On-chip detection of white cells points to cost-effective blood analysis

22 May 2024

Imec and Sarcura develop flow cytometer with integrated photonics.

Belgian research center imec and Austrian cell therapy specialist Sarcura have collaborated on the development of a chip-scale flow cytometer instrument using integrated photonics.

The device, described in Scientific Reports and combining fluidics with optics on-chip, is said to be the first such instrument with sufficient resolution for the discrimination of white cells in blood samples.

This capability will allow it to be employed for detection and analysis of human leukocytes and monocytes, and marks a significant stride towards cost-effective, scalable, and highly parallelized cell analysis, according to the developers.

Flow cytometry, in which cells tagged with fluorescent markers are illuminated while flowing along a channel narrow enough to force the cells into roughly single file, has become a valuable technique for cell sorting and analysis, but its performance is controlled by the sample flow speeds and the efficiency of the optics employed.

On-chip flow cytometers, where the microfluidic and optical aspects of the process are integrated, can boost the performance, although one hurdle has been the difficulty of incorporating integrated waveguides to collect the scattered light which match the performance of bulk optics components for the same task.

Imec and Sarcura, collaborators on cytometry since 2021, set out to create a fully functional device for on-chip flow cytometry with monolithically integrated waveguide optics and fluidics, specifically one capable of detecting the scattered light of white blood cells.

"Current flow cytometry implementation includes bulky instrumentation, complex and manual workflows, and high operational costs," commented imec. "These challenges hinder widespread availability and adoption of cell therapies in decentralized settings."

The project tackled this via recent advances in micro-electro-mechanical systems and microelectronics technologies, allowing the chip to be constructed by bonding three wafers: a bottom silicon wafer with the illumination photonics, a middle silicon wafer containing the fluidics, and a top quartz wafer with the collection photonics.

Dramatically miniaturized device tackles unsolved challenges

Fabricated on imec’s 200-millimeter CMOS pilot line, this architecture creates "a pioneering material stack facilitating both cell illumination and capturing of scattered light through waveguide optics, and precise cell delivery to the detection points using microfluidic channels," said the developers.

In trials, the chip was able to "robustly detect" the side- and forward-scattered light of white blood cells, with sufficient resolution for the discrimination of both monocytes and lymphocyte populations in a sample.

The layered design should facilitate dense parallelization of multiple flow channels to boost the system throughput, and imec envisages a compact alignment-free design ultimately enabling billions of cells to be identified within a short period of time. The photonic components and layout can also be tailored, allowing different versions of the device to be designed for specific applications.

"Silicon photonics, as successfully demonstrated in this novel photonic chip, is the revolutionary and essential building block that merges single-cell detection capabilities with massive parallelization on a dramatically miniaturized footprint," said Daniela Buchmayr, Sarcura co-founder and CEO.

"This breakthrough opens new possibilities for addressing previously unsolved challenges in applications such as cell therapy manufacturing."