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

Monolithically-integrated cytometer for measuring particle diameter in the extracellular vesicle size range using multi-angle scattering
Monolithically-integrated cytometer for measuring particle diameter in the extracellular vesicle size range using multi-angle scattering
Size measurement of extracellular vesicles is hampered by the high cost and measurement uncertainty of conventional flow cytometers which is mainly due to the use of non-specialised free space optics. Integrated cytometry, where the optics and fluidics are embedded in a monolithic chip shows promise for the production of low cost, micro-flow cytometers dedicated for extracellular vesicle (EV) analysis with improved size measurement accuracy and precision. This research demonstrates a unique integrated cytometer for sub-micron particle size measurement using multi-angle scattering analysis. A combination of three technologies is used: (i) Dean-based hydrodynamic focussing to deliver a tight sample core stream to the analysis region, (ii) integrated waveguides with multimode interference devices to focus a narrow excitation beam onto the sample stream, and (iii) an angular array of collection waveguides to measure particle scattering distribution and calculate diameter. Low index 200 nm liposomes could be detected and polystyrene size standards as small as 400 nm diameter could be measured with an uncertainty of ± 21 nm (1/2 IQR) demonstrating a first step on the path to high performance integrated cytometry of EVs.
1473-0197
1267-1280
Butement, Jonathan
581ce321-f1af-4a2f-870a-9d8d45133586
Holloway, Paul
59a865d9-08bc-43c7-aa00-d80509956d86
Welsh, Joshua A
3bbcb204-ddcb-49c9-8cd4-f5e2906a666e
Holloway, Judith
f22f45f3-6fc8-4a4c-bc6c-24add507037c
Englyst, Nicola
f84399af-7265-4224-b556-102c3aa272b0
Horak, Peter
520489b5-ccc7-4d29-bb30-c1e36436ea03
West, Jonathan
f1c2e060-16c3-44c0-af70-242a1c58b968
Wilkinson, James S
73483cf3-d9f2-4688-9b09-1c84257884ca
Butement, Jonathan
581ce321-f1af-4a2f-870a-9d8d45133586
Holloway, Paul
59a865d9-08bc-43c7-aa00-d80509956d86
Welsh, Joshua A
3bbcb204-ddcb-49c9-8cd4-f5e2906a666e
Holloway, Judith
f22f45f3-6fc8-4a4c-bc6c-24add507037c
Englyst, Nicola
f84399af-7265-4224-b556-102c3aa272b0
Horak, Peter
520489b5-ccc7-4d29-bb30-c1e36436ea03
West, Jonathan
f1c2e060-16c3-44c0-af70-242a1c58b968
Wilkinson, James S
73483cf3-d9f2-4688-9b09-1c84257884ca

Butement, Jonathan, Holloway, Paul, Welsh, Joshua A, Holloway, Judith, Englyst, Nicola, Horak, Peter, West, Jonathan and Wilkinson, James S (2020) Monolithically-integrated cytometer for measuring particle diameter in the extracellular vesicle size range using multi-angle scattering. Lab on a Chip, 20 (7), 1267-1280. (doi:10.1039/C9LC01182J).

Record type: Article

Abstract

Size measurement of extracellular vesicles is hampered by the high cost and measurement uncertainty of conventional flow cytometers which is mainly due to the use of non-specialised free space optics. Integrated cytometry, where the optics and fluidics are embedded in a monolithic chip shows promise for the production of low cost, micro-flow cytometers dedicated for extracellular vesicle (EV) analysis with improved size measurement accuracy and precision. This research demonstrates a unique integrated cytometer for sub-micron particle size measurement using multi-angle scattering analysis. A combination of three technologies is used: (i) Dean-based hydrodynamic focussing to deliver a tight sample core stream to the analysis region, (ii) integrated waveguides with multimode interference devices to focus a narrow excitation beam onto the sample stream, and (iii) an angular array of collection waveguides to measure particle scattering distribution and calculate diameter. Low index 200 nm liposomes could be detected and polystyrene size standards as small as 400 nm diameter could be measured with an uncertainty of ± 21 nm (1/2 IQR) demonstrating a first step on the path to high performance integrated cytometry of EVs.

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Jbutemement_LOAC_2020_accepted_manuscript - Accepted Manuscript
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Accepted/In Press date: 28 February 2020
e-pub ahead of print date: 2 March 2020
Published date: 7 April 2020

Identifiers

Local EPrints ID: 438712
URI: http://eprints.soton.ac.uk/id/eprint/438712
ISSN: 1473-0197
PURE UUID: 36ca9040-4dd6-4b76-82c2-008b1de49a84
ORCID for Joshua A Welsh: ORCID iD orcid.org/0000-0002-1097-9756
ORCID for Judith Holloway: ORCID iD orcid.org/0000-0002-2268-3071
ORCID for Peter Horak: ORCID iD orcid.org/0000-0002-8710-8764
ORCID for Jonathan West: ORCID iD orcid.org/0000-0002-5709-6790
ORCID for James S Wilkinson: ORCID iD orcid.org/0000-0003-4712-1697

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Date deposited: 23 Mar 2020 17:30
Last modified: 23 May 2020 00:33

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Contributors

Author: Paul Holloway
Author: Joshua A Welsh ORCID iD
Author: Judith Holloway ORCID iD
Author: Nicola Englyst
Author: Peter Horak ORCID iD
Author: Jonathan West ORCID iD

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