Single-Cell Isolation Microfluidic Chip Based on Thermal Bubble Micropump Technology.

The isolation of single cells is essential for the development of single cell analysis methods, such as single-cell sequencing, monoclonal antibodies, and drug development. Traditional single-cell isolation techniques include flow cytometry (FACS), laser capture microdissection (LCM), micromanipulation, etc., but their operations are complex and have low throughput. Here, we present a microfluidic chip that can isolate individual cells from cell suspension and release them onto a well plate. It uses thermal bubble micropump technology to drive the fluid flow, and single-cell isolation is achieved by matching the flow resistance of the flow channel. Therefore, injection pumps and peristaltic pumps are not required for cell loading. Because of its small size, we can integrate hundreds of single-cell functional modules, which makes high-throughput single-cell isolation possible. For polystyrene beads, the capture rate of the single bead is close to 100%. Finally, the method has been applied to cells, and the capture rate of the single cell is also about 75%. This is a promising method for single-cell isolation.

A Smart Active Phase-Change Micropump Based on CMOS-MEMS Technology.

The rational integration of many microfluidic chips and micropumps remains challenging. Due to the integration of the control system and sensors in active micropumps, they have unique advantages over passive micropumps when integrated into microfluidic chips. An active phase-change micropump based on complementary metal-oxide-semiconductor-microelectromechanical system (CMOS-MEMS) technology was fabricated and studied theoretically and experimentally. The micropump structure is simple and consists of a microchannel, a series of heater elements along the microchannel, an on-chip control system, and sensors. A simplified model was established to analyze the pumping effect of the traveling phase transition in the microchannel. The relationship between pumping conditions and flow rate was examined. Based on the experimental results, the maximum flow rate of the active phase-change micropump at room temperature is 22 µL/min, and long-term stable operation can be achieved by optimizing heating conditions.

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

Microfluidics attracts much attention due to its multiple advantages such as high throughput, rapid analysis, low sample volume, and high sensitivity. Microfluidics has profoundly influenced many fields including chemistry, biology, medicine, information technology, and other disciplines. However, some stumbling stones (miniaturization, integration, and intelligence) strain the development of industrialization and commercialization of microchips. The miniaturization of microfluidics means fewer samples and reagents, shorter times to results, and less footprint space consumption, enabling a high throughput and parallelism of sample analysis. Additionally, micro-size channels tend to produce laminar flow, which probably permits some creative applications that are not accessible to traditional fluid-processing platforms. The reasonable integration of biomedical/physical biosensors, semiconductor microelectronics, communications, and other cutting-edge technologies should greatly expand the applications of current microfluidic devices and help develop the next generation of lab-on-a-chip (LOC). At the same time, the evolution of artificial intelligence also gives another strong impetus to the rapid development of microfluidics. Biomedical applications based on microfluidics normally bring a large amount of complex data, so it is a big challenge for researchers and technicians to analyze those huge and complicated data accurately and quickly. To address this problem, machine learning is viewed as an indispensable and powerful tool in processing the data collected from micro-devices. In this review, we mainly focus on discussing the integration, miniaturization, portability, and intelligence of microfluidics technology.

A Self-Regulated Microfluidic Device with Thermal Bubble Micropumps.

Currently, many microchips must rely on an external force (such as syringe pump, electro-hydrodynamic pump, and peristaltic pump, etc.) to control the solution in the microchannels, which probably adds manual operating errors, affects the accuracy of fluid manipulation, and enlarges the noise of signal. In addition, the reasonable integration of micropump and microchip remain the stumbling block for the commercialization of microfluidic technique. To solve those two problems, we designed and fabricated a thermal bubble micropump based on MEMS (micro-electro-mechanical systems) technique. Many parameters (voltage, pulse time, cycle delay time, etc.) affecting the performance of this micropump were explored in this work. The experimental results showed the flow rate of solution with the assistance of a micropump reached more than 15 µL/min in the optimal condition. Finally, a method about measuring total aflatoxin in Chinese herbs was successfully developed based on the integrated platform contained competitive immunoassay and our micropump-based microfluidics. Additionally, the limit of detection in quantifying total aflatoxin (AF) was 0.0615 pg/mL in this platform. The data indicate this combined technique of biochemical assays and micropump based microchip have huge potential in automatically, rapidly, and sensitively measuring other low concentration of biochemical samples with small volume.