The Future is Here: Rendu Bio Launches Fully Automated Molecular Diagnostics Workflow

With the full implementation of China’s “universal two-child” policy, increasing attention has been paid to female fertility issues. In recent years, the prevalence of infertility in China has shown a year-on-year upward trend. According to survey results released by the China Population Association, patients with infertility currently account for 12.5% of the population of childbearing age. Among these cases, 20%–60% are caused by reproductive tract pathogen infections. Such infections are closely associated with infertility and can lead to adverse pregnancy outcomes, including preterm birth and miscarriage.

Common pathogens of the reproductive tract include Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Ureaplasma urealyticum (UU), and Mycoplasma genitalium (MG). Chlamydia trachomatis (CT) infection is one of the most common sexually transmitted diseases and a causative agent of pelvic inflammatory disease and cervicitis, which can subsequently lead to tubal infertility, ectopic pregnancy, and chronic pelvic pain. The most common manifestations of Neisseria gonorrhoeae (NG) infection are cervicitis and urethritis; delayed treatment may result in hematogenous disseminated infection. Ureaplasma urealyticum (UU) can also cause urogenital infections. Mycoplasma genitalium (MG) poses hazards similar to those of CT, causing non-gonococcal urethritis and prostatitis in men, significantly impairing sperm quality and leading to male infertility. In women, MG causes cervicitis, and long-term infection can cause irreversible, permanent damage to the fallopian tubes, resulting in tubal infertility. MG infection in pregnant women can lead to severe consequences such as preterm birth, miscarriage, and low birth weight infants.

CT/NG/UU/MG infections are characterized by their insidious nature; studies show that 70% of patients with CT infection and 60% of those with NG infection are asymptomatic. Therefore, early and precise detection of CT/NG/UU/MG infections is of significant clinical importance.

Currently, the conventional method for detecting genital tract microbes in China is immunodiagnosis, which primarily determines the presence of infection by detecting microbial antigens in secretions. Immunodiagnosis is an indirect method of microbial detection that relies on the human immune response to microbial invasion, with a detection rate for Chlamydia trachomatis (CT) infection slightly above 50%. The U.S. Centers for Disease Control and Prevention (CDC) and the International Union against Sexually Transmitted Infections (IUSTI) in the European Union have stated that “among current CT/NG detection methods, molecular diagnostics (NAAT) offer the highest sensitivity and are the preferred testing method.”

It is estimated that the use of molecular diagnostics can increase the detection rate of CT/NG/UU infections to over 95%, significantly reducing the rate of missed diagnoses. In contrast, due to the difficulties in isolation and culture, there were previously no clinical testing methods available for Mycoplasma genitalium (MG). It was not until 2013, when the World Health Organization’s guidelines for the diagnosis of sexually transmitted infections listed nucleic acid amplification tests (NAATs) as the sole diagnostic method for MG, that MG entered the era of precise testing.

Molecular diagnostics was proposed in 1978 by the Chinese-American medical scientist Yuet Wai Kan. Following the invention of PCR technology, molecular diagnostics experienced rapid development. To date, it has become the fastest-growing method in medical laboratory testing.

Molecular diagnostic techniques involve cumbersome operational procedures and present high technical barriers, classifying them as high-end medical testing applications with extremely limited scale. Furthermore, regulatory requirements for molecular diagnostics are exceedingly stringent. As of press time, only slightly more than 3,000 hospitals in China are authorized to employ molecular diagnostics for medical testing, covering less than one-tenth of hospitals nationwide. Dr. Ju Jinliang believes that the widespread adoption of molecular diagnostics must be predicated on full-process automation. However, due to biochemical constraints, microbial DNA is difficult to utilize as a marker for automated molecular diagnostics. In contrast, using microbial RNA as a marker can achieve automation while simultaneously enhancing detection sensitivity.

Dr. Ju Jinliang has been engaged in clinical microbiology research for many years and possesses extensive practical experience in RNA detection. In 2007, Dr. Ju returned to China to establish Rendu Biotechnology, developing and promoting second-generation molecular diagnostic products based on Simultaneous Amplification and Testing (SAT) technology. Headquartered in the Shanghai Zhangjiang Medical Device Park, Rendu Biotechnology holds full independent intellectual property rights for SAT technology. As the first high-tech enterprise in China dedicated to RNA molecular diagnostics, the company has secured nearly RMB 300 million in financing from investment institutions such as Qiming Venture Partners, Huagai Capital, and Yida Capital. According to Dr. Ju, Rendu Biotechnology achieved profitability in 2017 and plans to initiate its IPO process in 2019.

Rendu Biotechnology has developed multiple series of in vitro diagnostic (IVD) test kits for applications in reproductive health, respiratory diseases, enterovirus infections, and food microbiology. Among these, its flagship product, the “Mycoplasma genitalium Nucleic Acid Detection Kit,” is the first Mycoplasma genitalium detection product in China to receive certification from the China Food and Drug Administration (CFDA). The combination of advanced specific magnetic bead extraction technology with SAT technology has made “non-invasive urine testing” possible, and the product has been promoted in more than 300 hospitals across China. Dr. Ju Jinliang told VCBeat (WeChat ID: vcbeat) that the AutoSAT fully automated analyzer, jointly developed by Rendu Biotechnology and a Swiss team, will be launched in January 2019. “With the launch of AutoSAT, Rendu Biotechnology will achieve dual-driven growth through both kits and instruments, accelerating product coverage.”

