U.S. patent application number 12/091953 was filed with the patent office on 2008-11-27 for system to measure blood coagulation related parameters.
Invention is credited to Nicolas Blanc, Lynda Metref, Frederic Neftel, Laurent-Dominique Piveteau, Veronique Vallet.
Application Number | 20080294029 12/091953 |
Document ID | / |
Family ID | 35735162 |
Filed Date | 2008-11-27 |
United States Patent
Application |
20080294029 |
Kind Code |
A1 |
Piveteau; Laurent-Dominique ;
et al. |
November 27, 2008 |
System to Measure Blood Coagulation Related Parameters
Abstract
System to measure blood coagulation related parameters
comprising one first channel (6) adapted to contain a blood sample;
said system containing, at least partially, an expandable material
which is able to increase its volume when activated by an exciting
source; said system furthermore comprising several excitable
regions distributed close to said first channel (6), in such a way
that, when one of said excitable region is activated, said
expandable material increases to such an extend that the channel
cross section is reduced to a location situated at or near to said
excitable region.
Inventors: |
Piveteau; Laurent-Dominique;
(Bussigny, CH) ; Vallet; Veronique; (Bussigny,
CH) ; Neftel; Frederic; (Lausanne, CH) ;
Metref; Lynda; (Bussigny, CH) ; Blanc; Nicolas;
(Morges, CH) |
Correspondence
Address: |
NIXON & VANDERHYE, PC
901 NORTH GLEBE ROAD, 11TH FLOOR
ARLINGTON
VA
22203
US
|
Family ID: |
35735162 |
Appl. No.: |
12/091953 |
Filed: |
November 24, 2006 |
PCT Filed: |
November 24, 2006 |
PCT NO: |
PCT/IB2006/054432 |
371 Date: |
April 29, 2008 |
Current U.S.
Class: |
600/369 |
Current CPC
Class: |
B01L 3/502738 20130101;
B01L 2300/0887 20130101; B01L 3/502746 20130101; F16K 99/0001
20130101; Y10T 137/2191 20150401; B01L 2300/0816 20130101; F16K
99/004 20130101; G01N 33/4905 20130101; B01L 2400/0655 20130101;
F16K 99/0026 20130101; B01L 3/50273 20130101; F16K 99/0061
20130101; B01L 2400/0481 20130101; F16K 2099/0084 20130101; G01N
27/3271 20130101; F04B 43/043 20130101; B01L 2300/0825 20130101;
F16K 2099/008 20130101; B01L 2400/0672 20130101; F16K 2099/0086
20130101; Y10T 137/2196 20150401; F16K 99/0036 20130101; B01L
2300/0861 20130101 |
Class at
Publication: |
600/369 |
International
Class: |
A61B 5/00 20060101
A61B005/00 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 25, 2005 |
EP |
05111343.9 |
Claims
1. System to measure blood coagulation related parameters
comprising one first channel adapted to contain a blood sample;
said system containing, at least partially, an expandable material
which is able to increase its volume when activated by an exciting
source; said system furthermore comprising several excitable
regions distributed close to said first channel, in such a way
that, when one of said excitable region is activated, said
expandable material increases to such an extend that the channel
cross section is reduced at a location situated at or near to said
excitable region.
2. System according to claim 1 furthermore comprising at least a
second channel, said second channel being parallel to and
communication at one of its end with said first channel.
3. System according to claim 1 wherein said material is adapted to
be activated by heat, light, pH variation or by a chemical,
electromagnetic or radioactive element as exciting factor.
4. System according to claim 1 wherein said material is a mixture
comprising Expancel.RTM..
5. System according to claim 1 in combination with an exciting
source, such as a laser, which is distinct from said system.
6. System according to claim 1 furthermore comprising an exciting
source such as an electrical resistance.
7. System according to claim 1 wherein said channel is defined by
two horizontal and two lateral walls.
8. System according to claim 7 wherein at least one of said
horizontal walls is made of said expandable material.
9. System according to claim 1 wherein said channel cross section
is adapted to be reduced along a vertical direction.
10. System according to claim 7 wherein both lateral walls are made
of said expandable material.
11. System according to claim 10 wherein said channel cross section
is adapted to be reduced along a horizontal direction.
12. System according to claim 1 wherein the said material is
expandable and is a mixture comprising PDMS or a biocompatible
material.
13. System according to claim 1 wherein said channel(s) comprise(s)
at least a region of narrowing.
14. System according to claim 1, said system having a multilayered
structure comprising successively a substrate layer, an expandable
layer, a rigid layer and a cover layer, said substrate layer
incorporating said exciting source and said channel(s) being
defined in said rigid layer.
15. System according to claim 14 wherein said substrate layer is
made of PCB, said expandable layer is made of PDMSXB et said rigid
layer is made of PDMS.
16. System according to claim 1 furthermore comprising sensing
means.
17. System according to claim 16 wherein said sensing means are
diodes, optical density or impedance measuring means.
18. System according to claim 16 wherein said sensing means are
adapted to locate where the blood stops.
19. System according to claim 16 wherein said sensing means are
adapted to detect blood displacement.
