Digital PCR in the Integrated Era: Unlocking the Door to Clinical Diagnostics

Domestic DigitalPCRThe sector is still warming up.

Previously, Sinaford Medical, a domestic digital PCR company, announced the completion of its Series B financing round of nearly RMB 200 million, setting a new record for the largest single financing transaction in this sector.

On one hand, international giants in molecular diagnostics are making significant moves in the digital PCR (dPCR) arena. Recently, following the launch of its flagship all-in-one dPCR system, the QX One, Bio-Rad introduced a multi-channel version, the QX600. Qiagen launched three all-in-one dPCR instruments at once through mergers and acquisitions, while Stilla Technologies, under Illumina, released a new six-channel detection product. As a long-established dPCR supplier, Thermo Fisher Scientific, facing limited competitiveness with its QuantStudio 3D platform, rapidly integrated a new platform and quietly listed the QuantStudio™ Absolute Q™, marking a strong comeback. Although not yet officially disclosed, Roche, another molecular diagnostics giant, is warming up for the release of its dPCR products; it is reported that demo units are already visible in China. Thus, nearly all major international molecular diagnostics companies have established their presence in the dPCR sector. Meanwhile, it is evident that the high-end competitive landscape of digital PCR has officially entered the “all-in-one era.”

On the other hand, top-tier investment firms have made significant bets. High-quality digital PCR companies such as Sinaford Medical, New羿 Biotech, Ruixun Biotech, and Linghang Gene have successively completed new rounds of financing. Following New羿 Biotech’s securing of RMB 150 million in early this year—the highest financing amount in the sector—Sinaford Medical further raised the bar for domestic digital PCR financing to nearly RMB 200 million. Among the investors entering the digital PCR space during this wave, many prominent domestic and international institutions are notable participants.

As next-generation sequencing (NGS) becomes increasingly saturated and the supply and demand for real-time quantitative PCR (qPCR) approach equilibrium, the stage once occupied by digital PCR appears to be reopening.

In the rapidly iterating landscape of medical device innovation, few new technologies manage to achieve a second wind, yet digital PCR has done just that. In fact, behind the resurgence of this sector lies a shifted growth logic for the digital PCR industry.

First, the repeated nationwide nucleic acid testing during the COVID-19 pandemic helped rapidly and efficiently educate the market on molecular diagnostics, while also demonstrating the rigid demand for highly sensitive nucleic acid testing. Although it was the previous-generation qPCR that truly gained prominence as a result, the cognitive barrier to the adoption of digital PCR products has been significantly lowered. Second, as mentioned at the beginning of this article, diagnostic instrument giants such as Bio-Rad, Qiagen, Roche, Thermo Fisher Scientific, and Illumina have all made strategic moves in this field. In particular, Qiagen, a dominant player in qPCR, has shifted its focus to make significant breakthroughs in digital PCR, giving people further reason to consider the future potential of digital PCR.

Among these factors, the fundamental rationale behind the digital PCR industry lies in its significant technological advantages over qPCR, particularly in terms of signal-to-noise ratio, accuracy, and reliability.

Industry practitioners told VCBeat that, from a purely technical perspective, the emergence of digital PCR (dPCR) represents a revolutionary breakthrough in the field of PCR, achieving significant improvements in many aspects. Specifically, dPCR employs a reaction system with molecular-level partitioning, which reduces competitive inhibition between molecules, effectively increasing the signal-to-noise ratio of samples by 3–4 orders of magnitude. Meanwhile, the quantification method used in dPCR has shifted from the “comparative quantification” approach based on reference standards to a “counting quantification” method grounded in statistical models, greatly enhancing quantitative accuracy. Furthermore, signal readout in dPCR has been upgraded from the analog signal detection used in quantitative PCR (qPCR) to digital signal detection, improving the anti-interference capability of the detection system and substantially lowering the performance requirements for reagents throughout the testing process. For dPCR, test results no longer depend on the amplification efficiency of the reaction system, which significantly optimizes the reliability of detection outcomes, particularly when analyzing complex samples.

