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Identification and Drug Screening of Single Cells from Human Tumors on Semiconductor Chip for Cancer Precision
Wenhao Hui1,2, Ka-Meng Lei1,2, Yingying Liu1,2
1State Key Laboratory of Analog and Mixed-Signal VLSI, Institute of Microelectronics, University of Macau, Taipa, 999078, Macau.
Abstract:
Drug screening of primary tumor cells directly assesses the drug efficacy on specific tumors, promoting personalized cancer treatment. The application of a microfluidic platform has realized drug screening using a limited amount of biopsy samples for cancer precision medicine. However, all the techniques face an inevitable issue of not all the primary tumor cells being cancer cells. Here, a system is introduced that integrates single-cell identification and drug screening on one semiconductor chip so that both drug efficacy on cancer cells and drug toxicity on noncancerous cells can be obtained simultaneously. An integrated circuit is built on the semiconductor chip for single-cell electric impedance sensing (IC-ECIS) of ultra-weak signals for distinguishing cancer cells from noncancerous cells without affecting cell vitality. Single-cell identification is validated using breast, lung, and liver cell lines as well as liver cancer specimens from clinical patients. The accuracy on commercial cell lines is ≈80%, and the diagnostic results of tumor tissues are consistent with clinical pathology results. Drug screening is run on the same chip after single cell identification for dual evaluation of drug efficacy and toxicity in both breast cancer models and clinical liver cancer patients. The on-chip drug screening is confirmed with off-chip counterpart experiments in breast cell lines. The effectiveness or ineffectiveness of a drug screened on the IC-ECIS chip demonstrated consistency in the presence or absence of specific mutations in the drug-related genes determined via exome sequencing of individual liver tumors, validating the method for precision medicine.
Insights
This study introduces a semiconductor chip for simultaneous single-cell identification and drug screening. This system evaluates drug efficacy on cancer cells and toxicity on noncancerous cells, advancing personalized cancer medicine.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Personalized cancer treatment relies on drug screening of primary tumor cells.
- Microfluidic platforms enable drug screening with limited biopsy samples.
- Distinguishing cancer cells from noncancerous cells is crucial for accurate drug screening.
Purpose of the Study:
- To develop an integrated system for simultaneous single-cell identification and drug screening on a semiconductor chip.
- To enable dual evaluation of drug efficacy on cancer cells and toxicity on noncancerous cells.
- To validate the system's accuracy and consistency for precision medicine applications.
Main Methods:
- Integration of single-cell electric impedance sensing (IC-ECIS) on a semiconductor chip for cell identification.
- Utilizing ultra-weak signal detection for distinguishing cancer cells without affecting cell vitality.
- Performing on-chip drug screening and efficacy/toxicity evaluation, validated by off-chip experiments and exome sequencing.
Main Results:
- Single-cell identification accuracy of approximately 80% on cell lines, with diagnostic results consistent with clinical pathology for tumor tissues.
- Simultaneous evaluation of drug efficacy and toxicity on breast cancer models and clinical liver cancer patients.
- On-chip drug screening results showed consistency with genetic mutation analysis (exome sequencing).
Conclusions:
- The integrated semiconductor chip system enables accurate single-cell identification and simultaneous drug screening.
- This technology facilitates dual evaluation of drug efficacy and toxicity, crucial for personalized cancer therapy.
- The validated method supports precision medicine by aligning drug response with individual tumor genetics.
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