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Dielectrophoresis-Based SERS Sensors for the Detection of Cancer Cells in Microfluidic Chips.

ABSTRACT: The detection of freely circulating cancer cells (CTCs) is one of the greatest challenges of modern medical diagnostics. For several years, there has been increased attention on the use of surface-enhanced Raman spectroscopy (SERS) for the detection of CTCs. SERS is a non-destructive, accurate and precise technique, and the use of special SERS platforms even enables the amplification of weak signals from biological objects. In the current study, we demonstrate the unique arrangement of the SERS technique combined with the deposition of CTCs cells on the surface of the SERS platform via a dielectrophoretic effect. The appropriate frequencies of an alternating electric field and a selected shape of the electric field can result in the efficient deposition of CTCs on the SERS platform. The geometry of the microfluidic chip, the type of the cancer cells and the positive dielectrophoretic phenomenon resulted in the trapping of CTCs on the surface of the SERS platform. We presented results for two type of breast cancer cells, MCF-7 and MDA-MB-231, deposited from the 0.1 PBS solution. The limit of detection (LOD) is 20 cells/mL, which reflects the clinical potential and usefulness of the developed approach. We also provide a proof-of-concept for these CTCs deposited on the SERS platform from blood plasma.

SUBMITTER: Szymborski TR

PROVIDER: S-EPMC9496591 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Dielectrophoresis-Based SERS Sensors for the Detection of Cancer Cells in Microfluidic Chips.

Szymborski Tomasz R TR Czaplicka Marta M Nowicka Ariadna B AB Trzcińska-Danielewicz Joanna J Girstun Agnieszka A Kamińska Agnieszka A

Biosensors 20220825 9

The detection of freely circulating cancer cells (CTCs) is one of the greatest challenges of modern medical diagnostics. For several years, there has been increased attention on the use of surface-enhanced Raman spectroscopy (SERS) for the detection of CTCs. SERS is a non-destructive, accurate and precise technique, and the use of special SERS platforms even enables the amplification of weak signals from biological objects. In the current study, we demonstrate the unique arrangement of the SERS ...[more]

PMID: 36140065

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Project description:BackgroundsDetecting free cancer cells from ascites and peritoneal lavages is crucial for diagnosing gastric cancer (GC). However, traditional methods are limited for early-stage diagnosis due to their low sensitivity.MethodsA label-free, rapid, and high-throughput technique was developed for separating cancer cells from ascites and peritoneal lavages using an integrated microfluidic device, taking advantage of dean flow fractionation and deterministic lateral displacement. Afterward, separated cells were analyzed using a microfluidic single-cell trapping array chip (SCTA-chip). In situ immunofluorescence for EpCAM, YAP-1, HER-2, CD45 molecular expressions, and Wright-Giemsa staining were performed for cells in SCTA-chips. At last, YAP1 and HER-2 expression in tissues was analyzed by immunohistochemistry.FindingsThrough integrated microfluidic device, cancer cells were successfully separated from simulated peritoneal lavages containing 1/10,000 cancer cells with recovery rate of 84.8% and purity of 72.4%. Afterward, cancer cells were isolated from 12 patients' ascites samples. Cytological examinations showed cancer cells were efficiently enriched with background cells excluded. Afterwards, separated cells from ascites were analyzed by SCTA-chips, and recognized as cancer cells through EpCAM+/CD45- expression and Wright-Giemsa staining. Interestingly, 8 out of 12 ascites samples showed HER-2+ cancer cells. At last, the results through a serial expression analysis showed that YAP1 and HER-2 have discordant expression during metastasis.InterpretationMicrofluidic Chips developed in our study could not only rapidly detect label-free free GC cells in ascites and peritoneal lavages with high-throughput, they could also analyze ascites cancer cells at the single-cell level, improving peritoneal metastasis diagnosis and investigation of therapeutic targets.FundingThis research was supported by National Natural Science Foundation of China (22134004, U1908207, 91859111); Natural Science Foundation of Shandong Province of China (ZR2019JQ06); Taishan Scholars Program of Shandong Province tsqn (201909077); Local Science and Technology Development Fund Guided by the Central Government (YDZX20203700002568); Applied Basic Research Program of Liaoning Province (2022020284-JH2/1013).

Dataset Information

Dielectrophoresis-Based SERS Sensors for the Detection of Cancer Cells in Microfluidic Chips.

Publications

Dielectrophoresis-Based SERS Sensors for the Detection of Cancer Cells in Microfluidic Chips.

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