The Global Digital PCR landscape in 2023

Article Source: IVD Research SocietyMedical Industry Observation

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Digital PCR has been around for 30 years and there are over 30 related enterprises worldwide. In the past three years, more than 300 articles on digital PCR have been written on various platforms. It can be roughly divided into three categories: First, pure technology, which covers the formulas, charts, curves of digital PCR, as well as product analysis, etc. Generally, the authors are technical R&D personnel. Two: Pure Market, covering the history, development pattern, company introduction and market share of digital PCR. Generally, the author is a market, media or industry analyst. Three: Pure application, discussing the clinical and research applications of digital PCR, usually authored by marketers or doctors.

Technology, market and application respectively correspond to the three stages before, during and after the product cycle. Naturally, three styles of articles also emerged. Engineer Huang wants to integrate the three and write something different. There are so many articles about digital PCR. How can I write something new? To be honest, it's quite difficult. Fundamentally, it lies in having differentiated innovative thinking on the premise of respecting the origin of things.

This article focuses on addressing several key issues: First, what is digital PCR, its development history, and what systems does it consist of? Second, globally, which manufacturers are engaged in the research and development of digital PCR, how are they developing, and what is their temporal and spatial distribution? Three, what are the global digital PCR technology routes, product iterations, and technical parameters like? Four, what is the capital activity status and market share change trend in the digital PCR sector? Five, what are the backgrounds and experiences of the leading figures in digital PCR?

The concept and system of digital PCR

What is digital PCR? Mr. Huang's understanding is: The third-generation PCR, microfluidics + real-time fluorescent PCR. Moreover, since the final detection is based on the reading of negative/positive signals, namely 0 and 1, which are digital signals recognizable by the computer, it is an absolute quantitative DNA detection method that can accurately count. From this perspective, it can also be understood as digital PCR. (The above is a common explanation.

In professional terms, digital PCR divides DNA or cDNA samples into many individual, parallel PCR reactions. Each reaction well serves as an independent reactor, containing or not containing one or more copies of the target molecule (DNA template), thereby achieving "single-molecule template PCR amplification". By conducting statistical analysis on the number and proportion of negative and positive signals presented, the template copy number in the original sample is calculated to achieve precise quantification.

In 2006, the first commercial digital PCR system, Biomark HD, was officially released. It has been nearly 20 years since then. The first-generation PCR system was put into commercial use in 1987. The second-generation PCR system was put into commercial use in 1996. The third-generation PCR was commercially launched in 2006. That is to say, it is iterated on average once every ten years. The launch of commercial use refers to the fact that the PCR system has solved key technical and process issues and begun large-scale sales. The invention (concept proposal) of the technology, however, occurred several years earlier. The technological inventions of the first to third generations of PCR were in 1983, 1992 and 1999 respectively. It took 4 to 7 years from the birth to the industrialization of PCR technology.

The digital PCR reaction process generally includes: sample preparation, droplet preparation, PCR amplification, and fluorescence signal detection and analysis. From the perspective of the reaction process, the system composition of digital PCR consists of three core components: the liquid path system, the temperature control system, and the optical path system. The liquid path system mainly addresses the issue of microdroplet preparation. There are generally several methods, including oil-liquid/gas-liquid heterogeneous separation, regular vibration separation, and microfluidic physical separation. The temperature control system mainly addresses the issue of heating and cooling in PCR reactions. The optical path system mainly addresses issues such as light source excitation, optical signal collection, conversion, and analysis.

The technical route is mainly classified from the perspective of the form of microdroplet preparation. At present, there are mainly two directions. Firstly, droplet digital PCR (ddPCR) essentially separates liquid samples with an oil phase, regardless of the tools, carriers, materials, forms, or actions used. Secondly, chip digital PCR (cdPCR) essentially involves directly aliquot and inject the sample to be tested and reagents into a formed, fixed-volume chip chamber to create individual droplets. Both of these routes have their advantages and disadvantages. Ultimately, it still depends on the user's choice, which will be proven by time.

A digital PCR system is not just one device. Before the advent of the digital PCR all-in-one machine, the entire system was composed of 3 to 4 devices. It generally includes: droplet preparation instrument, PCR cyclic amplification instrument, microplate sealing instrument, droplet reader (biochip analysis/reading instrument), etc. Since the first digital PCR was commercially launched in 2006, no less than 37 products have been released both at home and abroad over the past 17 years.

Digital PCR technology originated in the United States and finally spread in Europe and America. In recent years, especially in China, it has received significant development and promotion. This is driven by policy-level factors, capital, and the demands of scientific research and clinical clients, which also account for a portion. From the perspective of the global digital PCR market, North America remains the largest dominant market for digital PCR, followed by Asia and Europe. Growth in Africa and South America is sluggish. According to a survey by the renowned institution Allied Market Research, the global digital PCR market was valued at 508.82 million US dollars in 2020 and is projected to reach 1.3053 billion US dollars by 2030, growing at a compound annual growth rate of 8.6% from 2021 to 2030.