TY - JOUR
T1 - Precision microfilters as an all in one system for multiplex analysis of circulating tumor cells
AU - Adams, Daniel L.
AU - Alpaugh, R. Katherine
AU - Martin, Stuart S.
AU - Charpentier, Monica
AU - Chumsri, Saranya
AU - Cristofanilli, Massimo
AU - Adams, Diane K.
AU - Makarova, Olga V.
AU - Zhu, Peixuan
AU - Li, Shuhong
AU - Tang, Cha Mei
AU - Stefansson, Steingrimur
N1 - Publisher Copyright:
© The Royal Society of Chemistry 2016.
PY - 2016
Y1 - 2016
N2 - Enumeration of circulating tumor cells (CTCs) from cancer patient blood is an established diagnostic assay used to evaluate patient status as a singleplex test. However, in the coming age of personalized medicine, multiplex analysis of patient CTCs, including proteomic and genomic techniques, will have to be integrated with CTC isolation platform technologies. Advancements in microfabrication have demonstrated that CTCs can be isolated and analyzed using microfluidic lab-on-a-chip devices. However, to date, most microfluidic devices are either still in the development phase, not applicable to all clinical tests, or are not commercially available. To overcome these discrepancies, we describe an all-in-one device for the isolation and multiplexing of clinically applicable CTC assays. Microfilters present an ideal lab-on-a-chip platform for analysis of CTCs as non-toxic and inert materials allow for a multitude of tests from cell growth through clinical staining techniques, all without background interference. Lithographically fabricated microfilters, can be made with high porosity, precise pore dimensions, arrayed pore distribution, and optimized for CTC size-based isolation. In this study we describe microfilter use in isolation and in situ analysis of CTCs using multiple sequential techniques including culture, FISH, histopathological analysis, H&E staining, photobleaching and re-staining. Further, as a proof of principle, we then describe the ability to quantitatively release patient derived CTCS from the microfilters for potential use in downstream genomic/proteomic analysis.
AB - Enumeration of circulating tumor cells (CTCs) from cancer patient blood is an established diagnostic assay used to evaluate patient status as a singleplex test. However, in the coming age of personalized medicine, multiplex analysis of patient CTCs, including proteomic and genomic techniques, will have to be integrated with CTC isolation platform technologies. Advancements in microfabrication have demonstrated that CTCs can be isolated and analyzed using microfluidic lab-on-a-chip devices. However, to date, most microfluidic devices are either still in the development phase, not applicable to all clinical tests, or are not commercially available. To overcome these discrepancies, we describe an all-in-one device for the isolation and multiplexing of clinically applicable CTC assays. Microfilters present an ideal lab-on-a-chip platform for analysis of CTCs as non-toxic and inert materials allow for a multitude of tests from cell growth through clinical staining techniques, all without background interference. Lithographically fabricated microfilters, can be made with high porosity, precise pore dimensions, arrayed pore distribution, and optimized for CTC size-based isolation. In this study we describe microfilter use in isolation and in situ analysis of CTCs using multiple sequential techniques including culture, FISH, histopathological analysis, H&E staining, photobleaching and re-staining. Further, as a proof of principle, we then describe the ability to quantitatively release patient derived CTCS from the microfilters for potential use in downstream genomic/proteomic analysis.
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U2 - 10.1039/c5ra21524b
DO - 10.1039/c5ra21524b
M3 - Article
AN - SCOPUS:84955458423
SN - 2046-2069
VL - 6
SP - 6405
EP - 6414
JO - RSC Advances
JF - RSC Advances
IS - 8
ER -