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基于集成光子学的片上流式细胞仪用于检测人类白细胞。

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

机构信息

imec, Kapeldreef 75, 3001, Leuven, Belgium.

Sarcura GmbH, Plöcking 2, Klosterneuburg, Austria.

出版信息

Sci Rep. 2024 May 20;14(1):10921. doi: 10.1038/s41598-024-60708-0.

Abstract

Differentiation between leukocyte subtypes like monocytes and lymphocytes is essential for cell therapy and research applications. To guarantee the cost-effective delivery of functional cells in cell therapies, billions of cells must be processed in a limited time. Yet, the sorting rates of commercial cell sorters are not high enough to reach the required yield. Process parallelization by using multiple instruments increases variability and production cost. A compact solution with higher throughput can be provided by multichannel flow cytometers combining fluidics and optics on-chip. In this work, we present a micro-flow cytometer with monolithically integrated photonics and fluidics and demonstrate that both the illumination of cells, as well as the collection of scattered light, can be realized using photonic integrated circuits. Our device is the first with sufficient resolution for the discrimination of lymphocytes and monocytes. Innovations in microfabrication have enabled complete integration of miniaturized photonic components and fluidics in a CMOS-compatible wafer stack. In combination with external optics, the device is ready for the collection of fluorescence using the on-chip excitation.

摘要

区分白细胞亚型,如单核细胞和淋巴细胞,对于细胞治疗和研究应用至关重要。为了保证细胞治疗中功能性细胞的经济高效输送,必须在有限的时间内处理数十亿个细胞。然而,商业细胞分选器的分选率还不够高,无法达到所需的产量。通过使用多台仪器进行并行处理,可以增加变异性和生产成本。通过在片上集成流体学和光学的多通道流式细胞仪,可以提供一种具有更高通量的紧凑型解决方案。在这项工作中,我们展示了一种具有整体集成光子学和流体制备的微流控芯片,并且证明了细胞的照明以及散射光的收集都可以使用光子集成电路来实现。我们的设备是第一个具有足够分辨率用于区分淋巴细胞和单核细胞的设备。微加工方面的创新使得小型化的光子组件和流体制备能够完全集成在一个 CMOS 兼容的晶圆堆叠中。与外部光学元件结合,该设备可以使用片上激发来收集荧光。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cc6/11106258/bac607ce086c/41598_2024_60708_Fig1_HTML.jpg

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