According to Dr. Ju Jinliang, SAT is a second-generation nucleic acid detection technology that surpasses PCR. The SAT technique reverse transcribes extracted template RNA into cDNA, which is then transcribed into abundant RNA products. Molecular beacons bind to the amplified RNA, emitting fluorescence, thereby enabling real-time fluorescent isothermal amplification detection of RNA. Compared with PCR, SAT features four major characteristics:

First, the test targets RNA, offering high sensitivity. It can distinguish between latent and active infections, as well as between dead and live bacteria, thereby assisting in the assessment of cure. Dr. Ju Jinliang told VCBeat that while DNA can persist for more than three months after cell death, RNA typically disappears within two weeks. Therefore, RNA testing can be used to aid in evaluating treatment efficacy. “This feature is highly significant in the field of reproductive health.” In terms of sensitivity, PCR achieves a 95% detection rate for Chlamydia, whereas SAT can increase this rate to 98%.

Second, RNA is captured and purified using magnetic beads to remove various impurities (including diverse inhibitors) from the sample, thereby preventing inhibition of the amplification reaction and enabling urine-based detection.

Third, the amplification product is RNA, which is prone to degradation and susceptible to hydrolysis by airborne RNases, thereby reducing the risk of contamination from amplification products.

Fourth, isothermal amplification at a constant temperature of 42°C enables rapid detection, with the entire amplification and detection process taking only 40 minutes. The total turnaround time from sample extraction to result acquisition is 80 minutes, whereas conventional PCR-based molecular diagnostics require more than 2 hours.

Although, in theory, SAT technology can cover all diseases detectable by PCR, and molecular diagnostic techniques can identify conditions that are undetectable or have extremely high false-negative rates with immunodiagnostic and biochemical diagnostic methods, molecular diagnostics is still in its early stages of development. While traditional diagnostic methods can detect hundreds of diseases, and PCR technology can detect up to more than one hundred, SAT technology has currently achieved clinical detection for only a dozen or so diseases.

Dr. Ju Jinliang believes that the clinical value of molecular diagnostics has seen a substantial improvement compared to immunodiagnostics and biochemical diagnostics, and with time, it will achieve broader application.

In terms of the market, RNA detection technology has a high barrier to entry, with few competitors in the domestic market. Rendu Biotechnology’s IVD products demonstrate significant competitive advantages in specific niche segments. Dr. Ju Jinliang pointed out that companies currently focusing on RNA detection are primarily overseas enterprises. Among them, only one U.S. company specializing in human papillomavirus (HPV) testing has entered the Chinese market; however, due to differences in targeted disease types, it engages in differentiated competition with Rendu Biotechnology.

RNA testing products must currently enter the market through molecular diagnostic laboratories that meet specific criteria, with qualified hospitals serving as the primary application scenarios. At present, immunoassay and clinical chemistry diagnostics remain the mainstream disease detection methods in hospitals. Rendu Biotechnology has adopted a market strategy of penetrating from large tertiary Grade A hospitals to primary care institutions.

After discussing the technical advantages of SAT, Dr. Ju Jinliang shared his understanding of innovation in diagnostic methods with the reporter, stating, “All diagnostic innovations should be innovations in diagnostic value.”

He explained that innovation in diagnostic value should encompass three key factors: first, enhancing sensitivity and reducing the rate of missed detections to identify more difficult-to-diagnose diseases; second, optimizing the quality and improving the stability of diagnostic reagents; and third, lowering the stringent requirements for application scenarios, thereby enabling in vitro diagnostics—previously confined to large tertiary hospitals—to be implemented at the primary care level and expanding the patient population served. The outcome of diagnostic innovation should have a substantial impact on patients. “For diseases that were previously undetectable or required multiple repeated tests for confirmation, innovative diagnostics should enable convenient, affordable, and single-test detection.”

Subsequently, Dr. Ju Jinliang introduced the upcoming AutoSAT to VCBeat. AutoSAT is an automated instrument platform jointly developed by Rendu Biotechnology and a Swiss team, which has finally reached the market after eight years of iterative trial and error and three technical version updates. Rendu Biotechnology invested over RMB 100 million in the research and development of AutoSAT. Dr. Ju Jinliang candidly acknowledged that capital support and the patience of its personnel played crucial roles in the development process of AutoSAT.

AutoSAT achieves full-process automation while ensuring testing quality, simplifying operational procedures and significantly lowering the requirements for application scenarios. Dr. Ju Jinliang regards the market launch and promotion of AutoSAT as a turning point for molecular diagnostics to truly enter large-scale clinical application.

Previously, due to the high initial sample volume requirements of conventional molecular diagnostic instruments, samples collected on the same day often yielded results only by the next day, thereby limiting the application of molecular diagnostics to inpatient wards. AutoSAT initiates testing with a single sample and delivers results within 100 minutes, with a maximum daily throughput of over 200 RNA tests. This capability expands the application scenarios of molecular diagnostics to hospital emergency departments and outpatient clinics.

Furthermore, AutoSAT is easy to operate and does not need to be performed in a molecular diagnostics laboratory, thereby expanding the potential medical market from over 3,000 hospitals to more than 30,000 hospitals. “After the launch of AutoSAT, the number of hospitals covered by Rendu Biotechnology will exceed 600 within two years.”

Finally, Dr. Ju Jinliang analyzed that molecular diagnostics will gradually transition toward semi-automated and fully automated systems, shift from specialized molecular laboratories to general laboratories, and decentralize from inpatient wards to outpatient clinics. Rendu Biotechnology is committed to promoting this trend. “Our team consists of more than 150 members, with one-third engaged in market education,” said Dr. Ju Jinliang. “However, the efforts of a single enterprise are inevitably insufficient.”

Rendu Biotechnology will persist in expanding its portfolio by 1–2 diseases annually where SAT technology can enhance detection sensitivity, and Dr. Ju Jinliang hopes to collaborate with more technical experts to advance this initiative.