In other words, once digital PCR products reach a level of maturity in terms of cost and ease of use that rivals qPCR, it will mean there is hope for rapidly replacing the latter in existing scenarios.

“From the perspective of clinical needs, molecular diagnostics can be broadly divided into two categories,” a product manager with years of experience in promoting digital PCR applications told VCBeat. “One category is multi-locus qualitative testing, which is primarily used in screening and mainly employs technical platforms such as NGS and gene chips; the other is few-locus quantitative testing, generally used in companion diagnostics.” In multi-locus screening tests, PCR technology does not offer significant advantages except in scenarios requiring extremely high sensitivity (e.g., liquid biopsy and microbial detection in body fluids). However, once a diagnosis is confirmed and treatment begins, or when specific few loci need to be tested, PCR technology becomes almost the only viable solution. This is because, for the detection of a few known genetic loci, PCR technology offers better cost-effectiveness in terms of both qualitative sensitivity and quantitative accuracy. “Currently, although qPCR remains the mainstream technical platform in the PCR market, digital PCR will undoubtedly see huge market opportunities once its technological maturity and cost optimization reach sufficient levels,” said the product manager.

Moreover, for developers and end-users of digital PCR (dPCR), the deeper reason behind this resurgence lies in the substantial breakthroughs achieved in dPCR product forms, driven by accumulated technological and process expertise. The transition from multi-tool combinations to integrated workflows, from outsourcing samples to localized testing, and from complex operations to user-friendly interfaces has gradually turned the vision of dPCR superseding quantitative PCR (qPCR) into reality.

Digital PCR technology has a development history of over 20 years. However, from a product perspective, digital PCR is still in its early stages, with most digital PCR products remaining at the stage of “combinations of multiple tools.” In other words, if mapped onto the development trajectory of qPCR, the maturity level of most current digital PCR products corresponds to the semi-automated stage of two decades ago—characterized by complex operations and limited accuracy.

A significant reason for the lag in productization is the considerable technical difficulty in achieving integration using traditional microfluidic solutions. This is because droplet generation, amplification, and detection each require different consumables and invoke distinct functional modules of the equipment, thereby greatly increasing technical complexity. It is reported that Bio-Rad, as one of the earliest pioneers in digital PCR products, took nearly a decade to complete the product iteration of its digital PCR instruments from multi-tool systems to integrated platforms, while many other digital PCR manufacturers have gradually exited the market after repeated failed attempts.

Even though Bole Company has finally launched the Qxone, it only achieves an integrated product form based on internally integrated robotic arms. However, digital PCR operations involve numerous modules and components, making it difficult to ensure the stability and maintainability of the integrated system from a process perspective, with relatively high costs as well. In China, although many digital PCR R&D teams have been continuously attempting, there is still no digital PCR all-in-one machine with microfluidic solutions available on the market.

The form factor of digital PCR products has long remained stagnant, severely limiting the technology’s potential and resulting in the persistent inability of these products to enter the IVD sector.

An industry practitioner revealed to VCBeat that, due to the immaturity of products, digital PCR (dPCR) only began to gradually enter the clinical market in 2020. Prior to this, its applications were mainly confined to scientific research and public health, with fewer than 1,000 units installed across China. “At present, foreign brands are the primary players capable of effective implementation. Among them, Bio-Rad has deployed 500–600 units nationwide, adding 100–150 units annually. Stilla follows, with a cumulative installation base of 60–80 units and an annual increase of approximately 20–30 units. Qiagen has also gradually gained a foothold over the past year after shifting its strategic focus to digital PCR,” the practitioner pointed out. “In China, the model is dominated by reagent rental with test kits provided free of charge. While the growth rate of installations is relatively fast, the number of actively used units remains insufficient. Overall, market penetration is still in its early stages. Given the current installation base of quantitative PCR (qPCR), there is immense potential for future growth.”