20. Assembly comprising a system as defined in claim 1 in
combination with at least one reservoir communicating with said
channel(s), said reservoir(s) being adapted to contain reactive
which are used in the coagulation tests.
21. Use of a system or an assembly as defined in claim 1 for
determining the coagulation time based on the distance made by the
liquid along the channel before being stopped, said liquid being
moved by a sequential activation of said exciting sources.
22. Use of a multi-channel system or an assembly as defined in
claim 1 wherein each channel is used for a test.
23. Use according claim 22 wherein all channels are used for
carrying out the same test.
24. Use of a system or an assembly as defined in claim 1
characterized by the use of a pushing fluid which is non miscible
with blood and located between blood and the region of the channel
being closed.
Description
FIELD OF INVENTION
[0001] The invention relates to portable devices and methods for
measuring coagulation time, such as for example prothrombin time or
activated partial thromboplastine time.
STATE OF THE ART
[0002] In case of atrial fibrillation, deep venous thrombosis,
pulmonary embolism or after replacement of cardiac valve, taking
medication is necessary to maintain normal blood fluidity. The most
commonly used drugs are heparin and warfarin. Heparin is
administrated subcutaneously or intravenously. Heparin activates a
plasmatic protein, the antithrombin III that is a natural inhibitor
of protease implicated in the coagulation cascade (factors VIIa,
XIa, IXa, Xa, IIa). The rate of inactivation of these proteases by
AT-III increases 1000-fold due to the binding of heparin. Warfarin
decrease blood coagulation by interfering with vitamin K metabolism
by inhibiting the effective synthesis of biologically active forms
of the Vitamin-K-dependent clotting factors II, VII, IX and X, as
well as the regulatory factors protein C, protein S and protein Z.
Warfarin has the advantage that it may be taken orally. However
dosing warfarin is complicated by the fact that it is known to
interact with many commonly used medications and other chemicals
that may be present in appreciable quantities in food. But with
both medications, dangerous side effects such as bleeding exist.
Therefore in order to optimize the therapeutic effect and minimize
risks for the patient, close monitoring of the degree of
anticoagulation is required by blood testing. Two coagulation test
measures are routinely used: the prothrombin time and the activated
partial thromboplastin time. Both tests measure clotting time to
evaluate a patient's baseline haemostatic state or to monitor the
response to anticoagulant therapy as well as the overall function
and status of the coagulant system. Prothrombin time is tested when
warfarin is used and activated partial thromboplastin time when
heparin is used. These tests are mainly done in hospital with
relatively large laboratory instrument of complex technology and
therefore must be done by qualified personnel. These types of tests
are expensive and can be done only once a month approximately.
Another possibility is to use point-of-care device. In this case
the patient can perform the test by himself. This allows a better
control over time as the test can be done daily. However, even if
it has been shown self-management improves the quality of oral
anticoagulation [1], this method is little used. This is mainly due
to the cost of the test strips and to the complexity of use of the
actual devices. Therefore new easy of use and inexpensive
point-of-care devices and methods for blood coagulation testing are
needed.
[0003] Methods for coagulation measurement using portable device
are described in the following patents [0004] U.S. Pat. No.
5,908,786: measurement of blood displacement using liquid crystal
and heat [0005] U.S. Pat. No. 6,673,622 BI: measurement of change
in impedance [0006] WO 2005/114140: measurement of blood
displacement using magnetic beads [0007] U.S. Pat. No. 5,302,348:
measurement of blood displacement speed. [0008] U.S. Pat. No.
4,964,728: measurement of blood turbidity by optical means [0009]
US 2005/0233466: measurement of blood viscosity using ferromagnetic
agitator
REFERENCE
[0009] [0010] [1] C. Heneghan, Self-monitoring of oral
anticoagulation: a systematic review and meta-analysis, Lancet
2006, 367:404-11
GENERAL DESCRIPTION OF THE INVENTION
[0011] The present invention simultaneously concerns an alternative
and an improvement with respect to state-of-the-art
coagulometers.
[0012] To this effect it relates to a system to measure blood
coagulation related parameters comprising one first channel adapted
to contain a blood sample, the system containing, at least
partially, an expandable material which is able to increase its
volume when activated by an exciting source, said system
furthermore comprising several excitable regions distributed close
to said first channel, in such a way that, when one of said
excitable region is activated, said expandable material increases
to such an extend that the channel cross section is reduced at a
location situated at or near to said excitable region.
[0013] Preferred embodiments of the system according to the
invention are defined in the dependent claims.
[0014] The invention furthermore relates to the use of a system to
measure blood coagulation related parameters as defined above.
Wherein the coagulation time is based on the distance made by the
liquid along the channel before being stopped, said liquid being
moved by a sequential activation of the exciting elements.
[0015] The inventive concept is based on the measurement of the
displacement of blood along a channel. The displacement is driven
by the closing of a channel located in a material that can change
its volume when activated by an exciting factor. The device
includes a permanent and a disposable part. The disposable part is
in contact with blood and contains the channel in which the blood
will move. The permanent part contains an electronic that will
trigger the activation of the material and measure the
displacement. It also contains a screen to read the result of the
test. In the rest of this document, expansible material will be
described as PDMSXB, i.e. Expancel beads dispersed into a PDMS
matrix, and activation mean as heat produced by the resistance of
an electric circuit. Naturally this description can apply to any
material having the property to change its volume when activated by
an exciting factor.
