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Expansion of patient-derived circulating tumor cells from liquid biopsies using a CTC microfluidic culture device.

Authors
  • Khoo, Bee Luan1
  • Grenci, Gianluca2, 3
  • Lim, Ying Bena3
  • Lee, Soo Chin4, 5
  • Han, Jongyoon1, 6, 7
  • Lim, Chwee Teck1, 2, 3, 8
  • 1 BioSystems and Micromechanics (BioSyM) IRG, Singapore-MIT Alliance for Research and Technology (SMART) Centre, Singapore, Singapore. , (Singapore)
  • 2 Mechanobiology Institute, National University of Singapore, Singapore, Singapore. , (Singapore)
  • 3 Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore. , (Singapore)
  • 4 Department of Hematology-Oncology, National University Cancer Institute, National University Hospital, Singapore, Singapore. , (Singapore)
  • 5 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. , (Singapore)
  • 6 Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • 7 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
  • 8 Department of Mechanical Engineering, National University of Singapore, Singapore, Singapore. , (Singapore)
Type
Published Article
Journal
Nature protocols
Publication Date
Jan 01, 2018
Volume
13
Issue
1
Pages
34–58
Identifiers
DOI: 10.1038/nprot.2017.125
PMID: 29215634
Source
Medline
License
Unknown

Abstract

The development of personalized cancer therapy depends on a robust system to monitor the patient's individual response to anticancer treatment. Anticancer drug efficacy has been tested on circulating tumor cells (CTCs) derived from patient blood samples after ex vivo expansion into CTC clusters. Current attempts to culture these primary cancer cells focus on long-term maintenance under growth factor supplements into cell lines, which usually takes >6 months and results in a CTC expansion efficiency of <20%. We recently developed a simple but unique microfluidics-based culture approach that requires minimal preprocessing (∼30 min) and does not require prior enrichment of CTCs or depend on the use of growth factor supplements. The approach capitalizes on co-culture of immune cells from the same patient blood sample within specially designed microwells that promote CTC cluster formation within 2 weeks, with an overall cluster formation success rate of ∼50%. Drug screening is facilitated by the incorporation of a gradient generator for parallel exposure to two or more drugs at various concentrations. Owing to the cost-effectiveness and less-invasive nature of this procedure, routine monitoring of disease progression can be achieved. The described microfluidics system can be operated with a single syringe pump to introduce drug compounds (which takes ∼6 min), followed by incubation of the CTC clusters for 48 h before analysis. In addition to its applications in biomedical research, the rapid readout of our platform will enable clinicians to assess or predict a patient's response to various therapeutic strategies, so as to enable personalized or precision therapy.

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