Biomimetic microfluidic chip for ultrasensitive captureof antigen-specific T cells
Adoptive T cell therapy is a promising cancer treatment but faces challenges in selecting
antigen-specific T cells and isolating cells based on receptor avidity. Traditional methods,
such as Dynabeads, are static and often lead to non-specific enrichment, reducing
therapeutic efficacy. In contrast, we developed a dynamic microfluidic screening system
that achieves two major breakthroughs: enhanced specificity and avidity-based T cell
isolation.
The first breakthrough enhances specificity by utilizing intracellular hydrogelation
technology to preserve intact cell membranes and mimic the immunological synapse. This
ensures precise enrichment of high-affinity T cells. Additionally, the microfluidic system
applies shear stress to remove temporary bonds from non-cognate T cells, further
improving specificity.
The second breakthrough isolates T cells based on receptor avidity. By applying controlled
flow rates and shear stress, the system dynamically separates T cells with varying binding
strengths. This allows for the identification of subsets with optimal therapeutic potential
while addressing safety concerns such as autoimmunity and exhaustion.
Unlike static methods, this platform provides real-time selection and scalability. It improves
specificity and enables avidity-based selection, overcoming key limitations in current
protocols. This dynamic system offers significant advancement for adoptive T cell therapy,
particularly in solid tumors where infiltration and specificity remain challenging.