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On-chip flow cytometer using integrated photonics paves the way<br />

for high-throughput cell analysis<br />

Scalable on-chip detection of<br />

human white blood cells<br />

Imec, a world-leading research and innovation hub in nanoelectronics<br />

and digital technologies, and Sarcura GmbH, an Austrian<br />

early-stage technology start-up, present their proof-of-concept<br />

on-chip flow cytometer using integrated photonics. Published on<br />

20th May <strong>2024</strong> in Scientific Reports, part of the Nature Publishing<br />

Group, this innovation offers a unique platform for the detection<br />

and discrimination of human leukocytes and marks a significant<br />

stride towards cost-effective, scalable, and highly parallelized cell<br />

analysis.<br />

Accurate identification of human cells is a<br />

key operation in modern medicine, pivotal<br />

for understanding disease mechanisms and<br />

advancing targeted and personalized treatments.<br />

With the advent of cell manufacturing,<br />

living cells can now be engineered to<br />

function as treatments, notably in groundbreaking<br />

therapies like CAR-T immune cell<br />

therapy for cancer. The ability to identify<br />

these therapeutic cells in complex cell products<br />

at high throughput is crucial, and often<br />

time sensitive.<br />

The method of choice today is flow cytometry,<br />

which enables characterization of<br />

cell populations based on the physical and<br />

chemical characteristics of individual cells<br />

as they flow past a laser. However, the current<br />

implementation include bulky instrumentation,<br />

complex and manual workflows<br />

(posing contamination risks), and high<br />

operational costs. These challenges hinder<br />

widespread availability and adoption of cell<br />

therapies in decentralized settings.<br />

To address these limitations, imec<br />

harnesses its expertise in CMOS<br />

technology, photonics, and fluidics to<br />

automate, miniaturize and parallelize flow<br />

cytometry. In a study published in Scientific<br />

Reports imec, together with Sarcura, unveils<br />

an on-chip flow cytometer using integrated<br />

photonics. Fabricated on imec’s 200mm<br />

CMOS pilot line, the opto-fluidic chip features<br />

a pioneering material stack facilitating<br />

both cell illumination and capturing of scattered<br />

light through waveguide optics, and<br />

precise cell delivery to the detection points<br />

using microfluidic channels.<br />

“Silicon photonics, as successfully demonstrated<br />

in this novel photonic chip, is<br />

the revolutionary and essential building<br />

block that merges single-cell detection capabilities<br />

with massive parallelization on<br />

a dramatically miniaturized footprint. This<br />

breakthrough opens new possibilities for<br />

addressing previously unsolved challenges<br />

in applications such as cell therapy manu-<br />

Figure 2: (Left) Schematic cross-section of the chip layer stack, indicating light coupling<br />

into the chip, cell illumination, and collection and detection of cell scattering signals.<br />

(Right) Experimental scatter plot of a full peripheral blood mononuclear sample<br />

measured with the on-chip flow cytometer.<br />

Figure 1: Picture of the on-chip flow cytometer.<br />

facturing,“ states Daniela Buchmayr, CEO<br />

and Co-founder of Sarcura.<br />

Niels Verellen, Scientific Director at<br />

imec, remarked, “We have demonstrated,<br />

for the first time, that a monolithically integrated<br />

biophotonic chip can be used to collect<br />

optical scattering signals that allow the<br />

discrimination of lymphocytes and monocytes<br />

from a patient’s blood sample, rivaling<br />

the performance of commercial cytometers.<br />

The main advantage lies in the potential for<br />

dense parallelization of multiple flow channels<br />

to boost the system throughput.” In a<br />

next phase, the compact, alignment-free<br />

design should enable billions of cells to be<br />

identified within a limited amount of time.<br />

Crucially, the chip architecture seamlessly<br />

integrates with imec’s previously<br />

developed bubble jet cell sorting module,<br />

compatible with wafer-scale fabrication.<br />

Furthermore, the photonic components and<br />

layout can be tailored to suit specific applications.<br />

This proof-of-concept therefore<br />

marks a substantial leap towards cost-effective,<br />

scalable, and highly parallelized cell<br />

sorting platforms.<br />

IMEC Belgium<br />

BL 3001 Leuven<br />

www.reinraum.de | www.cleanroom-online.com NEWSLETTER | Edition <strong>EN</strong> <strong>07</strong>-<strong>2024</strong><br />

page 20/28

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