Extremely High-Throughput Parallel Microfluidic Vortex-Actuated Cell Sorting

Abstract

We demonstrate extremely high-throughput microfluidic cell sorting by making a parallel version of the vortex-actuated cell sorter (VACS). The set-up includes a parallel microfluidic sorter chip and parallel cytometry instrumentation: optics, electronics and control software. The result is capable of sorting lymphocyte-sized particles at 16 times the rate of our single-stream VACS devices, and approximately 10 times the rate of commercial cell sorters for an equivalent procedure. We believe this opens the potential to scale cell sorting for applications requiring the processing of much greater cell numbers than currently possible with conventional cell sorting.

Cell Granularity Reflects Immune Cell Function and Enables Selection of Lymphocytes with Superior Attributes for Immunotherapy

“…Sorting 1 × 10 7 cells at a speed of 10 000 cells s −1 at a 50% positive rate would require ≈30–60 min, which is acceptable considering the entire workflow of cell manufacturing (several weeks). Even higher throughput cell sorters in the pipeline, such as those based on Vortex Actuated Cell Sorting (VACS, cell flow rate ≈2 × 10 5 s −1 ), [ 63 ] would further simplify and provide the impetus for using this approach for improving cell manufacturing for immunotherapy.…”

A Microfluidics Approach for Ovarian Cancer Immune Monitoring in an Outpatient Setting

“…As can be seen from Figure 2 c, hydrodynamic focusing scores better in the four properties we were looking for: implementation on a small footprint, easy to integrate, scalable to multiple channels, and independent to the size and nature of the cells in the sample ( Figure 2 c). Other concepts, such as inertial focusing, for example, also scored high on scalability, as shown by Zuhkov et al [ 34 ], but required more space and were dependent on the cell sizes available in the sample. Once the cells are focused into the main channel, using 2D hydrodynamic focusing, they pass a narrow interrogation point downstream.…”

“…The higher the concept scores on a property, the closer the diamond will extend to the maximum of the corresponding axis. Relative scores between the hydrodynamic, acoustic, inertial, and DEP concept were provided based on the results reported in the literature [ 22 , 23 , 24 , 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. ( d ) Schematic of the optical system.…”

On-chip flow cytometer using integrated photonics for the detection of human leukocytes

“…With the successful implementation of cell therapy in clinical practice, there is a need to increase the throughput and automation of cell analysis and isolation techniques 1 . To guarantee the delivery of functional cells, cell therapies rely on the controlled processing of billions of cells by trained specialists in a limited timespan to ensure qualitative, cost-effective, and timely delivery to the patient 2,3 .…”

“…Nonetheless, when applied for cell sorting, it is the sorting module that primarily dictates the throughput. Once the maximum sorting rate is achieved, the implementation of parallelization across multiple channels becomes essentially the most promising approach to further enhance throughput 1 . In this context, the adoption of on-chip flow cytometry OPEN 1 imec, Kapeldreef 75, 3001 Leuven, Belgium.…”