ArticleScience advances2019
Covalent chemistry on nanostructured substrates enables noninvasive quantification of gene rearrangements in circulating tumor cells.
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Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Micro/Nanostructured Materials and Microfluidic Diagnostic Platforms Enable Multimodal Detection of Circulating Tumor Cells.Exploration (Beijing, China) · 2026Review
- Bioorthogonal Click Chemistry-Enabled Enrichment of Extracellular Vesicles for Integrated Molecular and Functional Liquid Biopsy§.Accounts of chemical research · 2026Article
- High-Viability Circulating Tumor Cells Sorting From Whole Blood at Single Cell Level Using Laser-Induced Forward Transfer-Assisted Microfiltration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Digital Quantitative Detection for Heterogeneous Protein and mRNA Expression Patterns in Circulating Tumor Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Recent advances in micro-/nanostructure array integrated microfluidic devices for efficient separation of circulating tumor cells.RSC advances · 2022Review
- Designer tetrahedral DNA framework-based microfluidic technology for multivalent capture and release of circulating tumor cells.Materials today. Bio · 2022Article
- Light-activated tetrazines enable precision live-cell bioorthogonal chemistry.Nature chemistry · 2022Article
- Circulating tumor cells: A step toward precision medicine in hepatocellular carcinoma.Journal of gastroenterology and hepatology · 2022Review
- Nanomaterial-Based Immunocapture Platforms for the Recognition, Isolation, and Detection of Circulating Tumor Cells.Frontiers in bioengineering and biotechnology · 2022Review
- Circulating trophoblast cell clusters for early detection of placenta accreta spectrum disorders.Nature communications · 2021Article
- Well-Defined Nanostructured Biointerfaces: Strengthened Cellular Interaction for Circulating Tumor Cells Isolation.Advanced healthcare materials · 2021Article
- Covalent Chemistry-Mediated Multimarker Purification of Circulating Tumor Cells Enables Noninvasive Detection of Molecular Signatures of Hepatocellular Carcinoma.Advanced materials technologies · 2021Article
- On-Chip Biogenesis of Circulating NK Cell-Derived Exosomes in Non-Small Cell Lung Cancer Exhibits Antitumoral Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Coupling Nanostructured Microchips with Covalent Chemistry Enables Purification of Sarcoma-Derived Extracellular Vesicles for Downstream Functional Studies.Advanced functional materials · 2020Article
- Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring.Nature communications · 2020Observational
- Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices.Micromachines · 2020Review
- A circulating tumor cell-based digital assay for the detection of EGFR T790M mutation in advanced non-small cell lung cancer.Journal of materials chemistry. B · 2020Article
- Nanostructured Substrates for Detection and Characterization of Circulating Rare Cells: From Materials Research to Clinical Applications.Advanced materials (Deerfield Beach, Fla.) · 2020Review
Corrections and comments
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Authors and funding
27 authors at 8 institutions in 3 countries.
Jiantong DongCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0001-7063-711X
Yu Jen JanCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-2962-2933
Ju ChengCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Ryan Y ZhangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-3122-4053
Meng MengCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-9715-6292
Matthew SmalleyCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Pin-Jung ChenCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Xinghong TangCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-2342-5058
Patrick TsengCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-6536-5647
Lirong BaoCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-6143-078X
Tzu-Yang HuangSmart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, Taipei 11529, Taiwan.
Dongjing ZhouDepartment of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510120, China.
Yupin LiuDepartment of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510120, China.
Xiaoshu ChaiDepartment of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510120, China.
Haibo ZhangDepartment of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510120, China.
