Microfluidic device for real-time clinical monitoring and quantitative assessment of whole blood coagulation
First Claim
1. 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
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Accused Products
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.
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Citations
63 Claims
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1. A microfluidic coagulation device, comprising:
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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 - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
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17. A microfluidic coagulation device, comprising:
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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 flow rate in, or relating to, the plurality of microchannels, a timer; and a controller configured to determine, in combination with the first sensing device and the timer, (i) a first flow rate value at a first time corresponding to an initiation of flow, (ii) a second time at which a second flow rate value is determined to be about half the determined first flow rate value, (iii) a third time at which a third flow rate value is determined to be about (1+e) times lesser than the determined first flow rate value, and (iv) a blood coagulation model predictive of channel occlusion governed by the relation - View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
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33. 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:
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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 - View Dependent Claims (34, 35, 36, 37)
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38. 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:
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driving the blood sample at a substantially constant pressure through a 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 plurality of microchannels while the blood sample is moved through the plurality of 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 subject-specific coagulation model predictive of channel occlusion for the subject using the first time and the second time in the relation - View Dependent Claims (39, 40)
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41. 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:
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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
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42. 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:
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driving the blood sample 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 subject-specific coagulation model predictive of channel occlusion; and recording, on a physical storage medium, the subject-specific coagulation model, the subject-specific coagulation model utilizing the relation
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43. A method of assessing coagulation of a subject'"'"'s blood sample, the method comprising the acts of:
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driving the blood sample at a substantially constant pressure through a 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 plurality of microchannels while the blood sample is moved through the plurality of 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; recording, on a physical storage medium, a subject-specific coagulation model, the subject-specific coagulation model utilizing the relation
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44. A method of assessing an effect of a modifier on blood coagulation, the method comprising the acts of:
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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 - View Dependent Claims (45, 46, 47, 48, 49, 50, 51, 52, 53)
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54. A method of assessing an effect of a modifier on blood coagulation, the method comprising the acts of:
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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 - View Dependent Claims (55, 56, 57, 58, 59, 60, 61, 62, 63)
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Specification