PMID- 27739521
OWN - NLM
STAT- MEDLINE
DCOM- 20180411
LR  - 20181202
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Oct 14
TI  - Label-free enumeration, collection and downstream cytological and cytogenetic 
      analysis of circulating tumor cells.
PG  - 35474
LID - 10.1038/srep35474 [doi]
LID - 35474
AB  - Circulating tumor cells (CTCs) have a great potential as indicators of metastatic 
      disease that may help physicians improve cancer prognostication, treatment and 
      patient outcomes. Heterogeneous marker expression as well as the complexity of 
      current antibody-based isolation and analysis systems highlights the need for 
      alternative methods. In this work, we use a microfluidic Vortex device that can 
      selectively isolate potential tumor cells from blood independent of cell surface 
      expression. This system was adapted to interface with three protein-marker-free 
      analysis techniques: (i) an in-flow automated image processing system to 
      enumerate cells released, (ii) cytological analysis using Papanicolaou (Pap) 
      staining and (iii) fluorescence in situ hybridization (FISH) targeting the ALK 
      rearrangement. In-flow counting enables a rapid assessment of the 
      cancer-associated large circulating cells in a sample within minutes to determine 
      whether standard downstream assays such as cytological and cytogenetic analyses 
      that are more time consuming and costly are warranted. Using our platform 
      integrated with these workflows, we analyzed 32 non-small cell lung cancer 
      (NSCLC) and 22 breast cancer patient samples, yielding 60 to 100% of the cancer 
      patients with a cell count over the healthy threshold, depending on the detection 
      method used: respectively 77.8% for automated, 60-100% for cytology, and 80% for 
      immunostaining based enumeration.
FAU - Dhar, Manjima
AU  - Dhar M
AD  - Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 
      Engineering V, P.O. Box 951600, Los Angeles, CA 90095, USA.
FAU - Pao, Edward
AU  - Pao E
AD  - Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 
      Engineering V, P.O. Box 951600, Los Angeles, CA 90095, USA.
FAU - Renier, Corinne
AU  - Renier C
AD  - Vortex Biosciences Inc., 1490 O'Brien Drive, Suite E, Menlo Park, CA 94025, USA.
AD  - Department of Surgery, Stanford University School of Medicine, MSLS Bldg, 1201 
      Welch Road, Stanford, CA 94305, USA.
FAU - Go, Derek E
AU  - Go DE
AD  - Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 
      Engineering V, P.O. Box 951600, Los Angeles, CA 90095, USA.
FAU - Che, James
AU  - Che J
AD  - Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 
      Engineering V, P.O. Box 951600, Los Angeles, CA 90095, USA.
AD  - Vortex Biosciences Inc., 1490 O'Brien Drive, Suite E, Menlo Park, CA 94025, USA.
FAU - Montoya, Rosita
AU  - Montoya R
AD  - Department of Pathology and Laboratory Medicine, University of California, Los 
      Angeles, Los Angeles, CA 90095, USA.
FAU - Conrad, Rachel
AU  - Conrad R
AD  - Department of Pathology and Laboratory Medicine, University of California, Los 
      Angeles, Los Angeles, CA 90095, USA.
FAU - Matsumoto, Melissa
AU  - Matsumoto M
AD  - Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 
      Engineering V, P.O. Box 951600, Los Angeles, CA 90095, USA.
FAU - Heirich, Kyra
AU  - Heirich K
AD  - Department of Surgery, Stanford University School of Medicine, MSLS Bldg, 1201 
      Welch Road, Stanford, CA 94305, USA.
FAU - Triboulet, Melanie
AU  - Triboulet M
AD  - Department of Surgery, Stanford University School of Medicine, MSLS Bldg, 1201 
      Welch Road, Stanford, CA 94305, USA.
FAU - Rao, Jianyu
AU  - Rao J
AD  - Department of Pathology and Laboratory Medicine, University of California, Los 
      Angeles, Los Angeles, CA 90095, USA.
AD  - Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA.
