A Microfluidic Liquid Biopsy Platform to Monitor Protein Biomarker Heterogeneity in Single Circulating Therapy‐Resistance Cancer Cell

• Published in: Advanced Sensor Research 2023-12, Vol.2 (12), p.n/a
• Main Authors: Ahmed, Emtiaz, Shanmugasundaram, Karthik Balaji, Li, Junrong, Behren, Andreas, Lobb, Richard, Möller, Andreas, Wuethrich, Alain, Dey, Shuvashis, Sina, Abu Ali Ibn, Trau, Matt
• Format: Article
• Language: English
• Subjects: Antibodies; Biomarkers; Biopsy; Blood; Cancer; Cells; circulating tumor cells; Drug resistance; Electrodes; Flow cytometry; Growth factors; Health services; Heterogeneity; Immunoassay; liquid biopsy; Lung cancer; Melanoma; microfluidic sensors; Microfluidics; Monitoring; Protein expression; Proteins; Raman spectra; surface‐enhanced Raman scattering; Telemedicine; Tumors
• ISSN: 2751-1219; 2751-1219
• DOI: 10.1002/adsr.202300059

Tumor cells display heterogenous molecular signatures during the course of cancer and create distinct tumor cell subpopulations which challenge effective therapeutic decisions. Detection and monitoring of these heterogenous molecular events at single cell level are imperative to identify tumor cell subpopulations and to engage the best therapeutic options for the individual patient. Herein, a microfluidic liquid biopsy platform to analyze circulating tumor cells (CTCs) at single cell level is reported. The individual CTCs are captured in an alternating current‐induced microfluidic platform and analyzed by using surface‐enhanced Raman scattering spectroscopy. This platform selectively captures single CTCs from the patient's peripheral blood mononuclear cells. Using cell line models and patient samples, it is shown that the assay can simultaneously detect multiple protein biomarkers on a single CTC. The platform can stratify the CTCs into different subpopulations based on their cancer‐associated protein signature changes in response to drug treatment. This enables the identification of CTC subpopulations that are probably not responding to treatment and may assist clinicians in specifically monitoring and eliminating therapy‐resistant cancer cells within a lesion. This single CTC monitoring chip will likely have high clinical importance in disease diagnosis and treatment monitoring, and advance the knowledge of cancer heterogeneity. The single circulating tumor cell analysis platform specifically captures and identifies multiple target biomarkers on the cell surface by a surface‐enhanced Raman scattering microfluidic system. By analysing the heterogeneous expression patterns of individual cells, this platform enables the identification of a specific subpopulation of cells with higher biomarker expression during treatment with potential for informed therapeutic decision making.