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Towards an optimal and unbiased approach for tumor cell isolation

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Abstract

Our current understanding of clinical significance or the lack thereof of circulating tumor cells (CTCs) is biased by the technology used to isolate these rare cells. Despite the presence of a vast number of academic and commercial technologies, the lack of a standardized and optimized platform has been widely noted. We present a negative enrichment approach, integrating WBC depletion and chemical-free RBC depletion in the same setup without the need for centrifugation, washing or multiple sample handling steps. This approach achieves an average of >90 % recovery of spiked tumor cells and >99 % total WBC depletion in whole blood across multiple cell lines, in a simple and easy-to-use assay. The results presented herein and ongoing improvements aim to fulfill the need for a highly reliable, unbiased, standardized, and optimized CTC isolation platform, using component technologies that are validated for cell isolation.

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Abbreviations

CTC:

Circulating tumor cells

WBC:

White blood cell

RBC:

Red blood cell

EMT:

Epithelial to mesenchymal transition

TAC:

Tetrameric Antibody Complexes

GFP:

Green florescent protein

PBS:

Phosphate Buffered Saline

EpCAM:

Epithelial cell adhesion molecule

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Acknowledgments

This work was supported by the Science and Engineering Research Council of A*STAR (Agency for Science, Technology and Research), Singapore under the grant number 1031490005. In addition, we greatly appreciate the support from Dr. Chaitanya Kantak for microslit membrane fabrication.

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Authors and Affiliations

  1. BioElectronics Programme, Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 1 Science Park Road, Singapore, 117528, Singapore

    Bhuvanendran Nair Gourikutty Sajay, Chia-Pin Chang, Hamizah Ahmad & Wong Chee Chung

  2. Division of Microelectronics, School of Electrical and Electronics Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore

    Bhuvanendran Nair Gourikutty Sajay & Poenar Daniel Puiu

  3. BioElectronics Programme, Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 11 Science Park Road, Singapore, 117685, Singapore

    Abdur Rub Abdur Rahman

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  1. Bhuvanendran Nair Gourikutty Sajay
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  2. Chia-Pin Chang
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  3. Hamizah Ahmad
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  4. Wong Chee Chung
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  5. Poenar Daniel Puiu
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  6. Abdur Rub Abdur Rahman
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Correspondence to Bhuvanendran Nair Gourikutty Sajay or Abdur Rub Abdur Rahman.

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Bhuvanendran Nair Gourikutty Sajay and Chia-Pin Chang contributed equally to this paper.

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Sajay, B.N.G., Chang, CP., Ahmad, H. et al. Towards an optimal and unbiased approach for tumor cell isolation. Biomed Microdevices 15, 699–709 (2013). https://doi.org/10.1007/s10544-013-9757-9

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