Microfluidics - BiopharmaDirect

Microfluidics

Microfluidics refers to the science and technology that use micropipes (tens to hundreds of microns in size) to process or manipulate tiny fluids. It involves multiple disciplines such as chemistry, fluid physics, microelectronics, new materials, biology and biomedical engineering. It can integrate the process of analyzing samples in the fields of biology, chemistry, medicine, including preparation, reaction, separation, and detection, into a micron-scale chip, and automatically complete the entire analysis process. Because of its features such as miniaturization and integration, microfluidic devices are usually called microfluidic chips, also called Lab on a Chip or micro-Total Analytical System.

1. The Evolutional History of Microfluidics

Microfluidics is developed accompanied by micro-electromechanical processing system (MEMS) technology. MEMS technology refers to the use of semiconductor technology to miniaturize real-life mechanical systems to form micro-electronic mechanical systems. Based on the characteristics of MEMS technology, microfluidics microfilms a large laboratory system on a glass or plastic substrate to replicate the entire process of complex biological and chemical reactions and complete experiments quickly and automatically. It is characterized by constructing fluid-containing channels, reaction chambers and other functional components on a micrometer scale, and manipulating the movement of micrometer-sized fluids in tiny spaces, thereby building a complete chemical or biological laboratory.

In the 1990s, Manz and Widmer et al. used chips to achieve electrophoretic separation which was previously completed in capillary tubes, and first proposed the concept of Miniaturized Total Analysis System (μTAS) in 1990. After that, micropumps and flow sensors were used. It has been developed one after another, and the emergence of the concept of fluid handling based on integrating a complete laboratory analysis system on a chip has spawned the research of microfluidic chips worldwide.

Figure 1 The birth and evolution of microfluidic technology

2. Advantages and Application Scenarios of Microfluidic Chips

(1) Technical advantages

Microfluidic chip technology based on MEMS development is known as one of the seven technologies that will change the future. Compared with traditional methods, this technology has the following advantages:

Microfluidic technology can concentrate the entire process of sample detection on a chip of a few centimeters. Through the integration of modules such as the design of the liquid flow channel, the placement of the micro valve, and the design of the liquid cavity, the detection operation process is comprehensively completed, and finally the entire detection is miniaturized.

The microfluidic chip can be designed in the form of multi-channels. The sample to be tested can be divided into multiple reaction units through the micro-channel network. Since the reaction units are isolated from each other, multiple tests for a single sample can be performed at the same time if needed. Compared with conventional practice, the detection time is significantly shortened and the detection efficiency is improved as well.

The sample volume required for detection on a microfluidic chip is much smaller, often only at the level of microliters or even nanoscale. At the same time, due to its high-throughput characteristics, multiple tests can be performed on samples collected at one time, so it has more advantages for the detection of samples which are not easy to obtain.

Due to the miniaturization characteristics of the microfluidic chip, the internal reaction unit cavity is also very small, making the total volume of the entire reaction system very small, and greatly reducing the consumption of reagents compared with the traditional detection system.

(2) Application scenarios

Owing to the above-mentioned advantages, microfluidic chips enjoys very broad application prospects in different fields. For example, in the field of in vitro diagnostics, microfluidic chips can be applied in a range of IVD subdivisions such as biochemical analysis, immunodiagnosis, and molecular diagnosis, and has great potential to replace traditional IVD detection methods. In addition, the advantages in cell separation can greatly improve the detection rate and purity of circulating tumor cells, thereby providing key support for the treatment of related cancers. In the field of drug screening, stem cell chips can overcome the limitations of existing stem cells for in vitro research, by accurately controlling various factors in the stem cell microenvironment in real time, and simulating the complex environment of stem cell growth and differentiation as much as possible.

Figure 2 Application scenario of microfluidic chips

3. Introduction to Microfluidic Technology

(1) Materials for microfluidic chips: silicon wafers, glass, PDMS, paper, etc.

Figure 3 Microfluidic chips of different materials

(2) Microfluidic chip manufacturing technology

The technology used to manufacture microfluidic chips can be roughly divided into the following types:

Figure 4 Microfluidic chip manufacturing technology

(3) Fluid Control in Microfluidic Devices

Microfluidics are divided into passive microfluidics and active microfluidics. Passive microfluidic control, without the help of external force, completes various reactions through the capillary action of the liquid itself. Active microfluidic control precisely controls the reaction chamber in the chip combined with the valve device inside the instrument to precisely control the flow form of the liquid, quantitatively control the volume of the reaction sample, and allow the sample to participate in the reaction to achieve precise control.

Figure 5 Classification of microfluidic chip fluid control methods

4. Microfluidics Market Size, Prospects & Trends

According to the latest statistics from Yole analysts, the global microfluidic product market reached USD 8.7 billion in 2018, and the compound annual growth rate (CAGR) from 2019 to 2024 is as high as 11.7%. It is expected to reach 17.4 billion U.S. dollars in 2024. The two main applications are: (1) point-of-care testing (POCT); (2) pharmaceutical/life science research (including sequencing, genomics and proteomics). Meanwhile, microfluidic are also applying in other areas.

Figure 6 The scale and growth rate of the global microfluidic market (source: Yole)

5. Major manufacturers of Microfluidic Devices

Cepheid

Established in California, USA in March 1963, Cepheid's goal is to solve various difficulties in the process of molecular diagnosis using conventional PCR analyzers. Among all the molecular diagnostic equipment in American hospitals, its dominant product GeneXpert® PCR analyzer based on microfluidic technology accounts for nearly 25% of the total.

BioMérieux

The Film Array, a multiplex PCR analyzer based on microfluidic technology of BioMerieux molecular biology affiliate BioFire, contributed 80% of its income in 2018.

Atlas Genetics (Binx Health)

Founded by Dr. John Clarkson of the United Kingdom in July 2005, Atlas Genetics is a British company focused on POCT molecular diagnostics. Its rapid molecular diagnostic IO system has obtained the European CE certification of in vitro diagnostic products in 2016. Atlas Genetics announces company rebranding, changes name to Binx Health in 2018.

Abaxis

Founded in 1989 and headquartered in California, USA, Abaxis's Vet Scan product portfolio includes chemical and hematology diagnostic instruments and supporting kits. Its Piccolo Xpress®, the only portable diagnostic analyzer to offer a full complement of CLIA-Waived blood chemistry tests at the point of care, has been recognized by the industry as a low-cost, easy-to-operate and quick-resulting microfluidic automatic biochemical analyzer.

Summary

Due to the huge market demand and the irreplaceability of the technology in certain major areas, chances are microfluidic chips will be deeply industrialized in the future. Furthermore, the new economy represented by biomedicine is likely to use microfluidic chips to realize the transformation and upgrading of the current industry, which will have a profound impact on the entire economy.