Method and system for single-cell biophysical profiling using a microfluidic device

An optics-free system for single-cell profiling, the system comprises:

• a microfluidic device comprising a sample flow channel extending through a particle focusing region and a detection region, wherein the detection region comprises a cell deformation zone, a first pair of electrodes and a second pair of electrodes, wherein the first and second pair of electrodes are respectively arranged before and after the cell deformation zone;
• and
• a computing system comprising:
• a memory;
• and at least one processor communicatively coupled to the memory and the first and second pair of electrodes of the microfluidic device,
• wherein the computing system is configured to:
• (i) measure an impedance response of each cell flowing past the first pair of electrodes disposed along the sample flow channel within the detection region;
• (ii) measure an impedance response of each cell after deformation flowing past the second pair of electrodes disposed along the sample flow channel within the detection region;
• and
• (iii) determine one or more quantitative relationships among impedance responses from one or a combination of the first and second pair of electrodes to quantify one or more biophysical properties of each cell for profiling of said cell.

The system of claim 23, wherein the computing device is configured to:

• (i) determine a ratio of the first impedance signal at the first frequency and the second impedance signal at the second frequency to quantify a membrane opacity of each cell as one of the one or more biophysical properties for said cell;
• and/or
• (ii) determine a ratio of the first impedance signal at the first frequency and the third impedance signal at the third frequency to quantify a nucleus opacity of each cell as one of the one or more biophysical properties for said cell;
• and/or
• (iii) quantify a cell size of each cell based on the first impedance signal at the first frequency of the first pair of electrodes.

A microfluidic device for single-cell profiling, comprising:

• a first flow channel to form a fluid pathway for allowing a fluid sample comprising cells to flow from a sample inlet to an outlet, wherein the first flow channel comprises a particle focusing region;
• a second flow channel to form a fluid pathway for allowing a sheath fluid to flow from a sheath fluid inlet to a junction, wherein the second flow channel intersects with the first flow channel to form the junction in a cell deformation zone;
• two pairs of electrodes arranged adjacent to the junction, wherein the at least two pairs of electrodes and the junction define a detection region,
• wherein the two pairs of electrodes comprise a first pair of electrodes and a second pair of electrodes, and
• wherein the first pair of electrodes extend across the first flow channel upstream of the junction, and wherein the second pair of electrodes extend across the first flow channel downstream of the junction.