US 2016/0258968 A1 · A MICROFLUIDIC DEVICE FOR REAL-TIME CLINICAL MONITORING AND QUANTITATIVE ASSESSMENT OF WHOLE BLOOD COAGULATION

Abstract

In accord with one aspect, a microfluidic coagulation assessment device defining a plurality of microchannels is provided, wherein a blood sample is driven through the microchannels at a substantially constant flow rate and a controller is configured to, in combination with a timer and a pressure sensing device, determine a first pressure value (or flow value) at an initiation of flow, a first time (Tpg) at which a second pressure value is about twice the determined first pressure value, and a second time (Tpf) at which a third pressure value is about (1+e) times the determined first pressure value and establish a subject coagulation model predictive of channel occlusion therefrom. In another aspect, the blood sample is driven through the microchannels at a substantially constant pressure and a controller is configured to, in combination with a timer and a flow sensing device make the determination based on flow rate.

Claims64

Dependent claims

A microfluidic coagulation device, comprising:

at least one substrate defining a plurality of microchannels;
a first port at a first end portion of the substrate, the first port connecting to first ends of the plurality of microchannels;
a second port at a second end portion of the substrate, the second port connecting to second ends of the plurality of microchannels;
a first sensing device configured to determine a pressure value in, or relating to, a pressure across the plurality of microchannels;
a timer;
and
a controller configured to determine, in combination with the first sensing device and the timer, a first pressure value at an initiation of flow, a first time at which a second pressure value is determined to be about twice the determined first pressure value, and a second time at which a third pressure value is about (1+e) times the determined first pressure value, and further configured to establish a subject coagulation model predictive of channel occlusion in accord with the relation
Δ


P

(
t
)
Δ


P

(
0
)
=
1
+

t
-
T
pg
T
pf
-
T
pg
wherein Tpf is the second time and Tpg is the first time, and
wherein a differential pressure or flow rate/shear applied across the first port drives a blood sample across the plurality of microchannels at a substantially constant flow rate.

35 more elements

A method of assessing at least some aspects of a subject's coagulation from a blood sample taken from the subject, the method comprising the acts of:

driving the blood sample from the subject at a substantially constant flow rate through a plurality of microchannels formed in a microfluidic device substrate;
measuring a pressure, or a variable correlated with pressure, in at least one of the plurality of microchannels while the blood sample is moved through the plurality of microchannels at the substantially constant flow rate;
determining a first pressure value at an initiation of flow;
determining a first time at which a second pressure value is determined to be about twice the determined first pressure value;
determining a second time at which a third pressure value is determined to be about (1+e) times the determined first pressure value;
establishing a coagulation model predictive of channel occlusion for the subject using the first time and the second time in the relation
Δ


P

(
t
)
Δ


P

(
0
)
=
1
+

t
-
T
pg
T
pf
-
T
pg
wherein Tpf is the second time and Tpg is the first time;
and
recording, on a physical storage medium, the established subject-specific coagulation model.

35 more elements

A method of assessing at least some aspects of a subject's coagulation from a blood sample from the subject, the method comprising the acts of:

driving a first portion of the blood sample for a subject at a substantially constant flow rate through a first plurality of microchannels formed in a first microfluidic device substrate;
measuring a pressure, or a variable correlated with pressure, in at least one of the first plurality of microchannels while the first portion of the blood sample is moved through the first plurality of microchannels at the substantially constant flow rate;
determining a first pressure value at an initiation of flow;
determining a first time at which a second pressure value is determined to be about twice the determined first pressure value;
determining a second time at which a third pressure value is determined to be about (1+e) times the determined first pressure value;
establishing a first subject-specific coagulation model predictive of channel occlusion using the first time and the second time in the relation
Δ


P

(
t
)
Δ


P

(
0
)
=
1
+

t
-
T
pg
T
pf
-
T
pg
wherein Tpf is the second time and Tpg is the first time;
recording, on a physical storage medium, the established first subject-specific coagulation model;
driving a second portion of the blood sample for the subject at a substantially constant pressure through a plurality of second microchannel formed in the first microfluidic device substrate or in a second microfluidic device substrate;
measuring a flow rate, or a variable correlated with flow rate, in at least one of the plurality of second microchannels while the second portion of the blood sample is moved through the plurality of second microchannels at the substantially constant pressure;
determining a first flow rate value at an initiation of flow;
determining a first time at which a second flow rate value is determined to be about twice the determined first flow rate value;
determining a second time at which a third flow rate value is determined to be about (1+e) times the determined first flow rate value;
establishing a second subject-specific coagulation model predictive of channel occlusion using the first time and the second time in the relation
Q

(
t
)
Q

(
0
)
=
1
1
+

t
-
T
qg
T
qf
-
T
qg
wherein Tqf is the second time and Tqg is the first time;
and
recording, on the physical storage medium, the established second subject-specific coagulation model.