Anqi ZhouCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0001-9358-3054
Vatche G AgopianDepartment of Surgery, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Edwin M PosadasUrologic Oncology Program and Uro-Oncology Research Laboratories, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.ORCID 0000-0001-8649-1346
Jing-Jong ShyueResearch Center for Applied Sciences, Academia Sinica, Taipei 11529, Taiwan.ORCID 0000-0002-8508-659X
Steven J JonasDepartment of Pediatrics, David Geffen School of Medicine, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and Children's Discovery and Innovation Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-8111-0249
Paul S WeissCalifornia NanoSystems Institute, Departments of Chemistry and Biochemistry and Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0001-5527-6248
Mengyuan LiBeijing National Laboratory for Molecular Sciences, MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.ORCID 0000-0002-4664-1845
Guangjuan ZhengDepartment of Pathology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou 510120, China.ORCID 0000-0001-5570-2470
Hsiao-Hua YuSmart Organic Materials Laboratory, Institute of Chemistry, Academia Sinica, Taipei 11529, Taiwan.ORCID 0000-0002-3603-6932
Meiping ZhaoBeijing National Laboratory for Molecular Sciences, MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.ORCID 0000-0002-8696-8738
Hsian-Rong TsengCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0003-0942-5905
Yazhen ZhuCalifornia NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-2130-8085
California NanoSystems Institute · USGuangzhou University of Chinese Medicine · CNCedars-Sinai Medical Center · USInstitute of Chemistry, Academia Sinica · TWPeking University · CNBroad Center · USResearch Center for Applied Science, Academia Sinica · TWUniversity of California, Los Angeles · US
Funding
Non-Invasive Prenatal Diagnostics Based on Circulating TrophoblastsU01EB026421 · NIBIB · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PISARSKA, MARGARETA, TSENG, HSIAN-RONG · 2019 to 2023
$4.0MA blood test to identify prostate cancer patients at risk for visceral metastasisR01CA218356 · NCI · CEDARS-SINAI MEDICAL CENTER · PI POSADAS, EDWIN MELENCIO, TSENG, HSIAN-RONG · 2017 to 2021
$3.0MIntegrated analysis of HCC CTCs for Liver Transplant Candidate SelectionR01CA246304 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGOPIAN, VATCHE, TSENG, HSIAN-RONG · 2020 to 2024
$2.8MThermoresponsive NanoVelcro CTC Purification System for Prostate Cancer ProfilingU01CA198900 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI POSADAS, EDWIN MELENCIO, TSENG, HSIAN-RONG · 2015 to 2019
$2.4MCTC Purification System Based on Thermoresponsive NanoSubstratesR44CA180482 · NCI · CYTOLUMINA TECHNOLOGIES CORPORATION, INC · PI LIU, SEAN XIAO, TSENG, HSIAN-RONG · 2015 to 2016
$2.0MMolecular and Functional Analysis of Single Circulating Melanoma CellsR33CA174562 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TSENG, HSIAN-RONG · 2013 to 2015
$987kClick Chemistry-Mediated Microfluidic Sorting for HCC CTCsR21CA235340 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AGOPIAN, VATCHE, TSENG, HSIAN-RONG · 2019 to 2021
$543kA Microchip with Thermally Responsive Polymers for Capture and Recovery of CTCsR43CA180482 · NCI · CYTOLUMINA TECHNOLOGIES CORPORATION, INC · PI GARCIA, MITCH · 2013 to 2013
$200kNCI NIH HHS R01 CA218356NCI NIH HHS R01 CA246304NCI NIH HHS R21 CA235340NCI NIH HHS R33 CA174562NCI NIH HHS R43 CA180482NCI NIH HHS R44 CA180482NCI NIH HHS U01 CA198900NIBIB NIH HHS U01 EB026421
Abstract
Well-preserved mRNA in circulating tumor cells (CTCs) offers an ideal material for conducting molecular profiling of tumors, thereby providing a noninvasive diagnostic solution for guiding treatment intervention and monitoring disease progression. However, it is technically challenging to purify CTCs while retaining high-quality mRNA.Here, we demonstrate a covalent chemistry-based nanostructured silicon substrate ("Click Chip") for CTC purification that leverages bioorthogonal ligation-mediated CTC capture and disulfide cleavage-driven CTC release. This platform is ideal for CTC mRNA assays because of its efficient, specific, and rapid purification of pooled CTCs, enabling downstream molecular quantification using reverse transcription Droplet Digital polymerase chain reaction. Rearrangements of ALK/ROS1 were quantified using CTC mRNA and matched with those identified in biopsy specimens from 12 patients with late-stage non-small cell lung cancer. Moreover, CTC counts and copy numbers of ALK/ROS1 rearrangements could be used together for evaluating treatment responses and disease progression.
Indexed as
AdultAgedAnaplastic Lymphoma KinaseCarcinoma, Non-Small-Cell LungCell Line, TumorClick ChemistryFemaleGene RearrangementHumansMaleMiddle AgedNanostructuresNeoplasm StagingNeoplastic Cells, CirculatingProtein-Tyrosine KinasesProto-Oncogene ProteinsALK protein, humanAnaplastic Lymphoma KinaseProtein-Tyrosine KinasesProto-Oncogene ProteinsRNA, MessengerROS1 protein, humanSilicon
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