Publications

Manufacturing Challenges in Cell and Gene Therapy, Deterministic Cell Separation (TM) (DCS) Microfluidics, CAR T-Cell Manufacturing Process and more...

DCS technology enables a breakthrough in producing T cell therapies, recovering more total and naive T cells with greater purity. This approach ensures minimal manipulation, significantly streamlined workflows, reduced need for skilled technician time, while simultaneously improving cell recovery and purity of leukocytes for apheresis products.

Demonstration of 80% cell recovery and 87% platelet depletion from apheresis blood products processed with DLD technology. DLD T-cell preparations showed a high conversion to the T-central memory (Tcm) phenotype and expanded well in culture, resulting in 2-fold greater Tcm compared to Ficoll and direct magnetic approaches. DLD processing provides a path to develop a simple, closed, and automated system for addressing multiple processing steps, human error, contamination, and other technical challenges when manufacturing of therapeutic cells.

Presents the reduction-to-practice of DLD technology with a commercially produced, high precision plastic microfluidic chip-based device designed for automated and simultaneous washing and size-based separation of human leukocytes, without centrifugation or manual handling of blood samples. The developed protocol averaged 88% WBC recovery, >99% removal, and >99% removal of unbound antibody in ~18 min for 200mL samples.

Review of DLD technology as an improved sample preparation method for flow cytometry, and highlighting how DLD processing can remove both RBCs and excess antibody without the need for lysing agents or centrifugation while eluting the target cells in an appropriate volume for rapid flow cytometry-based analysis.

Demonstration of improved RBC removal and unbiased WBC recovery from human whole blood samples with minimal hands-on time and no adverse affects on cell viability when using reduced-to-practice DLD technology in plastic microchip format.

A polymer-based chip-to-chip approach to purify circulating tumor cells. Microfluidic methods using DLD technology provide a uniquely effective and gentle way of processing cells. An example, presented here, being the isolation of CTCs from 1 in a billion blood cells from Breast Cancer Patients.

Demonstration of optimized DLD (single array) processing for whole blood samples resulting in high yield of harvested PC3 cancer cells. Processing larger blood volumes within one hour is achievable with additional DLD arrays on a single chip.

Presents how a microfluidic DLD device can isolate CTCs from blood with capture efficiencies >85% and at flow rate up to 10 mL/min with no impact on cell viability, enabling the option for downstream cell culture and analysis.

Demonstration of how an optimized DLD array post geometry reduces clogging, lowers hydrostatic pressure requirements, and increases the range of size-based displacement characteristic.

Report on the development of a high-throughput and highly efficient microfluidic device for isolating rare nucleated red blood cells from maternal blood.

Demonstration of on-chip cell treatments, such as labeling and washing, and bacterial lysis and chromosomal extraction, using DLD processing.