Concepts, electrode configuration, characterization, and data analytics of electric and electrochemical microfluidic platforms: a review.

Microfluidic cytometry (MC) and electrical impedance spectroscopy (EIS) are two important techniques in biomedical engineering. Microfluidic cytometry has been utilized in various fields such as stem cell differentiation and cancer metastasis studies, and provides a simple, label-free, real-time method for characterizing and monitoring cellular fates. The impedance microdevice, including impedance flow cytometry (IFC) and electrical impedance spectroscopy (EIS), is integrated into MC systems. IFC measures the impedance of individual cells as they flow through a microfluidic device, while EIS measures impedance changes during binding events on electrode regions. There have been significant efforts to improve and optimize these devices for both basic research and clinical applications, based on the concepts, electrode configurations, and cell fates. This review outlines the theoretical concepts, electrode engineering, and data analytics of these devices, and highlights future directions for development.

Immunomagnetic separation in a novel cavity-added serpentine microchannel structure for the selective isolation of lung adenocarcinoma cells.

The manipulation and separation of circulating tumor cells (CTCs) in continuous fluidic flows play an essential role in various biomedical applications, particularly the early diagnosis and treatment of diseases. Recent advances in magnetic bead development have provided promising solutions to the challenges encountered in CTC manipulation and isolation. In this study, we proposed a biomicrofluidic platform for specifically isolating human lung carcinoma A549 cells in microfluidic channels. The principle of separation was based on the effect of the magnetic field on aptamer-conjugated magnetic beads, also known as immunomagnetic beads, in a serpentine microchannel with added cavities (SMAC). The magnetic cell separation performance of the proposed structure was modeled and simulated by using COMSOL Multiphysics. The experimental procedures for aptamer molecular conjugation on 1.36 µm-diameter magnetic beads and magnetic bead immobilization on A549 cells were also reported. The lung carcinoma cell-bead complexes were then experimentally separated by an external magnetic field. Separation performance was also confirmed by optical microscopic observations and fluorescence analysis, which showed the high selectivity and efficiency of the proposed system in the isolation and capture of A549 cells in our proposed SMAC. At the flow rate of 5 µL/s, the capture rate of human lung carcinoma cells exceeded 70% in less than 15 min, whereas that of the nontarget cells was approximately 4%. The proposed platform demonstrated its potential for high selectivity, portability, and facile operation, which are suitable considerations for developing point-of-care applications for various biological and clinical purposes.

Biological Living Cell in-Flow Detection Based on Microfluidic Chip and Compact Signal Processing Circuit.

Detection and counting of biological living cells in continuous fluidic flows play an essential role in many applications for early diagnosis and treatment of diseases. In this regard, this study highlighted the proposal of a biochip system for detecting and enumerating human lung carcinoma cell flow in the microfluidic channel. The principle of detection was based on the change of impedance between sensing electrodes integrated in the fluidic channel, due to the presence of a biological cell in the sensing region. A compact electronic module was built to sense the unbalanced impedance between the sensing microelectrodes. It consisted of an instrumentation amplifier stage to obtain the difference between the acquired signals, and a lock-in amplifier stage to demodulate the signals at the stimulating frequency as well as to reject noise at other frequencies. The performance of the proposed system was validated through experiments of A549 cells detection as they passed over the microfluidic channel. The experimental results indicated the occurrence of large spikes (up to approximately 180 mV) over the background signal according to the passage of a single A549 cell in the continuous flow. The proposed device is simple-to-operate, inexpensive, portable, and exhibits high sensitivity, which are suitable considerations for developing point-of-care applications.

A compact microfluidic chip with integrated impedance biosensor for protein preconcentration and detection.

In this study, a low-cost, compact biochip is designed and fabricated for protein detection. Nanofractures formed by self-assembled gold nanoparticles at junction gaps are applied for ion enrichment and depletion to create a trapping zone when electroosmotic flow occurs in microchannels. An impedance measurement module is implemented based on the lock-in amplifier technique to measure the impedance change during antibody growth on the gold electrodes which is caused by trapped proteins in the detection region. The impedance measurement results confirm the presence of trapped proteins. Distinguishable impedance profiles, measured at frequencies in the range of 10-100 kHz, for the detection area taken before and after the presence of proteins validate the performance of the proposed system.