulation
measurement and testing having automatic volumetric blood sample
filling capability.
BACKGROUND
[0003] Many people take anticoagulants to maintain the theropedic
coagulation time of their blood. Depending upon the person, the
peak anticoagulant effect of the anticoagulant may be delayed by
many hours and/or days, and the duration of the effect may persist
after the peak for another four to five days. Accordingly, it is
critical that the people who take anticoagulants closely monitor
the coagulation time of their blood, so that they can monitor and
adjust the amount of the anticoagulant they are taking.
[0004] A common manner of determining the effective amount of
anticoagulant in a person's blood is to perform a prothrombin time
(PT) test. A PT test measures how long a sample of blood takes to
clot. As a result, the anticoagulation or hemostasis level in the
blood is directly proportional to the length of time required to
form clots.
[0005] Many devices and apparatus exist for performing coagulation
time measurements and tests. Some of these apparatus are portable
and simple enough to operate by a person in his or her home. An
example of such an apparatus is describe in U.S. Pat. No.
5,534,226, entitled PORTABLE TEST APPARATUS AND ASSOCIATED METHOD
OF PERFORMING A BLOOD COAGULATION TEST, issued to Gavin et al. and
assigned to International Technidyne Corporation, the assignee
herein. The apparatus described in this patent includes a
disposable cuvette and a testing device. In operation, a sample of
blood is placed into a cup-like supply reservoir of the cuvette,
the blood sample is drawn into the cuvette, and the coagulation
time of the blood sample is measured.
[0006] A problem associated with such apparatus, is that the volume
of the blood sample drawn into the cuvette for measurement and
testing is controlled by both the testing device and the sample cup
removal techniques. Moreover, the cup-like supply reservoir can be
messy to use.
[0007] Accordingly, a need exits for an improved apparatus for
measuring and testing blood coagulation.
SUMMARY
[0008] A cuvette is described herein for use with a blood clot
detection instrument. The cuvette comprises a blood sample
receptor-inlet and a channel arrangement comprising: at least one
test channel for performing a blood clotting time measurement; a
sampling channel communicating with the blood sample receptor-inlet
and the at least one test channel; a waste channel communicating
with the sampling channel; and a vent opening communicating with
the sampling channel. At least the sampling channel and the waste
channel each has at least one surface portion, a coating, an insert
or liner, and any combination thereof, that is hydrophilic. The
sampling channel with its at least one surface portion that is
hydrophilic, the vent opening and the waste channel with its at
least one surface portion that is hydrophilic, coact to
automatically draw a requisite volume of a blood sample deposited
at the blood receptor-inlet, into the sampling channel. More
specifically, air compressed within the blood clot detection
instrument, the at least one test channel of the cuvette, and the
section of the sampling channel extending beyond the vent opening
of the cuvette, coacts with the waste channel to cause the a
leading edge of the blood sample drawn into the sampling channel
from the blood receptor-inlet, to pull back within the sampling
channel and uncover an optical sensor of the blood clot detection
instrument. The volume of the blood sample in the sampling channel
at the time when the blood sample is pulled back to uncover the
optical sensor, equals the requisite volume. The uncovering of the
optical sensor activates a pump module of the blood clot detection
instrument, which draws the requisite volume of the blood sample
into the at least one test channel.
[0009] An apparatus is described herein for measuring blood
clotting time. The apparatus comprises: a blood clot detection
instrument and a cuvette for use with the blood clot detection
instrument. The blood clot detection instrument comprises: a pump
module and at least one pressure sensor. The cuvette comprises a
blood sample receptor-inlet; a channel arrangement comprising: at
least one test channel for performing a blood clotting time
measurement; a sampling channel communicating with the blood sample
receptor-inlet and the at least one test channel; and a waste
channel communicating with the sampling channel; and a vent opening
communicating with the sampling channel. At least the sampling
channel has at least one surface portion, a coating, an insert or
liner, and any combination thereof, that is hydrophilic. The
sampling channel with its at least one surface portion that is
hydrophilic, the vent opening and the waste channel coact to
automatically draw a requisite volume of a blood sample deposited
at the blood receptor-inlet, into the sampling channel, the
requisite volume of blood sample being drawn into the at least one
test channel when the pump module of the blood clot detection
instrument is activated. The at least one test channel of the
cuvette, and the pump module and the at least one pressure sensor
of the clot detection instrument, coact to perform a blood clotting
time measurement on the requisite volume of the blood sample.
