Microfabricated device with micro-environment sensors for assaying coagulation in fluid samples
The present invention relates to sample analysis cartridges comprising micro-environment sensors and methods for assaying coagulation in a fluid sample applied to the micro-environment sensors, and in particular, to performing coagulation assays using micro-environment sensors in a point of care sample analysis cartridge. For example, the present invention may be directed to a sample analysis cartridge including an inlet chamber configured to receive a biological sample, and a conduit fluidically connected to the inlet chamber and configured to receive the biological sample from the inlet chamber. The conduit may include a micro-environment prothrombin time (PT) sensor, and a micro-environment activated partial thromboplastin time (aPTT) sensor.
1 . An integrated circuit chip comprising:
a micro-environment prothrombin time (PT) sensor;
a micro-environment activated partial thromboplastin time (aPTT) sensor or a micro-environment activated clotting time (ACT) sensor, wherein the micro-environment PT sensor is on a same vertical plane as the micro-environment aPTT sensor or the micro-environment ACT sensor;
wherein the micro-environment PT sensor comprises a PT sensor polymer layer and one or more reagents for a PT analysis and the micro-environment aPTT sensor or the micro-environment ACT sensor comprises an aPTT sensor polymer layer or an ACT sensor polymer layer and one or more reagents for an aPTT or an ACT analysis,
wherein the micro-environment PT sensor polymer layer and the one or more reagents for the PT analysis are covalently bound to each other;
a first temporary electrical connector connected via a wiring to the micro-environment PT sensor; and
a second temporary electrical connector connected via another wiring to the micro-environment aPTT sensor or the micro-environment ACT sensor.
2 . The integrated circuit chip of claim 1 , wherein the micro-environment PT sensor comprises at least one reagent for inducing extrinsic coagulation pathway.
3 . The integrated circuit chip of claim 1 , wherein the micro-environment aPTT sensor or the micro-environment ACT sensor comprises at least one reagent for inducing intrinsic coagulation pathway.
4 . The integrated circuit chip of claim 1 , wherein the micro-environment PT sensor is an amperometric PT sensor, wherein the micro-environment aPTT sensor is an amperometric aPTT sensor, wherein the micro-environment ACT sensor is an amperometric ACT sensor, and wherein the first temporary electrical connector is an amperometric connector, and the second temporary electrical connector is an amperometric connector.
5 . The integrated circuit chip of claim 1 , further comprising a counter-reference electrode.
6 . The integrated circuit chip of claim 5 , wherein the counter-reference electrode completes a circuit on the integrated circuit chip, and the circuit includes the micro-environment PT sensor and the micro-environment aPTT sensor or the micro-environment ACT sensor.
7 . The integrated circuit chip of claim 1 , further comprising at least two conductometric sensors.
8 . The integrated circuit chip of claim 1 , wherein the one or more reagents in the micro-environment PT sensor comprise a thrombin-cleavable peptide with a detectable moiety.
9 . The integrated circuit chip of claim 1 , wherein the one or more reagents in the micro-environment aPTT sensor or the micro-environment ACT sensor comprise a thrombin-cleavable peptide with a detectable moiety.
10 . The integrated circuit chip of claim 1 , comprising: the micro-environment PT sensor; and the micro-environment aPTT sensor.
11 . The integrated circuit chip of claim 1 , comprising: the micro-environment PT sensor; and the micro-environment ACT sensor.