Automated oxygen-dependent blood function measurement systems and methods
View Patent ↗Micro-electrical impedance-based assay systems (μZASs) for real-time monitoring of cellular response to an environmental condition are disclosed herein. An example microfluidic device can include: a cell channel configured to receive a sample substance (e.g., a blood sample), at least one gas channel operatively coupled to the cell channel defining a controlled testing environment of the microfluidic device, and a plurality of microfluidic impedance sensors configured to obtain electrical impedance-based measurements with respect to the sample substance.
1 . A micro-electrical impedance-based assay system (μZAS) for real-time monitoring of cellular response to an environmental condition, the μZAS comprising:
at least one microfluidic device comprising:
a cell channel configured to receive a sample substance;
a gas channel network comprising a plurality of gas channels, the gas channel network being operatively coupled to the cell channel, wherein the gas channel network comprises at least one valve and at least one gas cartridge defining a controlled testing environment of the at least one microfluidic device; and
a plurality of microfluidic impedance sensors configured to obtain, via one or more detection electrodes, electrical impedance-based measurement values with respect to the sample substance, wherein the at least one microfluidic device is operatively coupled to a gravity driven flow module configured to generate a gravity-driven hydrostatic pressure difference to drive a flow of the sample substance through the at least one microfluidic device; and
a measurement instrument operatively coupled to the at least one microfluidic device that is configured to control a testing environment of the at least one microfluidic device.
2 . The μZAS of claim 1 , further comprising:
a controller operatively coupled to the measurement instrument that is configured to determine and output at least one measurement value in relation to the sample substance to provide quantitative assessment of a hematological condition or outcome.
3 . The μZAS of claim 2 , wherein the controller is configured to determine at least one of a sickling index and/or sickle cell rheology.
4 . The μZAS of claim 2 , wherein the controller is configured to detect a change in electrical impedance above a predetermined threshold that is indicative of an abnormal blood flow.
5 . The μZAS of claim 2 , wherein the controller is configured to detect a PaO 2 transition resulting from resistance to electric currents associated with a corresponding sickling event.
6 . The μZAS of claim 2 , further comprising:
a display device or monitor operatively coupled to the μZAS and the controller configured to output at least a portion of the electrical impedance-based measurement values.
7 . The μZAS of claim 1 , wherein at least one of the electrical impedance-based measurement values is used to evaluate treatment efficacy for sickle cell disease, determine a biophysical marker of diabetes, assess whether blood flow is normal under hypoxia, or to evaluate dosage-dependencies of blood flow on medications.
8 . The μZAS of claim 1 , wherein the measurement instrument is configured to measure a rate of blood flow through the at least one microfluidic device.
9 . The μZAS of claim 1 , wherein the at least one microfluidic device and the measurement instrument are operatively coupled to one another via a magnetic, force, or snap-fit connection.
10 . The μZAS of claim 1 , wherein the at least one microfluidic device further comprises at least one microstructure for measuring a flow condition or obstruction.
11 . The μZAS of claim 1 , wherein each the at least one-gas channel is configured to supply at least a first gaseous substance and a second gaseous substance.
12 . The μZAS of claim 1 , wherein the gas channel network comprises a single inlet and a single outlet.
13 . The μZAS of claim 1 , wherein the plurality of microfluidic impedance sensors is positioned within the gas channel network.
14 . The μZAS of claim 1 , wherein the gravity driven flow module comprises a rocker module configured to facilitate programmable gravity-driven flow.
15 . The μZAS of claim 1 , wherein the μZAS is configured for blood testing under a plurality of controlled O 2 conditions or PaO 2 conditions.
16 . The μZAS of claim 1 , wherein the at least one microfluidic device comprises at least one disposable chip.
17 . The μZAS of claim 1 , wherein the plurality of microfluidic impedance sensors comprises 16 microfluidic impedance sensors.
18 . A micro-electrical impedance-based assay system (μZAS) for real-time monitoring of cellular response to an environmental condition comprising a plurality of microfluidic devices, each microfluidic device comprising:
a cell channel configured to receive a sample substance;
a gas channel network comprising a plurality of gas channels, the gas channel network being operatively coupled to the cell channel, wherein the gas channel network comprises at least one valve and at least one gas cartridge defining a controlled testing environment of each of the plurality of microfluidic devices; and
a plurality of microfluidic impedance sensors configured to obtain electrical impedance-based measurements with respect to the sample substance, wherein:
each microfluidic device is operatively coupled to a gravity driven flow module configured to generate a gravity-driven hydrostatic pressure difference to drive a flow of the sample substance through each respective microfluidic device, and
the plurality of microfluidic devices is operatively coupled to a measurement instrument that is configured to control a testing environment of each microfluidic device.