[0010] Also described herein is a blood clot detection instrument
for automatically measuring blood clotting time of a blood sample
contained in a test channel of a cuvette. The blood clot detection
instrument comprises a pump module for communicating with the test
channel of the cuvette; a pressure sensor; and a central processing
unit. The central processing unit executes instructions for
operating the pump module in a pressure alternating mode that pumps
the blood sample back and forth in a test channel of a cuvette.
During clot formation, the viscosity of the blood sample increases
and causes a pumping pressure of the pump module to increase over
time. The central processing unit executes further instructions for
obtaining a baseline pumping pressure from the pressure sensor upon
initial operation of the pump module in the pressure alternating
mode; obtaining additional pumping pressures over time from the
pressure sensor; determining a pumping pressure difference value
between each additional pumping pressure and the baseline pumping
pressure; comparing each pumping pressure difference value to a
predetermined threshold value; and indicating the blood clotting
time of the blood sample when the pumping pressure difference value
exceeds the predetermined threshold value, the indicated blood
clotting time comprising a duration of time extending between the
measurement of the additional pumping pressure used for determining
the pumping pressure difference value that exceeded the
predetermined threshold value and the measurement of the baseline
pumping pressure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 is a schematic view of an embodiment of a
cuvette-based apparatus for measuring blood coagulation or clotting
time.
[0012] FIG. 2A is a schematic plan view of an embodiment of the
disposable cuvette.
[0013] FIG. 2B is a sectional view through line 2B-2B of FIG.
2A.
[0014] FIG. 2C is a sectional view through line 2C-2C of FIG.
2A.
[0015] FIG. 3A is an enlarged view of a blood sample testing
portion of the disposable cuvette shown in FIG. 2A.
[0016] FIG. 3B is a section view through line 3B-3B of FIG. 3A.
[0017] FIG. 4 is an enlarged view of a volumetric blood sampling
portion of the disposable cuvette shown in FIG. 2A.
[0018] FIG. 5 is a pressure profile and clot detection graph.
[0019] FIG. 6A is a schematic plan view of another embodiment of
the disposable cuvette.
[0020] FIG. 6B is a schematic plan view of a further embodiment of
the disposable cuvette.
[0021] FIG. 7A is a perspective view of a further embodiment of the
disposable cuvette.
[0022] FIG. 7B is an enlarged view of encircled area 7B in FIG.
7A.
[0023] FIG. 7C is a sectional view through line 7C-7C in FIG.
7B.
[0024] Like reference numbers and designations in the various
drawings indicate like elements.
DETAILED DESCRIPTION OF THE INVENTION
[0025] Referring to FIG. 1, there is shown a schematic view of an
embodiment of a cuvette-based apparatus 10 for measuring blood
coagulation or clotting time. The apparatus 10 generally comprises
a disposable cuvette 100 and a blood clot detection instrument 200.
The apparatus 10 may be used for measuring blood coagulation time
by depositing a sample of blood (whole blood or plasma) onto a
specified location of the disposable cuvette 100 and operatively
coupling the disposable cuvette 100 to the clot detection
instrument 200. The cuvette 100 automatically selects or fills
itself with a requisite volume of the blood sample (to be tested)
deposited at the specified location of the cuvette 100. The clot
detection instrument 200 facilitates automatic mixing of the blood
sample with a clotting reagent within the cuvette 100 and
automatically measures the clotting time of the selected volume of
the blood sample mixed with the clotting reagent within the
disposable cuvette 100, without contacting the blood sample. After
completion of the measurement, the cuvette 100 may be uncoupled or
removed from the clot detection instrument 200 and disposed of.
