Developing a low cost, highly compact holographic imaging based microfluidic cell sorting system using 3D printing

SUMMARY With advancement in machine vision and deep learning, imaging-based microfluidics have demonstrated their potential to serve as precise single cell analysis and sorting devices for various challenging medical applications including bioprinting and cell patterning, sorting rare cells (e.g., circulating tumor cells, sickle cells) from blood for disease (e.g., cancer, sickle diseases) diagnosis, etc. However, current imaging-based microfluidic cell sorting systems suffer from the issues of low throughput and world-to-chip interfacing. These issues are largely related to the shallow depth of field of conventional microscopic imaging, which significantly restricts the number of cells that can be analyzed per image and increases the complexity and cost involved in fabricating cell sorting chips integrated with imaging and valve actuation capabilities. These issues limit the implementation of such microfluidic systems in clinical diagnostics and treatment, particularly in which target cells are extremely rare in samples. Although different types of high throughput cell sorting microfluidic systems have been developed, they either have insufficient sorting precision or require the integration of different sorting methods, which further increases the system complexity and lowers its reliability. This exploratory R21 project aims to develop a high throughput, low cost and compact solution for imaging- based cell sorting microfluidic devices to improve their appeal for critical clinical applications. Our solution utilizes 3D holographic imaging to overcome the depth of field issue of conventional microscopic imaging, increase the specificity of cell detection, and enables high throughput and high precision cell sorting using microfluidics. We will use multi-material 3D printing technique to generate fast responsive sorting valves and miniaturized holographic imaging sensors with performance that exceeds the ones in the literature. Our approach will not only substantially reduce the cost, time, and enhance the degree of automation for fabricating these microfluidic devices, but also enable sleek and compact microfluidic design, contamination-free fabrication, and superior and consistent imaging quality during hours of operation that is essential for many clinical operations. The 3D printing approach developed in this project can provide the basis for low cost and high efficiency fabrication of a broad range of microfluidic devices used in medical research and clinical applications (e.g., lab-on-a-chip diagnostics, point-of-care systems, organ replication-on-a-chip, and bioassays). The integration of 3D imaging capability with 3D printing will enable new designs of high throughput, high precision, and high specificity microfluidic systems with versatile functionalities that are not available in conventional microfluidics used in medical field. In particular, the cell sorting devices fabricated in this proposed project can significantly speed up the cell-based liquid biopsy for cancer diagnostics and personalized cancer treatment.