scholarly journals Enhancing sensitivity and specificity in rare cell capture microdevices with dielectrophoresis

2015 ◽  
Vol 9 (1) ◽  
pp. 014116 ◽  
Author(s):  
James P. Smith ◽  
Chao Huang ◽  
Brian J. Kirby
Lab on a Chip ◽  
2015 ◽  
Vol 15 (10) ◽  
pp. 2240-2247 ◽  
Author(s):  
Joseph D'Silva ◽  
Robert H. Austin ◽  
James C. Sturm

Disabling of mechanisms driving clot formation in deterministic lateral displacement arrays allows rare cell capture from large volumes of blood.


2018 ◽  
Vol 24 (11) ◽  
pp. 2539-2547 ◽  
Author(s):  
Ja Hye Myung ◽  
Michael J. Eblan ◽  
Joseph M. Caster ◽  
Sin-Jung Park ◽  
Michael J. Poellmann ◽  
...  

2015 ◽  
Vol 108 (2) ◽  
pp. 630a-631a
Author(s):  
Chwee Teck Lim

Lab on a Chip ◽  
2012 ◽  
Vol 12 (23) ◽  
pp. 4972 ◽  
Author(s):  
Jason G Kralj ◽  
Chandamany Arya ◽  
Alessandro Tona ◽  
Thomas P Forbes ◽  
Matthew S Munson ◽  
...  

2012 ◽  
Vol 33 (21) ◽  
pp. 3133-3142 ◽  
Author(s):  
James P. Smith ◽  
Alexander C. Barbati ◽  
Steven M. Santana ◽  
Jason P. Gleghorn ◽  
Brian J. Kirby

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 721-721
Author(s):  
Hamid Emamekhoo ◽  
Jennifer L. Schehr ◽  
Rory M. Bade ◽  
Xiao X. Wei ◽  
Rana R. McKay ◽  
...  

721 Background: Despite therapeutic advancement in Vascular endothelial growth factor receptor (VEGF-R) tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) for mRCC treatment, there is currently no reliable predictive biomarkers of response or resistance. Single site biopsies provide limited information given the heterogenous nature of mRCC. Liquid biopsies may overcome these limitations; however, prior CTC capture platforms lacked sufficient sensitivity and specificity to achieve clinically useful detection rates. Methods: Given the prevalence of VEGF dependency, and its reliance on hypoxia, we aimed to increase sensitivity and specificity of capturing and identifying mRCC CTCs using carbonic anhydrase IX (CA IX) and CA XII. In addition, traditional markers for cell capture and identification with epithelial cellular adhesion molecule (EpCAM) and cytokeratin (CK) were included. Exclusion-based Sample Preparation technology was used to maximize cell yield. CD45/34/66b positive blood cells were excluded to ensure high specificity in evaluation of PD-L1 and HLA I expression on CTCs. Results: In a preliminary cohort of 21 mRCC pts (treatment: TKI=12, ICI=5, TKI+ICI=2, baseline=2), we identified heterogeneous populations of CTCs with differential expression of CA XII and CK. We detected CK+ CTCs in 20/21 pts (mean= 5/mL; range 0-53), CAXII+ CTCs in 21/21 pts (mean= 1/mL; range 1-9), and CK+/CAXII+ CTCs in 19/21 pts (mean=7/mL; range 0-102). In pts with multiple CTC samples on treatment, there was a high correlation between the number of CK+ CTCs and treatment response (ROC AUC 0.88). PD-L1 expression in CAXII+ CTCs correlated with response to ICI (ROC AUC 0.77) and TKI (ROC AUC 0.73). HLA I expression in CAXII+ CTCs correlated with response to TKI (ROC AUC 0.73) better than ICI (ROC AUC 0.59). Conclusions: Assessment of CTC heterogeneity may provide valuable molecular insights and diversify tools for early detection of therapeutic response and resistance that may guide treatment decision making. This assay is being tested in ongoing Phase II clinical trials.


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