Because the clot detection instrument 200 does not contact the
blood sample, another cuvette 100 may be operatively coupled to the
clot detection instrument 200 for measuring another blood sample
without sterilization or other cleaning of the clot detection
instrument 200.
[0026] Referring still to FIG. 1, the clot detection instrument 200
comprises a pneumatic pump module 210, a motor 220 for driving the
pump module 210, a plurality of tubes 230 extending from the pump
module 210 for pneumatically coupling with the cuvette 100, a
pressure sensor 240 associated with each tube 230 for measuring the
pneumatic pressure within the tube 230, and an optical sensor 250
for optically sensing a sampling channel in the cuvette 100. In one
embodiment, the optical sensor 250 comprises, but is not limited,
to a LED/photo sensor. The clot detection instrument 200 also
comprises, without limitation, a central processing unit 260 (CPU)
executing instructions for controlling the operation of the motor
220 and thus the pump module 220 via signals received from the
optical sensor 250, and determining clotting time based on the
pressures sensed by the pressure sensors 240, a display (not shown)
for displaying the measured clotting time or other data related to
the measurement, a memory 270 for storing previously performed
measurements, and buttons, knobs, and/or switches (not shown) for
operating the clot detection instrument 200, controlling the
display and/or accessing stored data from the memory 270.
[0027] Referring now to FIGS. 2A-2C, there is collectively shown a
schematic plan view of an embodiment of the disposable cuvette 100.
The cuvette 100 comprises a substantially planar main body 110
defining generally planar top and bottom surfaces 111, 112. The
cuvette main body 110 is typically made from a rigid, transparent
hydrophobic or hydrophilic plastic material, using any suitable
forming method, such molding. The plastic hydrophobic materials may
include, without limitation polystyrene and polytetrafluoroethylene
and the plastic hydrophilic materials may include, without
limitation, styrene acrylonitrile, acrylonitrile styrene acrylate.
The cuvette main body 110 may also be made from other types of
rigid, transparent hydrophobic or hydrophilic materials. The
cuvette main body 110 includes an arrangement of open channels
formed in its bottom surface 112. The open channels are covered and
sealed by a thin, substrate 120 that is non-removably attached to
the bottom surface 112 of the cuvette body 110 When the cuvette
main body 110 is not made from a hydrophilic material or is made
from a hydrophobic material, the channels of the channel
arrangement each have at least one surface that is hydrophilic,
and/or has a hydrophilic coating, and/or has a hydrophilic insert
disposed therein (formed, for example, as a tube or liner, thereby
fully or partially lining the channel(s)), that facilitates the
automatic filling function of the cuvette 100.
[0028] In one embodiment, at least a top surface 121 of the thin
substrate 120, i.e., the surface in contact with the bottom surface
112 of the cuvette body 110, is hydrophilic or has hydrophilic
properties. The hydrophilic properties of the top surface 121 of
the substrate 120, facilitates the requisite volumetric selection
of the blood sample deposited on the cuvette 100, for coagulation
time measurement by the clot detection instrument 200. In other
embodiments, requisite volumetric selection of the blood sample is
accomplished by forming the cuvette body 110 from a hydrophilic
material.
[0029] The thin substrate 120, in one embodiment, is a transparent
film 122 coated on one side with a layer 122a of clear pressure
sensitive hydrophilic adhesive. The layer 122a of hydrophilic
adhesive forms the top surface 121 of the substrate 120 and
non-removably attaches the substrate 120 to the bottom surface 112
of the cuvette body 110. The transparent film 122 may comprise, in
one embodiment, a transparent polyester material.
[0030] In an alternative embodiment the transparent film 122 is
made from a hydrophilic material. Such a substrate may be attached
to the bottom surface 112 of the cuvette body 110 (with the top
surface 121 of the substrate 120 mated with the bottom surface 112
of the cuvette body 110) with a layer of adhesive applied to the
bottom surface 112 of cuvette body 110. Alternatively, such a
substrate may be attached to the bottom surface 112 of the cuvette
body 110 using heat sealing methods.
