Isolation and analysis of rare cells from biological fluids using a reversible cell capture platform

As blood carries rich information about one’s health state, there has been a constant and strong research effort in developing novel technologies to isolate disease specific biomarkers and bioparticles from blood. A significant advance is in the recent demonstration of circulating cancer cell isolation from blood into a microdevice for early stage diagnosis and prognosis of cancer metastasis. However, these microdevices immobilize target cells, limiting conventional cell culture as well as downstream cellular, proteomic and genomic analyses. Thus, the goal of the current project is to develop microchips that allow reversible cell capture and release, and characterize the purity, yield and function of isolated cells.

 

Specifically, the microchip will contain a sacrificial magnetic bead monolayer deposited by a convective deposition process. Both mathematical modeling and experimentation will be carried out to investigate the magnetic bead deposition process and drag/liftoff of cell/microsphere aggregates. Following the monolayer creation, the magnetic bead-covered substrate will be incorporated into a microfluidic channel and functionalized with an antibody to recognize and immobilize target cells from a biological fluid. As this magnetic layer can be lifted from the substrate in the presence of a magnetic field, cells attached on top can be released to a suspended state with minimal damage. Released cells will be studied using conventional cell activity and function analysis to validate the performance of the microfluidic cell isolation platform. This project is expected to provide the participated students with a multi-disciplinary training in areas including hemodynamics, cell adhesion, flow cytometry, microfluidics, and microscopy.