A digital microfluidic device integrated with electrochemical sensor and 3D matrix for detecting soluble PD-L1
Yuqian Zhang1,2, Jing Liu1,2, Ting-Wen Lo1,2
1Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA.
Abstract:
PD1/PD-L1 checkpoint inhibitors are at the forefront of cancer immunotherapies. However, the overall response rate remains only 10-30%. Even among initial responders, drug resistance often occurs, which can lead to prolonged use of a futile therapy in the race with the fatal disease. It would be ideal to closely monitor key indicators of patients' immune responsiveness, such as circulating PD-L1 levels. Traditional PD-L1 detection methods, such as ELISA, are limited in sensitivity and rely on core lab facilities, preventing their use for the regular monitoring. Electrochemical sensors exist as an attractive candidate for point-of-care tool, yet, streamlining multiple processes in a single platform remains a challenge. To overcome this challenge, this work integrated electrochemical sensor arrays into a digital microfluidic device to combine their distinct merits, so that soluble PD-L1 (sPD-L1) molecules can be rapidly detected in a programmed and automated manner. This new platform featured microscale electrochemical sensor arrays modified with electrically conductive 3D matrix, and can detect as low as 1 pg/mL sPD-L1 with high specificity. The sensors also have desired repeatability and can obtain reproducible results on different days. To demonstrate the functionality of the device to process more complex biofluids, we used the device to detect sPD-L1 molecules secreted by human breast cancer cell line in culture media directly and observed 2X increase in signal compared with control experiment. This novel platform holds promise for the close monitoring of sPD-L1 level in human physiological fluids to evaluate the efficacy of PD-1/PD-L1 immunotherapy.
Insights
This study presents a novel microfluidic device with electrochemical sensors for rapid, sensitive detection of soluble PD-L1 (sPD-L1). This technology can help monitor cancer immunotherapy effectiveness and detect drug resistance early.
Area of Science:
- Biomedical Engineering
- Immunology
- Analytical Chemistry
Background:
- PD-1/PD-L1 checkpoint inhibitors are crucial cancer immunotherapies, but response rates are low (10-30%) and drug resistance is common.
- Monitoring immune responsiveness via soluble PD-L1 (sPD-L1) is vital, but traditional methods like ELISA lack sensitivity and point-of-care applicability.
- Existing electrochemical sensors offer potential for point-of-care diagnostics, yet integrating multiple functions into a single platform remains a challenge.
Purpose of the Study:
- To develop an integrated digital microfluidic device with electrochemical sensor arrays for automated and rapid detection of soluble PD-L1 (sPD-L1).
- To overcome limitations of traditional detection methods and enable close monitoring of patient immune responsiveness during cancer immunotherapy.
Main Methods:
- Integration of microscale electrochemical sensor arrays, modified with conductive 3D matrices, into a digital microfluidic platform.
- Development of a programmed and automated system for rapid sPD-L1 detection in physiological fluids.
- Validation of the platform's sensitivity, specificity, and reproducibility using cultured human breast cancer cell line media.
Main Results:
- The novel platform achieved high sensitivity, detecting sPD-L1 down to 1 pg/mL with high specificity.
- The electrochemical sensors demonstrated excellent repeatability and reproducible results across different days.
- The device successfully detected sPD-L1 secreted by a human breast cancer cell line, showing a 2X signal increase compared to controls.
Conclusions:
- This integrated digital microfluidic device offers a promising solution for sensitive, rapid, and automated sPD-L1 detection.
- The platform holds potential for real-time monitoring of PD-1/PD-L1 immunotherapy efficacy and early identification of drug resistance.
- This technology could significantly advance point-of-care diagnostics for cancer immunotherapy management.