[0031] Referring still to FIGS. 2A-2C, the channel arrangement
formed in the bottom surface of the cuvette body 110 generally
comprises a sampling channel 130, one or more test channels 140 and
at least one waste channel 150. A first end 131 of the sampling
channel 130 communicates with a sample depositing area 160 formed
in a first or front end 113 of the cuvette body 110. The sample
depositing area 160 in the front end 113 of the cuvette body 110
and the exposed underlying portion of the substrate 120 form a
blood sample receptor and inlet 161 (receptor-inlet 161) on which
the entire blood sample is deposited. The sampling channel 130
extends longitudinally in the bottom surface of the cuvette body
110, from the receptor-inlet 161, and merges at its second end with
the one or more test channels 140 formed in the bottom surface of
the cuvette body 110.
[0032] The channel arrangement shown in FIGS. 2A-2C further
includes a jumper channel 170 that branches off from the sampling
channel 130 just downstream of the receptor-inlet 161 and fluidly
connects the waste channel 150 with the sampling channel 130. The
terminal end of the waste channel 150 communicates with a waste
channel venting aperture 151 formed transversely through the
cuvette body 110, which allows "dead" air displaced from within the
waste and jumper channels 150, 170 by incoming blood, to be vented
to the external environment. The waste channel venting aperture 151
is open to the external environment at the top surface 111 of the
cuvette body 110 and closed by the substrate 120 at the bottom
surface of the cuvette body 110.
[0033] The channel arrangement shown in FIGS. 2A-2C further
includes a vent channel 180 that branches off from the sampling
channel 130 downstream of the jumper channel 170. The vent channel
180 communicates with a vent opening 181 formed transversely
through the cuvette body 110 which allows "dead" air displaced from
within the sampling and vent channels 130, 180 by incoming blood to
be vented to the external environment. The vent opening 181 is open
to the external environment at the top surface 111 of the cuvette
body 110 and closed by the substrate 120 at the bottom surface of
the cuvette body 110.
[0034] As shown in FIG. 2C, the sampling channel 130 (and the
jumper, waste and vent channels 170, 150, 180) formed in the bottom
surface 112 of the cuvette main body 110 has a smooth top T surface
and smooth side surfaces S. The bottom surface B of the sampling
channel 130 (and the jumper, waste and vent channels 170, 150, 180)
is formed by the top surface 121 (e.g., hydrophilic adhesive layer
122a or the top surface of the hydrophilic film 122) of the
substrate 120, which is also smooth.
[0035] The cuvette main body 110, in some embodiments, is made from
a hydrophobic material. In such embodiments, the sampling, vent,
jumper, and waste channels 130, 180, 170, and 150, respectively,
each includes at least one surface that is hydrophilic, and/or has
a hydrophilic coating, and/or has a hydrophilic insert disposed
therein, that facilitates the automatic sample sizing function of
the cuvette 100.
[0036] In other embodiments, the cuvette main body 110 is made from
a hydrophilic material. The one or more test channels 140 in such
embodiments, each includes at least one surface that is
hydrophobic, and/or has a hydrophobic coating, and/or has a
hydrophobic insert disposed therein, where no automatic filling or
sample sizing function is required to be performed by the cuvette
100.
[0037] The requisite volume of blood sample selected by the cuvette
100 for measurement by the clot detection instrument 200, is
obtained from the blood sample deposited on the receptor-inlet 161.
The size of this volume is determined by the effective volume of
the sampling channel 130. The effective volume of the sampling
channel 130 is determined by the width of the sampling channel 130,
the height of the sampling channel 130, and length of the sampling
channel 130 as measured from point A, which is adjacent to the
receptor-inlet 161, to point B, which is adjacent to the vent
channel 180. The jumper channel 170, connecting the sampling
channel 130 to waste channel 150, delays the filling of the waste
channel 150 until the sampling channel 130 is completely filled.
