Microarray biochip

In early 2015, then-US President Barack Obama announced the launch of a new large-scale research and development project, “Precision Medicine Initiative”, in his State of the Union Address, and declared that the United States is entering the era of precision medical care. Since then, the slogan of precision medicine has been widely accepted, and human medicine has entered a new era. Biochip testing is an important pioneer in precision medicine and preventive medicine.

According to the definition on Wikipedia: A biochip is a high-tech element made of substrates such as silicon wafers, glass, or polymers by using micro-electromechanical system (MEMS)-based automation or other precision fabrication technologies and is designed based on the principles of molecular biology, genetic information, and analytical chemistry; it is capable of performing fast and complicated operations, similar to semiconductor chips. Biochips have fast, accurate, and low-cost bioanalytical testing capabilities. In molecular biology, biochips are basically miniaturized laboratories that can perform hundreds or thousands of biochemical reactions simultaneously. Biochips allow researchers to quickly screen large numbers of biological analyses for a variety of purposes, from disease diagnosis to bioterrorism detection.

The biochips currently under development can be roughly divided into two types: microarray and lab-on-a-chip. DNA microarray chip is an area of rapid development among all types of biochips. DNA microarray chip refers to the installation of thousands or tens of thousands of nucleic acid probes over a few square centimeters, providing a large number of gene sequence-related information through a single test.

Blood glucose monitoring chips are currently the most popular biochips. The level of blood glucose is measured as a reference for monitoring the intake of sugary foods and the amount of injected insulin. The blood glucose monitoring chip measures the glucose level in the blood at a single moment in time and is a low-density chip. However, samples are not easy to obtain in real life or through scientific research. Scientists and engineers have tried to obtain more information quickly and accurately and thus people have tried to construct different probes of the same reaction conditions at different sample points on the same chip. Each sample point is made of thousands of identical probe bundles, thus forming a microarray biochip for rapid, multiplexed, and efficient biometric detection.

The material of the sample points of a microarray biochip may be a probe bundle made of DNA, RNA, peptide proteins, antibodies, cells, or human tissues. The design of the sample point material is entirely dependent on the biometrics to be measured. For example, a single nucleotide polymorphism (SNP) used to detect the change of a single nucleotide A, T, C or G in a gene sequence consists of sample points made of fragments of different single-stranded DNA sequences based on the principles of AT- and GC-base pairs in DNA. A DNA sequence with a single nucleotide change can be detected when the designed sample point of a single-stranded DNA is paired with the sample and emits fluorescence. The change of the DNA sequence can be used to study genetic diversity between species (including humans). Another example is protein biochips for detecting food-specific allergens. Typically, sample points consisting of tens to hundreds of different food allergens are placed on a standard 1″ x 3″ glass chip with a size of 200~500 microns. Through the probe design of the sample point and the intensity of the fluorescent signal, it is possible to perform screening tests of tens to hundreds of different food allergens at the same time.

In order to correctly read the position of each sample point and the intensity of the fluorescent signal of the reaction of a microarray biochip and thus correctly interpret various biometric signals, it is necessary to have a precise and fast scanner capable of measuring different fluorescent signals of the sample points of a microarray biochip to avoid misinterpretation, especially to completely avoid false positives. In addition to accurate interpretation, the requirements for the use of microarray biochip scanners also include: (1) High optical resolution: The higher the optical resolution of the scanner, the more accurate the measured value and the smaller the size of the biological sample point. Likewise, the smaller the biochip with the same density at the detection point, the less sample required and the faster the reaction. (2) High integration: In addition to the functional requirements of the hardware, it is necessary to have image software for accurate analysis and a software interface that is easy for the customer to operate. (3) High cost effectiveness: At present, the price of commercial machines varies depending on the function. Generally, the price per unit is NT$1.5 million, though some may cost as much as NT$4–5 million. The machine cannot be widely used, because it is too expensive. It is believed that the popularity of biochips and machines will be greatly improved if the price can be reduced to NT$1 million or even as low as NT$300,000–400,000 per unit.

 


Figure 1 Principles of detection and application of microarray biochips

In terms of application services, population aging in developing and developed countries has increased significantly, and with the increase in health care and environmental awareness, the demands for easy, energy-saving and low-cost health care expenses, such as detection of cancer, various diseases and allergens, effectiveness of medication, and agricultural genetic testing/diagnostics, will increase accordingly.

In addition, there are 20 million pregnant mothers in Mainland China every year, meaning that chromosome (DNA) microarray will be increasingly popular for examining chromosomal abnormalities in fetuses. Based on an estimate of 10% market share, Mainland China will use 2 million chromosomal microarrays per year. Currently, the cost of testing for each chromosomal microarray is RMB 2,400. Therefore, it is estimated that the annual test fees for fetal chromosomal microarray will be as high as RMB 4.8 billion. At present, there are 5,800 level-2A hospitals in China. If 30% of these hospitals use microarray biochip scanners for chromosomal microarray testing of fetuses, that would be equivalent to 1,700 hospitals, and if each hospital buys 3 to 5 scanners for different departments, then the estimated total demand for scanners in mainland China will reach 6,000 units. Since the application of microarray biochips and scanners is now only an emerging demand in Mainland China, it is estimated that there will be great room for future growth in the Chinese and global markets, and growth is expected.

Caduceus Biotechnology Inc.:http://www.caduceus.com.tw/