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Application of LoC and LoPCB technology in the diagnosis of COVID-19

Today I will talk about some applications of Lopcb technology in the epidemic.
After the outbreak of the new virus, epidemiological and clinical investigations must be carried out as soon as possible, and the emergence of COVID-19 has prompted people to urgently need to understand the transmission mode, severity, clinical symptoms and risk factors of this virus. Effective tests can not only confirm whether the human body is infected with the virus, but also indicate the geographic location, extent, and transmission of the disease outbreak.

A number of methods for detecting and diagnosing COVID-19 are in the development stage, some of which can specifically detect this new virus; while others can detect genetically similar virus strains. A recently developed test kit uses a technology based on a portable lab-on-chip (LoC) platform, which can detect, identify and distinguish MERS-CoV, SARS-CoV and COVID-2019 in one test. For viruses, this kit integrates two molecular biology applications: polymerase chain reaction (PCR) and DNA microarray screening. Traditional PCR coronavirus detection kits take a day to get test results, while the latest LoC test kits only need 2 hours to get results, and LoC technology may be the result of the development of powerful new diagnostic instruments and real-time test equipment. The essential.

LoC is a device that integrates one or more laboratory functions on a single integrated circuit. LoC equipment is a kind of micro-electromechanical system (MEMS) equipment, which plays the role of "micro total analysis systems" (micro total analysis systems, referred to as µTAS). Generally speaking, it uses the principle of microfluidic control to control trace amounts of liquid. In fact, microfluidics is a technique for conducting small-scale chemical experiments to imitate the natural state. Biomedical microelectromechanical systems (BioMEMS) has developed into a branch of MEMS devices, used in biomedical research and medical micro-devices, focusing on mechanical components and micro-manufacturing technology. Specific applications include disease detection, chemical monitoring, and drug delivery. The market for BioMEMS technology is developing very fast. Many BioMEMS devices are already on the market. The most familiar one is the blood glucose sensor. LoC technology based on microfluidics also has great potential for large-scale commercialization.

LoC is not a new technology. In fact, as early as the late 1990s, with the development of micro-manufacturing technology, the industry has developed a fully automated LoC for integrated sample preparation, fluid manipulation, and biochemical analysis. Methods derived from semiconductor manufacturing technology can transform experimental and analytical protocols into a chip structure containing interconnected reservoirs and paths (Figure 2). Using electromotive force or pressure to control fluid flow through the selected path is equivalent to creating valves and pumps that can complete operations, including distribution, mixing, incubation, reaction, sample division and detection.
The first commercially available LoC product on the market came out in 1999. It is used to analyze DNA and RNA biomolecule, protein and cell assays, and more than 7,000 units have been sold worldwide. This LoC bioanalyzer uses sample reagents and chips to process nucleic acids, proteins, and cells on the same platform, and sets the industry standard for RNA analysis and sequencing. The LoC technology that integrates chemical analysis and biochemical analysis has developed rapidly in the past decade. Although this technology is mainly used for medical treatment, its basic technology is suitable for various analysis functions and monitoring functions, and logically conforms to the concept of "Unicom World"

A variety of materials can be used to manufacture microfluidic devices-including glass, rigid polymers and elastomers. The available technologies include CNC milling, injection molding, and photolithography. Available raw materials are silicon, because the manufacturing technology is derived from semiconductor manufacturing, and due to the requirements for specific material properties, reducing production costs and speeding up sample manufacturing, a variety of alternative processes have now been developed. The industry has shown more and more complex chips, but due to the lack of mature commercial manufacturing technology, only a few of them can be marketed. 3D printing technology has recently become an alternative method of manufacturing fluid equipment, and may replace soft micro-etching technology and become the preferred method for rapid sample manufacturing. However, the existing technology is not unified, and it is still uncertain which process and material will eventually be used for a large number of diagnoses.

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The basic components of LoC

The components of LoC are (Figure 3):
1. Electrophoresis: separation column
2. Microfluidics: channels, valves-pumps and mixers
3. Biochemical detectors and sensors
4. Microfluidic chip

1. Electrophoresis

Under the action of an electric field, a mixture of similar molecules flows to a liquid electrode (anode or cathode) on different media (such as paper, glass, gel, liquid) to separate large molecules (that is, DNA fragments, blood or other proteins). This method has been used to separate and purify biomolecules. Each molecule flows through the medium at a different speed, depending on the charge and its size, and finally flows to the anode or cathode at a unique speed

Figure 4: LoC analysis sequence using electrophoresis in microfluidics

2. Microfluidics
The customized application of fluid technology is combined with traditional precision processing technology, such as wet etching, dry etching, deep reactive ion etching, sputtering, anode bonding and fusion bonding, etc., to manufacture fluid dynamic channels and fluid sensors for various LoCs , Chemical detectors, separation capillaries, mixers, filters, pumps and valves (Figure 4).

The flow in the microchannel is laminar, which can selectively process the cells in the microchannel, array or biochemical reaction. Integrate microelectronics, micromechanics, and microoptical technologies on the same substrate to realize automatic equipment control, reducing human error and operating costs.

3. Biochemical detectors and sensors
The detectors, sensors and electrodes can be ChemFET and BioFET C-MOS devices with special membranes or diffusions to make them sensitive to chemical or biological molecules. Sensors and electrodes are electrical components sensitive to various chemical molecules or biomolecules, and are electroplated with gold, silver, platinum or palladium, etc. and corresponding metal salts

4. Microfluidic chip
Microfluidic chips are a set of microchannels etched or molded on materials (glass, silicon, or polymers like PDMS) to achieve the required functions (mixing, pumping, classification, control of the biochemical environment, etc.) ). The network (the interface between the micro world and the macro world) formed by the micro channel (the interface between the micro world and the macro world) is connected to the outside through the input (inlet) and output (outlet) pierced on the chip.

LoC material

In the past few years, the industry has developed a variety of LoC materials. The earliest material was silicon in the late 1990s. The microelectronics industry developed various methods of precision machining of silicon (MEMS) for the manufacture of accelerometers for airbag sensors. Subsequently, materials developed from silicon wafers to glass and later polymers. Recently, the use of PCB and various paper materials is more popular.

When manufacturing LoC, the use of silicon and glass has many advantages, but the cost is also the highest. Polymers—especially PCBs—have become a new choice because various materials can be found in the market and the integration of electronic products and various printing technologies can be achieved.