The duration of the delay is controlled by an intersection I of the
jumper channel 170 and the waste channel 150 and the length and
cross-sectional area (CSA) of jumper channel 170 relative to the
CSA of the waste channel 150, which insure that blood from the
blood sample deposited on the receptor-inlet 161, is drawn into the
sampling channel 130 prior to being drawn into the waste channel
150. The delay time is determined by the cross section area and
length of the jumper channel 170. The duration of the delay may be
increased by lengthening the jumper channel 170, and/or decreasing
the cross-sectional area (width and height) of the jumper channel
170 relative to the CSA of the waste channel to increase flow
resistant through the jumper channel 170. Thus, during automatic
blood sample volume sizing, the intersection I of the jumper
channel 170 and the waste channel 150 acts like a resistor. Once a
blood sample is applied or deposited in the cuvette's
receptor-inlet 161, the blood sample enters the sampling channel
130 and the jumper channel 170 substantially simultaneously. While
the blood sample moves forward in the sampling channel 130, it also
fills the jumper channel 170, then stops at the intersection I of
the jumper channel 170 and the waste channel 150. The sampling
channel 130 continues to fill until an equilibrium state is
reached. The remaining sample in the receptor-inlet 161 then forces
the blood sample into the waste channel 150 from the jumper channel
170. The hydrophilic force of the waste channel 150 picks up and
draws off the remaining blood sample in the receptor-inlet 161.
[0038] In one embodiment where the cuvette comprises three test
channels 140, the sampling channel 130 has a width of about 0.055
inches, a height of about 0.014 inches, and a length of about 0.9
inches; the vent channel 180 has a width of about 0.010 inches, a
height of about 0.012 inches, and a length of about 0.140 inches;
the jumper channel 170 has a width of about 0.010 inches, a height
of about 0.012 inches, and a length of about 0.25 inches; and and
the waste channel 150 has a width of about 0.066 inches, a height
of about 0.014 inches, and length of about 2.24 inches. The three
test channels 140 of such a cuvette each has a width of about 0.030
inches and a height of about 0.010 inches. The length of each of
the outer two test channels is about 1.69 inches and the inner test
channel is about 1.634 inches. The sampling, jumper, waste, and
test channel(s) in other embodiments of the cuvette may have other
suitable dimensions.
[0039] FIG. 6A shows an another embodiment of the cuvette, denoted
by reference number 300. The cuvette 300 is substantially identical
to the cuvette 100 shown in FIG. 2A, except that the vent channel
extending between the sampling channel and the vent opening is
replaced by a vent opening 381 that directly opens into the
sampling channel 130.
[0040] FIG. 6B shows a further embodiment of the cuvette, denoted
by reference number 400. The cuvette 400 is substantially identical
to the cuvette 100 shown in FIG. 2A, except that the waste channel
450 communicates directly with the sampling channel 130 thereby
omitting the jumper channel. In addition, the waste channel 450
includes one or more restrictions 452 located just after the
entrance to the waste channel 450 that function to delay filing of
the waste channel 450.
[0041] FIGS. 7A-7C collectively show a further embodiment of a
cuvette, denoted by reference number 500. The cuvette 500 is
substantially identical to the cuvette 100 shown in FIG. 2A, except
that the one or more open test channels 140 are formed in the top
surface 111 of the main body 110 instead of in the bottom surface
112 of the main body 110 where the open sampling, vent, jumper, and
waste channels 130, 180, 170, 150 are formed. In addition, the open
one or more test channels 140 in the top surface 111 of the cuvette
main body 110 are covered and sealed by a thin substrate 530 with
hydrophobic properties (e.g., the substrate 530 includes a
hydrophobic adhesive coating or is a hydrophobic film) that is
non-removably attached to the top surface 111 of the cuvette main
body 110, and the open sampling, vent, jumper, and waste channels
130, 180, 170, 150 in the bottom surface 112 of the cuvette main
body 110 are covered and sealed by a thin, substrate 520 with
hydrophilic properties (e.g., the substrate 520 includes a
hydrophilic adhesive coating or is a hydrophilic film) that is
non-removably attached to the bottom surface 112 of the cuvette
body 110. As can be seen in FIGS. 7B and 7C, the sampling channel
103 and an inlet 540 to the one or more test channels 140 are
laterally offset from one another. A connecting channel 550 formed
in the top surface 111 of the cuvette main body 110, has a first
end 550a that communicates with a terminal end of the sampling
channel 103 and a second end 550b that communicates with an inlet
540 to the one or more test channels 140. The first end 550a of the
connecting channel 550 is covered and sealed by the hydrophillic
substrate 520. The remainder of the connecting channel 550
including the second end 550b thereof, is covered and sealed by the
hydrophobic substrate 530. The connecting channel 550 transfers the
volume of the blood sample precisely collected by the sampling
channel 130, to the one or more test channels 140.
