Monolithically-integrated cytometer for measuring particle diameter in the extracellular vesicle size range using multi-angle scattering

Butement, Jonathan; Holloway, Paul M.; Welsh, Joshua; Holloway, Judith A.; Englyst, Nicola A.; Horák, Péter; West, Jonathan; Wilkinson, James S.

doi:10.1039/c9lc01182j

Cited by 5 publications

(4 citation statements)

References 34 publications

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“…However, this loss can be compensated by either the optimization of the downstream light path, preventing lossy dichroic mirrors, or by maximizing the incoupling of light into the optical fiber. Both advances have successfully led to high sensitivity in a new generation of conventional cytometers from Beckman Coulter [40]. The same concept could be explored on a chip by incorporating flat optics in the quartz top or in the silicon when the full light collection path is integrated and no optical access is required [41].…”

Section: Discussionmentioning

confidence: 99%

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

Libbrecht,

Vankerckhoven,

de Wijs

et al. 2023

Cells

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Among cancer diagnoses in women, ovarian cancer has the fifth-highest mortality rate. Current treatments are unsatisfactory, and new therapies are highly needed. Immunotherapies show great promise but have not reached their full potential in ovarian cancer patients. Implementation of an immune readout could offer better guidance and development of immunotherapies. However, immune profiling is often performed using a flow cytometer, which is bulky, complex, and expensive. This equipment is centralized and operated by highly trained personnel, making it cumbersome and time-consuming. We aim to develop a disposable microfluidic chip capable of performing an immune readout with the sensitivity needed to guide diagnostic decision making as close as possible to the patient. As a proof of concept of the fluidics module of this concept, acquisition of a limited immune panel based on CD45, CD8, programmed cell death protein 1 (PD1), and a live/dead marker was compared to a conventional flow cytometer (BD FACSymphony). Based on a dataset of peripheral blood mononuclear cells of 15 patients with ovarian cancer across different stages of treatment, we obtained a 99% correlation coefficient for the detection of CD8+PD1+ T cells relative to the total amount of CD45+ white blood cells. Upon further system development comprising further miniaturization of optics, this microfluidics chip could enable immune monitoring in an outpatient setting, facilitating rapid acquisition of data without the need for highly trained staff.

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Section: Discussionmentioning

confidence: 99%

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

Libbrecht,

Vankerckhoven,

de Wijs

et al. 2023

Cells

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“…The main drawback of these devices lies in the manual assembly, making them expensive for mass production. Integrated devices, with both microfluidics and photonics fully integrated on-chip, have been demonstrated as well, but their operation has been limited to the discrimination of microbeads or cell counting [15][16][17][18] . Nowadays, technology platforms for the fabrication of integrated photonics with high refractive index materials are becoming standard.…”

Section: On-chip Flow Cytometer Using Integrated Photonics For the De...mentioning

confidence: 99%

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

Jooken,

Zinoviev,

Yurtsever

et al. 2024

Sci Rep

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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.

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“…181 Large-scale arrays of waveguides and resonators can be readily fabricated on chip and could be useful in high-throughput detection of rare biological targets. 182,183 Evanescent interaction can also be used to excite fluorophores at specific locations for spatially multiplexed or high-throughput imaging analysis. This capability was demonstrated for on-chip super-resolution microscopy, in which fluorescent probes are excited by the evanescent field of a waveguide implemented using silicon nitride to operate in the visible range.…”

Section: Lensless On-chip Optics With Integrated Photonicsmentioning

confidence: 99%

The next generation of hybrid microfluidic/integrated circuit chips: recent and upcoming advances in high-speed, high-throughput, and multifunctional lab-on-IC systems

2023

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Monolithically-integrated cytometer for measuring particle diameter in the extracellular vesicle size range using multi-angle scattering

Abstract: On chip MMI-lenses combined with multi-angle waveguide collection and 3d focussing fluidics allows high performance size measurement of submicron particles.

Cited by 5 publications

References 34 publications

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

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

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

The next generation of hybrid microfluidic/integrated circuit chips: recent and upcoming advances in high-speed, high-throughput, and multifunctional lab-on-IC systems

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