A modern flow cytometer can analyze and sort particles on a one by one basis at rates of 50 000 particles per second. Flow cytometers can also measure as many as 17 channels of fluorescence, several angles of scattered light, and other non-optical parameters such as particle impedance. More specialized flow cytometers can provide even greater analysis power, such as single molecule detection, imaging, and full spectral collection, at reduced rates. These capabilities have made flow cytometers an invaluable tool for numerous applications including cellular immunophenotyping, CD4+ T-cell counting, multiplex microsphere analysis, high-throughput screening, and rare cell analysis and sorting. Many bio-analytical techniques have been influenced by the advent of microfluidics as a component in analytical tools and flow cytometry is no exception. Here we detail the functions and uses of a modern flow cytometer, review the recent and historical contributions of microfluidics and microfabricated devices to field of flow cytometry, examine current application areas, and suggest opportunities for the synergistic application of microfabrication approaches to modern flow cytometry.

The intersection of flow cytometry with microfluidics and microfabrication.

Ferrofluids have many traditional applications in the electrical, mechanical and optical fields, including transformers, dampers, imaging systems, and so on. However, in more recent years, the potential provided by ferrofluids to manipulate tiny quantities of liquid by means of external magnetic fields has attracted great interest in the microfluidics domain; resulting in the emergence of a new branch of scientific known as micro-magnetofluidics. This study reviews recent applications of micro-magnetofluidics techniques to six common microfluidic functions, namely micromixing, pumping, focusing, sorting, droplet formation and transfer phenomena. For each function, the fundamental interaction mechanisms between the ferrofluid and the magnetic field are described and the main experimental and numerical results are discussed.

Micro-magnetofluidics in microfluidic systems: A review

Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned

Miniaturization is being increasingly applied to biological and chemical analysis processes. Lab-on-a-chip systems are direct creation of the advancement in the miniaturization of these processes. They offer a host of exciting applications in several areas including clinical diagnostics, food and environmental analysis, and drug discovery and delivery studies. This paper reviews lab-on-a-chip systems from their components perspective. It provides a categorization of the standard functional components found in lab-on-a-chip devices together with an overview of the latest trends and developments related to lab-on-a-chip technologies and their application in nanobiotechnology. The functional components include: injector, transporter, preparator, mixer, reactor, separator, detector, controller, and power supply. The components are represented by appropriate symbols allowing designers to present their lab-on-a-chip products in a standard manner. Definition and role of each functional component are included and complemented with examples of existing work. Through the approach presented in this paper, it is hoped that modularity and technology transfer in lab-on-a-chip systems can be further facilitated and their application in nanobiotechnology be expanded

Lab-on-a-chip: a component view

In this work, we demonstrate an integrated, single-layer, miniature flow cytometry device that is capable of multi-parametric particle analysis. The device integrates both particle focusing and detection components on-chip, including a “microfluidic drifting” based three-dimensional (3D) hydrodynamic focusing component and a series of optical fibers integrated into the microfluidic architecture to facilitate on-chip detection. With this design, multiple optical signals (i.e., forward scatter, side scatter, and fluorescence) from individual particles can be simultaneously detected. Experimental results indicate that the performance of our flow cytometry chip is comparable to its bulky, expensive desktop counterpart. The integration of on-chip 3D particle focusing with on-chip multi-parametric optical detection in a single-layer, mass-producible microfluidic device presents a major step towards low-cost flow cytometry chips for point-of-care clinical diagnostics.

/pdf/an-integrated-multiparametric-flow-cytometry-chip-using-arihj2nk66.pdf

An integrated, multiparametric flow cytometry chip using "microfluidic drifting" based three-dimensional hydrodynamic focusing.

This study reports an integrated microfluidic system capable of isolation, counting, and sorting of hematopoietic stem cells (HSCs) from cord blood in an automatic format by utilizing a magnetic-bead-based immunoassay. Three functional modules, including cell isolation, cell counting, and cell sorting modules are integrated on a single chip by using microfluidic technology. The cell isolation module is comprised of a four-membrane-type micromixer for binding of target stem cells and magnetic beads, two pneumatic micropumps for sample transport, and an S-shaped channel for isolation of HSCs using a permanent magnet underneath. The counting and sorting of HSCs are performed by utilizing the cell counting and sorting modules. Experimental results show that a separation efficiency as high as 88% for HSCs from cord blood is achieved within 40 min for a sample volume of 100 μl. Therefore, the development of this integrated microfluidic system may be promising for various applications such as stem cell research and cell therapy.

/pdf/an-integrated-microfluidic-system-for-isolation-counting-and-1fnuuclr1w.pdf

An integrated microfluidic system for isolation, counting, and sorting of hematopoietic stem cells

The paper presents a new immunomagnetic-bead-based microfluidic system integrated with an optical detection module for rapid diagnosis of influenza infection. By using the immunomagnetic beads conjugated with influenza-specific antibodies, the developed system can detect influenza viral particles with a high sensitivity and specificity while compared with large-scale systems. The viral particles were firstly recognized and adhered onto the surface of the magnetic beads, then incubated with the developing antibodies labeled with fluorescent dye, and finally detected optically. The developed micro system can perform automatic mixing, transportation and detection of influenza virus within a short period of time and could lead to a crucial platform for biological and medical applications.

An immunomagnetic-bead-based microfluidic system for rapid diagnosis of influenza infection

This study presents a new method for generating tunable and uniform magnetic alginate microbeads, which can be widely employed in the field of the bead-based bioassays such as sample pretreatment or immunoassays. The proposed microfluidic chip comprises pneumatically-driven vibrators to continuously spot alginate microdroplets in a thin oil layer. Continuously, the temporarily formed alginate microdroplets sank into a CaCl 2 solution to become gelled microbeads. Besides, 8 microchannels with radiation-shape arrangement were designed to equally distribute the alginate/magnetic-nanoparticles suspension supplied by only one syringe pump. In addition the sandwiched fluorescent immunoassay (FIA) for the detection of dengue virus can also be carried out by utilizing the magnetic alginate microbeads. Therefore, the tunable and uniform magnetic alginate microbeads can be successfully generated and demonstrated for biological applications.

Ruo-Chi Hsu

Papers

An integrated microfluidic system for isolation, counting, and sorting of hematopoietic stem cells

An immunomagnetic-bead-based microfluidic system for rapid diagnosis of influenza infection

Tunable magnetic alginate microbeads by using a spotting-based alginate microbead generator and Its applications for immunoassay-based diagnosis