TY - JOUR
T1 - Microfluidic Impedance-Deformability Cytometry for Label-Free Single Neutrophil Mechanophenotyping
AU - Petchakup, Chayakorn
AU - Yang, Haoning
AU - Gong, Lingyan
AU - He, Linwei
AU - Tay, Hui Min
AU - Dalan, Rinkoo
AU - Chung, Aram J.
AU - Li, King Ho Holden
AU - Hou, Han Wei
N1 - Funding Information:
This research was supported by Singapore Ministry of Education Academic Research Fund (MOE ACRF) Tier 1 (RG53/18), MOE AcRF Tier 2 (MOE‐T2EP30120‐0004), and A. Menarini Biomarkers Pte Ltd. C.P. acknowledged support for the NTU‐RSB Postdoctoral Fellowship. Authors acknowledged the supports from Prof. Dalton Chor Yong Tay and Dr. Jun Kit Wang for viscosity measurement and Prof. Siu Ling Wong for HL‐60 cell line and culturing procedures. Schematics were created with BioRender.com.
Funding Information:
This research was supported by Singapore Ministry of Education Academic Research Fund (MOE ACRF) Tier 1 (RG53/18), MOE AcRF Tier 2 (MOE-T2EP30120-0004), and A. Menarini Biomarkers Pte Ltd. C.P. acknowledged support for the NTU-RSB Postdoctoral Fellowship. Authors acknowledged the supports from Prof. Dalton Chor Yong Tay and Dr. Jun Kit Wang for viscosity measurement and Prof. Siu Ling Wong for HL-60 cell line and culturing procedures. Schematics were created with BioRender.com.
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/5/5
Y1 - 2022/5/5
N2 - The intrinsic biophysical states of neutrophils are associated with immune dysfunctions in diseases. While advanced image-based biophysical flow cytometers can probe cell deformability at high throughput, it is nontrivial to couple different sensing modalities (e.g., electrical) to measure other critical cell attributes including cell viability and membrane integrity. Herein, an “optics-free” impedance-deformability cytometer for multiparametric single cell mechanophenotyping is reported. The microfluidic platform integrates hydrodynamic cell pinching, and multifrequency impedance quantification of cell size, deformability, and membrane impedance (indicative of cell viability and activation). A newly-defined “electrical deformability index” is validated by numerical simulations, and shows strong correlations with the optical cell deformability index of HL-60 experimentally. Human neutrophils treated with various biochemical stimul are further profiled, and distinct differences in multimodal impedance signatures and UMAP analysis are observed. Overall, the integrated cytometer enables label-free cell profiling at throughput of >1000 cells min−1 without any antibodies labeling to facilitate clinical diagnostics.
AB - The intrinsic biophysical states of neutrophils are associated with immune dysfunctions in diseases. While advanced image-based biophysical flow cytometers can probe cell deformability at high throughput, it is nontrivial to couple different sensing modalities (e.g., electrical) to measure other critical cell attributes including cell viability and membrane integrity. Herein, an “optics-free” impedance-deformability cytometer for multiparametric single cell mechanophenotyping is reported. The microfluidic platform integrates hydrodynamic cell pinching, and multifrequency impedance quantification of cell size, deformability, and membrane impedance (indicative of cell viability and activation). A newly-defined “electrical deformability index” is validated by numerical simulations, and shows strong correlations with the optical cell deformability index of HL-60 experimentally. Human neutrophils treated with various biochemical stimul are further profiled, and distinct differences in multimodal impedance signatures and UMAP analysis are observed. Overall, the integrated cytometer enables label-free cell profiling at throughput of >1000 cells min−1 without any antibodies labeling to facilitate clinical diagnostics.
KW - biophysical phenotyping
KW - impedance cytometry
KW - neutrophil profiling
UR - http://www.scopus.com/inward/record.url?scp=85125649956&partnerID=8YFLogxK
U2 - 10.1002/smll.202104822
DO - 10.1002/smll.202104822
M3 - Article
C2 - 35253966
AN - SCOPUS:85125649956
SN - 1613-6810
VL - 18
JO - Small
JF - Small
IS - 18
M1 - 2104822
ER -