Temperature-mediated catch-and-release cell sorting

Many biological, medical and pharmaceutical research studies require a specific cell type. However, it is difficult and sometimes impossible to isolate one cell type using current in vitro cell culture methods because of low yields, non-specific binding of unwanted cell types, and decreases in sorted cells' viability. This technology consists of a portable microfluidic device that integrates cell capture, fluid flow, and temperature control to isolate one cell type with high specificity. It can be used in a variety of research applications and has potential as a diagnostic tool for diseases like cancer that are characterized by a specific cell type.

Cells captured by surface-immobilized aptamers and released upon a temperature increase

This technology utilizes nucleic-acid- or peptide-based aptamers that are bound to the surface of a microfluidic device and that will bind to a particular cell type with high specificity. A liquid suspension of cells can be passed through the device, which will only capture the cell type of interest, allowing other cell types to be washed out. Upon a temperature increase facilitated by a heater integrated into the device, up to 80% of the captured cells will be released within one minute with negligible effects on their viability. Minimizing the size of the device enables cost-efficiency and precise control of cell immobilization. Several devices could potentially be used in parallel to allow for rapid cell sorting of multiple different cell types or to carry out several diagnostic analyses with one sample.

This technology was demonstrated using the sgc8c DNA aptamer, which binds selectively to CCRF-CEM cells.

Lead Inventor:

Qiao Lin, Ph.D.

Applications:

• Isolation of a specific cell type in vitro
• Cell identification and characterization
• Research tool for identifying new pharmaceuticals
• Can potentially be used in combination with micropatterning techniques as a platform for studying cell response
• Diagnostic tool for the detection and identification of cells associated with diseases (e.g cancer cells).

Advantages:

• Single platform can test for multiple diagnostic analyses
• Portable point of care form factor
• Low-cost implementation
• Can be created using standard micropatterning techniques

Patent Information:

Patent Pending (US20140296095)

Tech Ventures Reference: IR M11-113

Related Publications:

• Nguyen TH, Pei R, Stojanovic M, Lin Q. "Demonstration and characterization of biomolecular enrichment on microfluidic aptamer-functionalized surfaces." Sensors and Actuators B: Chemical, Vol. 155, Issue 1, Jul. 2011, pp. 58-66.
• Nguyen TH, Pei R, Landry D, Stojanovic M, Lin Q. "Microfluidic Aptameric Affinity Sensing of Vasopressin for Clinical Diagnostic and Therapeutic Applications." Sensors and Actuators B: Chemical, Vol. 154, Issue 1, May 2011, pp. 59-66.
• Zhu J, Nguyen T, Pei R, Stojanovic M, Lin Q. "Specific capture and temperature-mediated release of cells in an aptamer-based microfluidic device." Lab Chip. 2012 Sep 21;12(18):3504-13.
• Zhu J, Shang J, Jia Y, Pei R, Stojanovic M, Lin Q. "Spatially selective release of aptamer-captured cells by temperature mediation." IET Nanobiotechnol. 2014 Mar;8(1):2-9.