67 more elements

A method of assessing an effect of a modifier on blood coagulation, the method comprising the acts of:

driving a first portion of a blood sample at a substantially constant flow rate through a first plurality of microchannels formed in a microfluidic device substrate;
measuring a pressure, or a variable correlated with pressure, in at least one of the first plurality of microchannels while the first portion of the blood sample is moved through the first plurality of microchannels at the substantially constant flow rate;
determining a first pressure value at an initiation of flow of the first portion of the blood sample;
determining a first time at which a second pressure value of the first portion of the blood sample is determined to be about twice the determined first pressure value of the first portion of the blood sample;
determining a second time at which a third pressure value of the first portion of the blood sample is determined to be about (1+e) times the determined first pressure value of the first portion of the blood sample;
establishing a coagulation model predictive of channel occlusion for the first portion of the blood sample using the first time and the second time, for the first portion of the blood sample, in the relation
Δ


P

(
t
)
Δ


P

(
0
)
=
1
+

t
-
T
pg
T
pf
-
T
pg
wherein Tpf is the second time and Tpg is the first time;
driving a second portion of the blood sample at a substantially constant flow rate through a second plurality of microchannels formed in the microfluidic device substrate or another microfluidic device substrate;
adding a modifier to one of the second portion of the blood sample or the second plurality of microchannels;
measuring a pressure, or a variable correlated with pressure, in at least one of the second plurality of microchannels while the second portion of the blood sample is moved through the second plurality of microchannels at the substantially constant flow rate;
determining a first pressure value at an initiation of flow of the second portion of the blood sample;
determining a first time at which a second pressure value of the second portion of the blood sample is determined to be about twice the determined first pressure value of the second portion of the blood sample;
determining a second time at which a third pressure value of the second portion of the blood sample is determined to be about (1+e) times the determined first pressure value of the second portion of the blood sample;
establishing a coagulation model predictive of channel occlusion for the second portion of the blood sample using the first time and the second time, for the second portion of the blood sample, in the relation
Δ


P

(
t
)
Δ


P

(
0
)
=
1
+

t
-
T
pg
T
pf
-
T
pg
wherein Tpf is the second time and Tpg is the first time;
and
comparing the coagulation model predictive of channel occlusion for the first portion of the blood sample to the coagulation model predictive of channel occlusion for the second portion of the blood sample to determine an effect of the modifier.

72 more elements

A method of assessing an effect of a modifier on blood coagulation, the method comprising the acts of:

driving a first portion of a blood sample at a substantially constant pressure through a first plurality of microchannels formed in a microfluidic device substrate;
measuring a flow rate, or a variable correlated with flow rate, in at least one of the first plurality of microchannels while the first portion of the blood sample is moved through the first plurality of microchannels at the substantially constant pressure;
determining a first flow rate value at an initiation of flow of the first portion of the blood sample;
determining a first time at which a second flow rate value of the first portion of the blood sample is determined to be about twice the determined first flow rate value;
determining a second time at which a third flow rate value of the first portion of the blood sample is determined to be about (1+e) times the determined first flow rate value;
establishing a first coagulation model predictive of channel occlusion for the first portion of the blood sample using the first time and the second time in the relation
Q

(
t
)
Q

(
0
)
=
1
1
+

t
-
T
qg
T
qf
-
T
qg
wherein Tqf is the second time and Tqg is the first time;
driving a second portion of the blood sample at the substantially constant pressure through a second plurality of microchannels formed in the microfluidic device substrate or another microfluidic device substrate;
adding a modifier to one of the second portion of the blood sample or the second plurality of microchannels;
measuring a flow rate, or a variable correlated with flow rate, in at least one of the second plurality of microchannels while the second portion of the blood sample is moved through the second plurality of microchannels at the substantially constant pressure;
determining a first flow rate value at an initiation of flow of the second portion of the blood sample;
determining a first time at which a second flow rate value of the second portion of the blood sample is determined to be about twice the determined first flow rate value of the second portion of the blood sample;
determining a second time at which a third flow rate value of the second portion of the blood sample is determined to be about (1+e) times the determined first flow rate value of the second portion of the blood sample;
establishing a second coagulation model predictive of channel occlusion for the second portion of the blood sample using the first time and the second time, for the second portion of the blood sample, in the relation
Q

(
t
)
Q

(
0
)
=
1
1
+

t
-
T
qg
T
qf
-
T
qg
wherein Tqf is the second time and Tqg is the first time;
and
comparing the coagulation model predictive of channel occlusion for the first portion of the blood sample to the coagulation model predictive of channel occlusion for the second portion of the blood sample to determine an effect of the modifier.

62 more elements

Dependencies are inferred from the claim text.

A microfluidic device for real-time clinical monitoring and quantitative assessment of whole blood coagulation

Life of this patent

A microfluidic device for real-time clinical monitoring and quantitative assessment of whole blood coagulation

Life of this patent

Abstract

Claims64