[0042] In one embodiment, the one or more test channels 140
comprises a branched array of three test channels 140 in a
menorah-shaped configuration 140.sub.m (visible in FIGS. 2A, 3A, 4,
6A and 6B). The menorah-shaped array of test channels 140.sub.m
evenly divides the selected volume of blood into three separate
blood samples, thereby allowing the cuvette 100 to be used for
performing up to three different blood tests. For examples of the
blood tests that may be performed in the cuvette, see U.S. Pat. No.
5,534,226, entitled, PORTABLE TEST APPARATUS AND ASSOCIATED METHOD
OF PERFORMING A BLOOD COAGULATION TEST, assigned to the
International Technidyne Corporation, the assignee herein. The
entire disclosure of U.S. Pat. No. 5,534,226 is incorporated herein
by reference. The branched array in other embodiments of the
cuvette 100 may include two test channels 140 or more than three
test channels 140.
[0043] Referring still to FIGS. 2A, 3A, 4, 6A and 6B, the terminal
or marginal terminal end of each test channel 140 communicates with
a drive aperture 141 formed through the cuvette body 110. The drive
aperture 141 is open to the external environment at the top surface
112 of the cuvette body 110 and closed by the substrate 120 at the
bottom surface of the cuvette body 110. When the cuvette 100 is
operatively coupled to the clot detection instrument 200, as shown
in FIG. 1, the plurality of tubes 230 extending from the pump
module 210 sealingly engage the one or more drive apertures 141 of
the cuvette body 110, so that the arrangement of channels and the
pneumatic pump module 210 of the clot detection instrument 200 form
a pneumatic system when the cuvette 100 is operatively coupled to
the clot detection instrument 200.
[0044] Referring now to FIGS. 3A and 3B, each of the test channels
140 formed in the bottom surface of the cuvette body 110 includes
end sections 142a with smooth top, side and bottom walls (the
bottom wall of each test channel 140 being formed by the smooth top
surface 121 of the substrate 120) similar to the top, side and
bottom walls of the sampling, jumper and waste channels 130, 170,
and 150, and an intermediate section 142b where the top wall
T.sub.T and side walls S.sub.T are textured. In one non-limiting
embodiment, the texturing may comprise a flat knurl cross-hatch. In
other embodiments, the texturing in the intermediate section 142b
of one or more of test channels 140 may only be on the top wall or
on one or both of the side walls. The length of the textured
section is selected so that the blood sample BLD always remains
within this section of the test channel 140 during testing. A
dehydrated clot promoting reagent (not shown) for triggering and
accelerating blood clotting, is disposed in each test channel 140
where the texturing is located. The reagent in each test channel
140 may be the same or different. Therefore, in one embodiment,
reagent A may be in each of the test channels. In another
embodiment, reagent A may be in two of the test channels and
reagent B may be in one of the test channels. In still another
embodiment, reagent A may be in one of the test channels, reagent B
may be in one of the test channels and reagent C may be in one of
the test channels. When the blood sample is drawn into the test
channels 140, the reagent rehydrates and mixes with the blood. The
textured wall(s) of each test channel 140 improve reagent
deposition thereon during manufacture of the cuvette, and increase
clotting measurement sensitivity, as the blood sample is
reciprocally moved or oscillated therein when measuring of the
clotting time of the blood sample, as will be explained further on.
