A Digital Microfluidic Device Integrated with Electrochemical Impedance Spectroscopy for Cell-Based Immunoassay

Abstract

The dynamic immune response to various diseases and therapies has been considered a promising indicator of disease status and therapeutic effectiveness. For instance, the human peripheral blood mononuclear cell (PBMC), as a major player in the immune system, is an important index to indicate a patient’s immune function. Therefore, establishing a simple yet sensitive tool that can frequently assess the immune system during the course of disease and treatment is of great importance. This study introduced an integrated system that includes an electrochemical impedance spectroscope (EIS)-based biosensor in a digital microfluidic (DMF) device, to quantify the PBMC abundance with minimally trained hands. Moreover, we exploited the unique droplet manipulation feature of the DMF platform and conducted a dynamic cell capture assay, which enhanced the detection signal by 2.4-fold. This integrated system was able to detect as few as 104 PBMCs per mL, presenting suitable sensitivity to quantify PBMCs. This integrated system is easy-to-operate and sensitive, and therefore holds great potential as a powerful tool to profile immune-mediated therapeutic responses in a timely manner, which can be further evolved as a point-of-care diagnostic device to conduct near-patient tests from blood samples.

Advances in Integration, Wearable Applications, and Artificial Intelligence of Biomedical Microfluidics Systems

“…A gold layer was deposited on an ITO substrate with electron-beam physical vapor deposition, peeled, etched to create IDEs, and finally coated with anti-45 on the gold IDEs to manufacture a biometric layer. The detection of different concentrations of PBMCs in dynamic and static cell culture modes was compared in this system, and the results showed that the dynamic mode had a higher sensitivity than the PBMCs in the static condition [104]. Both electrochemical biosensors and microfluidics have their specific benefits, so the rational integration of these two analytical devices will create greater functional platforms.…”

Droplet Detection and Sorting System in Microfluidics: A Review

“…Electrical impedance spectroscopy (EIS)-based detection utilizes the contrast of impedance between different objects to achieve the detection and has been widely applied in microfluidic systems to characterize particles and cells [ 54 , 55 , 56 , 57 , 58 ]. The typical detection setup contains planar sensing electrode patterns deposited on the glass substrate (sometimes with an inert interstitial layer to isolate electrodes from the solution, thereby reducing electrode polarization) underneath the microfluidic channel [ 59 ].…”

Recent Advances on Cell Culture Platforms for In Vitro Drug Screening and Cell Therapies: From Conventional to Microfluidic Strategies

“…The authors validated the system with two chemotherapeutic drugs, DDP and epirubicin (EPI), towards MDA‐MB‐231 breast cancer cells and MCF‐10A normal breast cells. Recently, Zhang and Liu [ 197 ] developed digital microfluidics, including an electrochemical impedance spectroscope (EIS)‐based biosensor to detect human peripheral blood mononuclear cells to profile immune‐mediated therapeutic responses.…”