title: Molecular profiling of single circulating tumor cells from lung cancer patients.
abstract: Circulating tumor cells (CTCs) are established cancer biomarkers for the "liquid biopsy" of tumors. Molecular analysis of single CTCs, which recapitulate primary and metastatic tumor biology, remains challenging because current platforms have limited throughput, are expensive, and are not easily translatable to the clinic. Here, we report a massively parallel, multigene-profiling nanoplatform to compartmentalize and analyze hundreds of single CTCs. After high-efficiency magnetic collection of CTC from blood, a single-cell nanowell array performs CTC mutation profiling using modular gene panels. Using this approach, we demonstrated multigene expression profiling of individual CTCs from non-small-cell lung cancer (NSCLC) patients with remarkable sensitivity. Thus, we report a high-throughput, multiplexed strategy for single-cell mutation profiling of individual lung cancer CTCs toward minimally invasive cancer therapy prediction and disease monitoring.
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305.|Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Seung-Min
authors.identifier: 0000-0002-2123-6245
authors.initials: SM
authors.lastname: Park
authors.affiliation: Department of Electrical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Dawson J
authors.initials: DJ
authors.lastname: Wong
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Chin Chun
authors.initials: CC
authors.lastname: Ooi
authors.affiliation: Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305.|Department of Bioengineering, Stanford University, Stanford, CA 94305.|Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: David M
authors.initials: DM
authors.lastname: Kurtz
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305.|Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Ophir
authors.initials: O
authors.lastname: Vermesh
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305.|Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Amin
authors.initials: A
authors.lastname: Aalipour
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
authors.forename: Susie
authors.initials: S
authors.lastname: Suh
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305.
authors.forename: Kelsey L
authors.initials: KL
authors.lastname: Pian
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Chabon
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720.
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Mehran
authors.initials: M
authors.lastname: Jamali
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Carmen
authors.initials: C
authors.lastname: Say
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Justin N
authors.initials: JN
authors.lastname: Carter
authors.affiliation: Department of Bioengineering, University of California, Berkeley, CA 94720.
authors.forename: Luke P
authors.initials: LP
authors.lastname: Lee
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304.|Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Ware G
authors.initials: WG
authors.lastname: Kuschner
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Erich J
authors.initials: EJ
authors.lastname: Schwartz
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Shrager
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.|Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Neal
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.|Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wakelee
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305.|Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305.|Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305.|Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94305.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Diehn
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305; sgambhir@stanford.edu viswamnair@stanford.edu sxwang@stanford.edu.|Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.|Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94305.
authors.forename: Viswam S
authors.initials: VS
authors.lastname: Nair
authors.affiliation: Department of Electrical Engineering, Stanford University, Stanford, CA 94305; sgambhir@stanford.edu viswamnair@stanford.edu sxwang@stanford.edu.|Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305.|Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94305.
authors.forename: Shan X
authors.initials: SX
authors.lastname: Wang
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305; sgambhir@stanford.edu viswamnair@stanford.edu sxwang@stanford.edu.|Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA 94305.|Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, Palo Alto, CA 94305.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000473:pathology; D002452:Cell Count; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D044085:Microfluidics; D008875:Middle Aged; D009154:Mutation; D036103:Nanotechnology; D009360:Neoplastic Cells, Circulating; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059010:Single-Cell Analysis
chemical_list: D014408:Biomarkers, Tumor; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
keywords: circulating tumor cells; microfluidics; rare-cell sorting; reverse transcription-PCR; single-cell analysis