Therefore, for digital PCR manufacturers, technological optimization and product iteration remain top priorities. Only by addressing issues related to product form factors and enabling the gradual penetration of digital PCR into diverse application scenarios can its advantages—high sensitivity and accurate quantification—be fully realized, thereby progressively replacing qPCR technology.

In a sense, 2020 marked the beginning of the “integrated era” for digital PCR and its inaugural year of clinical implementation.

In early 2020, Bio-Rad launched the QX One™, the world’s first all-in-one digital PCR system, marking a significant milestone in the industrialization of digital PCR. This launch signaled that digital PCR products had entered an integrated phase, with their maturity level essentially reaching that of quantitative PCR (qPCR), thereby creating a breakthrough for the expansion of this technology from scientific research and public health into clinical diagnostics. A few months later, Qiagen prominently unveiled its QIAcuity™ series of all-in-one digital PCR systems.

VCBeat has noted that as industry giants Bio-Rad and Qiagen compete to launch integrated digital PCR instruments, the Chinese digital PCR company Sinaford Medical has also introduced its all-in-one digital PCR system, the DQ-24. Reportedly independently developed by Sinaford Medical, the DQ-24 offers a user experience closely resembling that of ABI’s classic 7500 qPCR instrument. As the first domestically produced integrated digital PCR instrument and the third such product globally to reach the market, the launch of the DQ-24 signifies that China’s digital PCR technology has reached a world-leading level, demonstrating parity with top international players in terms of product maturity.

According to Sheng Guangji, founder of Sinaford Medical, Sinaford’s digital PCR technology has not only surpassed existing products in performance but also completely broken away from the traditional path of “import imitation and domestic substitution.” Starting with fundamental technological innovation, Sinaford Medical has pioneered a novel “vibrating injection” technical route, established its own proprietary technology system, and implemented a comprehensive international patent layout. Based on the “vibrating injection” technology, the DQ-24 integrates droplet generation, amplification, and detection into a single location, thereby avoiding complex droplet transfer issues. Furthermore, the volume and number of droplets can be adjusted according to experimental requirements.

“The DQ-24 boasts the highest level of automation among comparable products currently available,” pointed out Sheng Guangji. “It requires minimal manual intervention from users; simply loading the eight-tube strip is sufficient. The operational experience is nearly identical to that of qPCR, resulting in virtually zero learning curve.” Furthermore, the oil phase used for droplet generation is mineral oil, which offers the advantages of low cost, non-volatility, and environmental friendliness. The DQ-24 is also the only digital PCR platform on the market capable of seamless compatibility with existing qPCR reagent systems. Users can directly adopt experimental protocols already optimized for qPCR platforms, eliminating the need for redundant development and significantly reducing the workload associated with platform upgrades. Additionally, as the DQ-24 does not require microfluidic consumables, the cost per test is reduced by an order of magnitude compared to similar products, holding promise for driving the large-scale adoption and implementation of digital PCR technology in clinical settings.

Currently, the DQ-24 has been launched on the market and is rapidly scaling up. “It can now be said that we are in the best era for the commercialization of integrated digital PCR instruments. The concept of digital PCR slowly permeated various application scenarios over many years, followed by continuous product iterations by international giants, which significantly reduced the market education costs required to promote user adoption of digital PCR instruments,” said Sheng Guangji. “Meanwhile, the lower installation costs and more timely technical support offered by domestically produced equipment have become competitive advantages in rapidly capturing market share. Within less than a year, we have achieved cumulative installations of nearly 100 units. The market penetration rate of integrated digital PCR is far faster than in the past, fully demonstrating users’ enthusiasm for this technology.”

Therefore, as digital PCR, a molecular diagnostic technology with superior performance, finds its appropriate and mature product form, it seems only a matter of time before it opens the door to the clinical testing market. Imagine, under the same usage costs and with a better operational experience, what reason is there to reject nucleic acid detection technology with higher sensitivity and precision?

The current craze is that digital PCR is making a comeback and also surpassing expectations.