In an alternate embodiment, the textured intermediate section of
one or more the test channels 140 may be replaced by a restricted
area (not shown) where the test channel 140 is narrowed.
[0045] The automatic volumetric filling function of the cuvette 100
will now be described in greater detail with reference to FIG. 4.
Prior to volumetric filling, the cuvette 100 must be operatively
coupled to the clot detection instrument 200 such that the
plurality of tubes 230 extending from the pump module 210 of the
clot detection instrument 200 sealingly engage the one or more
drive apertures 141 of the cuvette body 110, thereby creating a
pneumatic system formed by the arrangement of channels of the
cuvette 100 and the pneumatic pump module 210 of the clot detection
instrument 200, as shown in FIG. 1. The automatic volumetric
filling function commences when a blood sample is deposited onto
the receptor-inlet 161 of the cuvette 100. The blood sample may be
deposited on the receptor-inlet 161 by finger after a fingerstick,
a needle, a dropper, a pipette, a capillary tube, or any other
suitable depositing device. Since at least a portion of the
sampling channel 130 is hydrophilic, a force F.sub.s is generated
by the hydrophilicity of this portion, which initially draws the
blood sample deposited on the receptor-inlet 161 into the sampling
channel 130 until the entire vent channel 180 becomes filled. The
dead air in the vent channel 180 and the section of the sampling
channel 130 extending between the receptor-inlet 161 and the vent
channel 180, is vented through the vent opening 181 of the vent
channel 180 as the blood BLD fills this section of the sampling
channel 130, and the vent channel 180. The blood drawn into the
vent channel 180 seals the vent opening 181. At the same time the
jumper channel hydrophilicity force F.sub.j draws blood into the
jumper channel. Once the vent channel 180 has been filled, the
force F.sub.s continues to draw more blood from the blood sample
deposited on the receptor-inlet 161 into the sampling channel 130
such that the blood BLD in the sampling channel 130 overshoots the
vent channel 180 and covers the optical sensor 250 of the clot
detection instrument 200, which lies under or over section or area
131 of the sampling channel 130. The blood BLD which overshoots the
vent channel 180 compresses the dead air volume contained within
the section of the sampling channel 130 extending beyond the vent
channel 180, the test channels 140, and the tubes 230 of the clot
detection instrument 200, and the pump module 210, because
F.sub.s>F.sub.p and F.sub.w<<F.sub.s, where F.sub.p is the
pressure of the compressed dead air volume, and F.sub.w is the
hydrophilicity force generated by at least a portion of the waste
channel 150 that is hydrophilic. Blood stops flowing in the
sampling channel 130 towards the test channels 140 when an
equilibrium state F.sub.s=F.sub.p+F.sub.w is achieved therein.
[0046] After the equilibrium state has been reached, blood that has
been delayed by the the jumper channel/waste channel intersection I
and the jumper channel 170, reaches the waste channel 150. The
waste channel 150 generates a force F.sub.w, that increases to a
value proportional to the line of contact between the blood and the
hydrophilic surface, which first pulls additional blood remaining
in the receptor-inlet 161 into the waste channel 150. As the waste
channel 150 fills with excess blood sample BLD, dead air disposed
therein and displaced by the incoming blood BLD is vented to the
external environment through the waste channel venting aperture
151. Once the remaining blood sample drawn off from the
receptor-inlet 161, force F.sub.w+F.sub.p becomes greater than
F.sub.s, and therefore, the leading edge E of the blood BLD in the
sampling channel 130 starts pulling back towards the vent channel
180.