FAU - Jeffrey, Stefanie S
AU  - Jeffrey SS
AD  - Department of Surgery, Stanford University School of Medicine, MSLS Bldg, 1201 
      Welch Road, Stanford, CA 94305, USA.
FAU - Garon, Edward B
AU  - Garon EB
AD  - Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA.
AD  - UCLA Santa Monica Hematology Oncology, 2020 Santa Monica Blvd, Suite 600, Santa 
      Monica, CA 90404, USA.
FAU - Goldman, Jonathan
AU  - Goldman J
AD  - Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA.
AD  - UCLA Santa Monica Hematology Oncology, 2020 Santa Monica Blvd, Suite 600, Santa 
      Monica, CA 90404, USA.
FAU - Rao, Nagesh P
AU  - Rao NP
AD  - Department of Pathology and Laboratory Medicine, University of California, Los 
      Angeles, Los Angeles, CA 90095, USA.
FAU - Kulkarni, Rajan
AU  - Kulkarni R
AD  - Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA.
AD  - California NanoSystems Institute, 570 Westwood Plaza, Building 114, Los Angeles, 
      CA 90095, USA.
AD  - Division of Dermatology, UCLA Medical Center, 52-121 CHS, Los Angeles, CA 90095, 
      USA.
FAU - Sollier-Christen, Elodie
AU  - Sollier-Christen E
AD  - Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 
      Engineering V, P.O. Box 951600, Los Angeles, CA 90095, USA.
AD  - Vortex Biosciences Inc., 1490 O'Brien Drive, Suite E, Menlo Park, CA 94025, USA.
AD  - Department of Surgery, Stanford University School of Medicine, MSLS Bldg, 1201 
      Welch Road, Stanford, CA 94305, USA.
FAU - Di Carlo, Dino
AU  - Di Carlo D
AD  - Department of Bioengineering, University of California, 420 Westwood Plaza, 5121 
      Engineering V, P.O. Box 951600, Los Angeles, CA 90095, USA.
AD  - Vortex Biosciences Inc., 1490 O'Brien Drive, Suite E, Menlo Park, CA 94025, USA.
AD  - Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA.
AD  - California NanoSystems Institute, 570 Westwood Plaza, Building 114, Los Angeles, 
      CA 90095, USA.
LA  - eng
GR  - KL2 TR000122/TR/NCATS NIH HHS/United States
GR  - KL2 TR001882/TR/NCATS NIH HHS/United States
GR  - P30 CA016042/CA/NCI NIH HHS/United States
GR  - R33 CA177456/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161014
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Anaplastic Lymphoma Kinase
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Breast Neoplasms/*blood
MH  - Carcinoma, Non-Small-Cell Lung/*blood
MH  - Case-Control Studies
MH  - Cell Separation/instrumentation/*methods
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Lung Neoplasms/*blood
MH  - MCF-7 Cells
MH  - Male
MH  - Microfluidics/instrumentation/*methods
MH  - Neoplastic Cells, Circulating/*metabolism/pathology
MH  - Papanicolaou Test/methods
MH  - Receptor Protein-Tyrosine Kinases/genetics/metabolism
PMC - PMC5064381
COIS- Some of the authors (C.R., J.C., E.S.-C. and D.D.C) and the Regents of the 
      University of California have financial interests in Vortex Biosciences and 
      intellectual property described herein. J. G. serves on the scientific advisory 
      board of Vortex Biosciences.
EDAT- 2016/10/16 06:00
MHDA- 2018/04/12 06:00
PMCR- 2016/10/14
CRDT- 2016/10/15 06:00
PHST- 2015/10/27 00:00 [received]
PHST- 2016/09/28 00:00 [accepted]
PHST- 2016/10/15 06:00 [entrez]
PHST- 2016/10/16 06:00 [pubmed]
PHST- 2018/04/12 06:00 [medline]
PHST- 2016/10/14 00:00 [pmc-release]
AID - srep35474 [pii]
AID - 10.1038/srep35474 [doi]
PST - epublish
SO  - Sci Rep. 2016 Oct 14;6:35474. doi: 10.1038/srep35474.