Femtosecond laser microfabrication of a PMMA lab on a chip for high throughput size-based inertial sorting

Inertial microfluidic particles sorting represents a critical task in many areas of biology, biotechnology, and medicine, including the isolation from blood of rare target cell populations, like e.g. circulating tumor cells (CTCs) and circulating fetal cells (CFCs). Usually, cell sorter microfluidic devices are fabricated by PDMS soft lithography, which is the most widespread micromanufacturing platform enabling to cost-effectively produce Lab-on-a-Chip with resolution in the nanometer scale. However, this technology presents some drawbacks: (i) due to PDMS softness, especially for high-pressure flows, the microfluidic behavior may change along the devices, leading to ambiguous results; (ii) soft-lithography allows to pattern structures on just one side of the chip thus limiting the affordable geometries to enhance the throughput of target particles. In this work, we develop a PMMA continuous size-based inertial microfluidic sorter by femtosecond laser microfabrication (FLM). The device design includes contracting and expanding channels (microchambers) provided with siphoning outlets on the backside of the chip. Since FLM technology is in principle applicable to any type of polymer, we chose PMMA, which is a biocompatible and transparent thermoplastic polymer much stiffer than PDMS. FLM allows machining the microfluidic network on both sides of the chip, making it possible the parallelization of the sorting process. In addition, thanks to the FLM flexibility, we easily varied the chambers number and the collecting strategy (at different flow rates) in order to define a device layout maximizing the trapping efficiency and throughput.