Microfluidic flow cytometry: The role of microfabrication methodologies, performance and functional specification

Abstract

Flow cytometry is an invaluable tool utilized in modern biomedical research and clinical applications requiring high throughput, high resolution particle analysis for cytometric characterization and/or sorting of cells and particles as well as for analyzing results from immunocytometric assays. In recent years, research has focused on developing microfluidic flow cytometers with the motivation of creating smaller, less expensive, simpler, and more autonomous alternatives to conventional flow cytometers. These devices could ideally be highly portable, easy to operate without extensive user training, and utilized for research purposes and/or point-of-care diagnostics especially in limited resource facilities or locations requiring on-site analyses. However, designing a device that fulfills the criteria of high throughput analysis, automation and portability, while not sacrificing performance is not a trivial matter. This review intends to present the current state of the field and provide considerations for further improvement by focusing on the key design components of microfluidic flow cytometers. The recent innovations in particle focusing and detection strategies are detailed and compared. This review outlines performance matrix parameters of flow cytometers that are interdependent with each other, suggesting trade offs in selection based on the requirements of the applications. The ongoing contribution of microfluidics demonstrates that it is a viable technology to advance the current state of flow cytometry and develop automated, easy to operate and cost-effective flow cytometers.

Passive Dielectrophoretic Focusing of Particles and Cells in Ratchet Microchannels

“…Sheath fluids are often used to confine particles into a well-defined volume, which, however, requires an accurate control of flow rates. This is because sheath-flow focusing acts upon the suspending fluid, not the suspended particles [11]. Therefore, a variety of forces, which may be externally imposed (termed as active focusing) or internally induced (termed as passive focusing), has been demonstrated to directly manipulate particles for sheath-free focusing [12].…”

Cell Cytometry: Review and Perspective on Biotechnological Advances

“…The material chosen for electrode fabrication depends on its electrochemical properties and manufacturability. Gold (Au) is commonly used because it is electrochemically stable and biologically inert, but other materials like Silver (Ag), Platinum (Pt), Nickel (Ni), and even liquid electrodes made by inserting Silver/Silver Chloride (Ag/AgCl) wires in conductive electrolyte solution have also been demonstrated (Shrirao et al, 2018). Although several variations of electrode configurations exist, the two most common configurations adopted in microfluidic devices are the co-planar and parallel electrode arrangements.…”

Microfluidic techniques for separation of bacterial cells via taxis

“…Flow cytometry is now quite advanced and allows sorting of tens of thousands of cells per second by as many as 14 parameters [79]. The primary advantage of microfluidics in comparison with cytometry is its portability, with applications to point of care diagnostics, as well as reduced sample volumes and more precise and stable flow control [80]. However, microfluidics and cytometry are not in opposition to each other, and, increasingly, these methods are integrated to develop highly efficient cytometers with diversified functionality in cell sorting, counting, lysis and single cell analyses on a single chip [81].…”