[0047] The leading edge E of the blood BLD in the sampling channel
130 continues to be pulled back by force F.sub.w+F.sub.p and
uncovers the optical sensor 250. The volume of the blood sample BLD
disposed in the sampling channel 130 at the moment the optical
sensor 250 is uncovered, is the requisite volume. Consequently, the
pump module 210 of the clot detection instrument 200 is immediately
activated by the uncovered optical sensor 250 and draws this
requisite volume of blood sample BLD into the test channels 140
such that the blood sample BLD is disposed in the sections of the
test channels 140 that are textured. The ratio of force F.sub.w to
force F.sub.s determines the sample pull back speed. Generally, a
wider waste channel 150 has stronger pull back. In one,
non-limiting embodiment, the ratio of force F.sub.w to force
F.sub.s equals 1.2. One of ordinary skill in the art will recognize
that the forces described above may be adjusted by the material
properties of the cuvette body 110, substrate 120, size and/or
geometry of the plurality of channels. The blood sample over shoot
and pull back functions of the sampling channel 130 may also be
adjusted and controlled by the volume of dead air in the tubes 230
and pump module 210 of the clot detection instrument 200.
[0048] The automatic blood clot testing function of the cuvette 100
will now be described in greater detail with reference to FIGS. 3A
and 5. After the pump module 210 has drawn the blood sample into
one or more test channels 140 of the cuvette 100, the pump module
210 automatically switches into a pumping mode where it alternately
creates positive and negative pressures in the test channels 140 of
the cuvette 100. The alternating positive and negative pressures
(pumping pressure) reciprocally moves the blood samples BLD back
and forth across textured sections (or restricted areas) of the one
or more test channels 140, thereby mixing the blood sample with
dehydrated reagent, as shown in FIG. 3A. As the reagent rehydrates
and mixes with the blood sample BLD, it triggers and accelerates
the blood clotting cascade. Fibrin formation within the blood
sample BLD causes the viscosity of the blood sample BLD to increase
with time. The viscosity increase may be detected, in one
embodiment, by measuring the pumping pressure within each test
channel 140 over time. As shown in the graph of FIG. 5, the pumping
pressure starts at an initial pumping pressure value (pumping
pressure baseline .DELTA.P.sub.baseline) and increases with time,
as the viscosity of the blood increases during clotting. The
pressure sensors 240 of the blood clot detection instrument 200,
measure the pump pressure over time and the CPU 260 of the clot
detection instrument 200 compares this data to the initial pressure
baseline .DELTA.P.sub.baseline. The clotting time of the blood
sample may be determined when pressure value is greater than or
equal to a preset threshold. In one embodiment, the clotting time
is,
.DELTA.P.sub.end point-.DELTA.P.sub.baseline.gtoreq.threshold,
where .DELTA.P.sub.end point is the clotting end point peak to peak
pressure.
[0049] The preset threshold may be fixed or dynamic. In one
embodiment, a dynamic threshold may be,
.DELTA.P.sub.baseline+(0.3.times..DELTA.P.sub.baseline).
[0050] In general, the hydrophilicity of the one or more test
channels 140 will aid the robust automatic volumetric blood sample
filling function of the cuvette 100, while impeding the clotting
performance of the cuvette 100. Appropriately balancing the test
channel 140 dimensions, geometry, degree of texturing/restriction
size, and the hydrophilic properties of the cuvette body 110 and
substrate 120, will provide the cuvette 100 with requisite blood
clotting performance.
[0051] The pump profile of the pump module 210, i.e., pumping speed
and stroke, may also affect clotting performance. For example, a
pump speed greater than 20 millisecond (ms) per pump step,
equivalent to 20 ul per sec in test channel or a pump stroke
greater than 55 steps, equivalent to 0.044, may increase the chance
of deforming a weak clot (International Normalized Ratio>4.0),
which may in turn, result in lower clot detection precision. In one
embodiment, the pump profile is 40 ms per pump step and 36 steps
per pump direction (generates positive and negative pressures).
[0052] While exemplary drawings and specific embodiments have been
described and illustrated, it is to be understood that that the
scope of the present invention is not to be limited to the
particular embodiments discussed. Thus, the embodiments shall be
regarded as illustrative rather than restrictive, and it should be
understood that variations may be made in those embodiments by
workers skilled in the art without departing from the scope of the
present invention as set forth in the claims that follow and their
structural and functional equivalents.
* * * * *