DETAILED DESCRIPTION OF THE INVENTION
[0016] The invention will be better understood below with an
example illustrated by the following figures:
[0017] FIG. 1 is an illustration of the entire device (permanent
+disposable part)
[0018] FIG. 2 is a side view of disposable part with the channel
molded in the PDMS layer
[0019] FIG. 3 is a side view of disposable part with the channel
molded in the PDMSXB layer
[0020] FIG. 4 is a top view of the disposable part FIG. 5 is a
detailed view of a resistance
[0021] FIG. 6 is an illustration of the functioning of the device
from a front view
[0022] FIG. 7 is an illustration of the functioning of the device
from a side view
[0023] FIG. 8 is an illustration of the functioning of the device
with a non miscible fluid pushing the blood, from a side view
[0024] The following numerical references are used in the figures
[0025] 1. PCB [0026] 2. PDMS layer [0027] 3. PDMSXB layer [0028] 4.
protective layer [0029] 5. coverlayer [0030] 6. channel [0031] 7.
inlet hole [0032] 8. outlet hole [0033] 9. resistance [0034] 10.
region of narrowing [0035] 11. permanent part [0036] 12. disposable
part [0037] 13. measurement window [0038] 14. screen for result
reading [0039] 15. blood [0040] 16. non miscible fluid
[0041] The disposable part 12 is formed by the superposition of the
following layers: a PCB layer 1, a PDMS layer 2, a PDMSXB layer 4,
a protective layer 4 and a cover layer 5. The resistances 9
producing heat to activate the material are printed on the PCBlayer
1. The channel network in which the blood is displaced is molded in
the POMS or in the PDMSXB layer. The protective layer is preferably
biocompatible with blood and/or ensure thermal isolation of the
blood against the heated material. The protective layer can consist
of the superposition of two layers, one ensuring thermal isolation
and the other biocompatibility. The protective layer covering the
PDMS and the one covering the PDMSXB are not necessarily the same.
The cover layer closes the channel but preferably contain an inlet
hole that connect the channel to the outside in order to let the
blood enter the device and an outlet hole The disposable part is
preferably adapted to the sensing mean incorporated to the
permanent part, for example, if optical mean is used, the
disposable is preferably transparent to the light used by, for
example, containing a window.
[0042] The channel network preferably has the following properties:
[0043] The channel network contains at least two identical channels
to be able to perform the coagulation test and a control test in
the same time (FIG. 4). [0044] Each small channel in the network is
able to contain chemical species necessary for the test to be
performed and allow them to be mixed with blood. [0045] Each small
channel in the network contains a narrowing allowing to stop the
blood entering the device and therefore to control the volume of
blood displaced in each channel (FIG. 4)
[0046] The channel network may also have the following properties:
[0047] Each small channel may contain several narrowing to stop the
blood. [0048] The chemical species necessary for the test to be
performed are contained in reservoirs linked to the channel
network
[0049] The resistance printed on the PCB preferably has the
following properties: [0050] Under each channel a first resistance
is placed upstream of the narrowing. The size of this resistance
determines the volume of blood that will be displaced in the
channel. [0051] Downstream of the narrowing, identical resistance
are placed in series along a channel and in parallel along the
different channels. [0052] Each resistance consists in a folded
line. The foldings are more and more distant along the resistance
to allow a progressive heating and therefore a progressive closing
of the channel (FIG. 5).
[0053] Description of the functioning: sample of blood is taken
from the patient, for example with a lancet. The sample is placed
on the cover hole and is aspired inside the device by capillary
forces or by a pumping mechanism (FIGS. 6.b & 7.a). The sample
of blood fills the different channel until their narrowing where it
is stopped due to change in fluidic resistance. At this stage, it
may be mixed with chemical reactive needed to perform the test. The
resistances placed upstream the narrowing are heated and this part
of the channels is progressively closed and a volume of blood
corresponding to the size of the resistance is push forward in the
channel (FIGS. 6.c & 7.b). This allows controlling the volume
of blood to be analyzed. The resistances are then heated one after
the other along a channel, with a controlled amount of time between
each successive heating (FIGS. 6.d-e & 7.c). The resistances
are heated simultaneously along the different channels, in order to
compare the coagulation time in the different channel, i.e. the
coagulation time of blood mixed with different chemical. As long as
blood has not coagulated, it may be push forward by the closing of
the channel, but once coagulated it stays in place and the channel
may not be closed (FIGS. 6.f & 7.d). Coagulation time is
calculated by determining, for example optically, where the clot
stays and at what time the corresponding resistance was heated.
[0054] In order to avoid direct contact of the blood with the
activated region, another fluid that is non miscible with blood may
be placed upstream of the blood in the channel. This other fluid is
therefore the one that is displaced by the closing of the channel,
and its displacement induces blood displacement (FIG. 8).
[0055] Of course the present invention is not limited to the
embodiments discussed above.
* * * * *