Microfluidic device for single cell processing and method and system for single cell biophysical phenotyping using the microfluidic device

A method of manufacturing a microfluidic device for single cell processing, the method comprising:

• providing a substrate;
• forming a plurality of electrode channels, comprising a first electrode channel, a second electrode channel, a third electrode channel and a fourth electrode channel, in the substrate, each of the plurality of electrode channels containing an electrode material to form an electrode;
• and
• forming a plurality of fluidic channels, comprising a first fluidic channel and a second fluidic channel, in the substrate, each of the plurality of fluidic channels being configured to form a fluid pathway for allowing a fluid sample to flow through and at least one of the first and second fluidic channels comprising a cell manipulation portion, the cell manipulation portion comprising a plurality of constriction portions, wherein
• the first and second electrode channels are each coupled to the first fluidic channel and the electrodes of the first and second electrode channels are configured to measure an electrical impedance therebetween via the first fluidic channel, and
• the third and fourth electrode channels are each coupled to the second fluidic channel and the electrodes of the third and fourth electrode channels are configured to measure an electrical impedance therebetween via the second fluidic channel.

A system for single cell biophysical phenotyping, the system comprising:

• a microfluidic device for single cell processing, the microfluidic device comprising:
• a substrate;
• a plurality of electrode channels, comprising a first electrode channel, a second electrode channel, a third electrode channel and a fourth electrode channel, provided in the substrate, each of the plurality of electrode channels containing an electrode material to form an electrode;
• and
• a plurality of fluidic channels, comprising a first fluidic channel and a second fluidic channel, provided in the substrate, each of the plurality of fluidic channels being configured to form a fluid pathway for allowing a fluid sample to flow through and at least one of the first and second fluidic channels comprising a cell manipulation portion, the cell manipulation portion comprising a plurality of constriction portions, wherein
• the first and second electrode channels are each coupled to the first fluidic channel and the electrodes of the first and second electrode channels are configured to measure an electrical impedance therebetween via the first fluidic channel, and
• the third and fourth electrode channels are each coupled to the second fluidic channel and the electrodes of the third and fourth electrode channels are configured to measure an electrical impedance therebetween via the second fluidic channel;
• and
• a computing system comprising:
• a memory;
• and
• at least one processor communicatively coupled to the memory and the microfluidic device, and configured to:
• obtain a first impedance measurement based on the electrodes of the first and second electrode channels with the first fluidic channel having a fluid sample flowing therein;
• obtain a second impedance measurement based on the electrodes of the third and fourth electrode channels with the second fluidic channel having a fluid sample flowing therein;
• obtain a differential impedance measurement based on the first impedance measurement and the second impedance measurement, the differential impedance measurement comprising a differential impedance signal;
• and
• determine one or more biophysical properties of a single cell in the fluid sample that flowed in one of the first and second fluidic channels comprising the cell manipulation portion based on the differential impedance signal.