Determination of blood lithium-ion concentration using digital microfluidic whole-blood separation and preloaded...

Existing microfluidic technologies for blood tests have several limitations, including difficulties in integrating the sample preparation steps, such as blood dilution, and precise metering of tiny samples (microliter) for accurate downstream analyses on a chip. Digital microfluidics (DMF) is a liquid manipulation technique that can provide precise volume control of micro or nano-liter liquid droplets. Without using sensitive but complex detection methods for tiny droplets involving fluorescence, luminescence, and electrochemistry, this article presents a DMF device with embedded paper-based sensors to detect blood lithium-ion (Li⁺) concentration by colorimetry. Dielectrophoresis on the DMF device between two parallel planar electrodes separates plasma droplets (from tens to hundreds of nanoliters in volume) from undiluted whole blood (a few microliters) within 4 min with an efficiency exceeding 90%. The embedded paper sensors contain a detection reagent to absorb the DMF-transported plasma droplets. These droplets change the color of the paper sensors in accordance with the Li⁺ concentration. Subsequently, colorimetry is used to reveal the Li⁺ concentration via image analysis. The proposed method meets the detection-sensitivity requirement for clinical diagnosis of bipolar disorder, making the DMF device a potential therapeutic tool for rapid whole-blood Li⁺ detection.