OPTOLANE Exploits the ‘Semiconductor-based PCR’ for POC·Liquid Biopsy
입력 2018-09-11 09:41 수정 2018-09-11 09:41
by Euna Lee
OPTOLANE, the in vitro diagnostics company, is now developing the ‘Semiconductor-based in vitro Diagnostic Platform’ by using the fluorescence image sensor integrated with thermal control system.
OPTOLANE is heading for exploitation of the platform in the field of the early diagnostics of diseases, and the studies on cancers through ‘point-of-care (POC)’ and ‘liquid biopsy’. OPTOLANE is developing portable real-time polymerase chain reaction (PCR) and digital PCR products through an implementation of the CMOS bio-sensor technology born in SiliconFile Technologies, Inc. back in 2007.
OPTOLANE is also developing the ‘All-In-One PCR system’ as well, where extracts the DNA/RNA from a tiny amount of specimen, runs Real-Time PCR, and analyzes PCR results in the series of automatic process.
Do Young Lee, the CEO and President of OPTOLANE, founded SiliconFile Technologies, Inc., a fabless IC design company that specialized in first-generation CMOS image sensors, in 2002, and his career since then has been as a CTO, and a CEO later. When he sold SiliconFile Technologies, Inc. to SK Hynix Inc. in 2014, he also bought the equipment for the Bio R&D business and corresponding intellectual properties to OPTOLANE.
1. Semiconductor-based Real-time PCR… “Developing POC Molecular Diagnostics for Mosquito-borne Viruses etc.”
The core technology of OPTOLANE is the integration with CMOS fluorescence sensor and the thermal control device into a single chip. OPTOLANE developed the cartridge that is enabled to process real-time PCR on the chip.
Lee said, “you may consider this small cartridge including the semiconductor chip to be a disposable PCR device. The weight of the PCR analyzer is even less than 1 kg, which is good to be portable. We use two step PCR, which takes less than 20 minutes.” The technology of OPTOLANE also has the advantage of multiplexed test available.
The MEMS well array, like the PCR tubes on the qPCR instrument, enables analyses of multi-targeted genes. OPTOLANE plans to employ the semiconductor-based real-time PCR technology for the development of diagnostics for infectious diseases.
The multiplex PCR reagent products capable of diagnosing five kinds of mosquito-borne viral diseases, such as Zika, Dengue, and Yellow fever, etc., have already been developed. Currently, clinical trials are in progress in three hospitals in Mexico and Brazil to go to overseas’ markets of Southeast Asia and of Central and South America.
The company also announced that development is in progress of other products detecting 16 species of respiratory viruses, and 12 species of bacteria causing sexually transmitted infections (syphilis, gonorrhea, and chlamydia, etc.).
2. Digital Real-Time PCR, "Applicability to Liquid Biopsy for Early Diagnostics”
OPTOLANE mounted ‘Digital PCR (dPCR)’, the third-generation PCR technology, on the CMOS-embedded cartridge. Different from the ‘Real-time PCR’ that can give relative quantification through the laborious comparison work with standard samples, ‘Digital PCR (dPCR)’ enables users to get absolute quantification right after PCR without standard sample. Not only the absolute quantification, but it also gives much higher detection sensitivity than real-time PCR does.
‘Digital PCR (dPCR)’ is expected to be applicable to the field of early diagnostics through liquid biopsy, because it can quite effectively detect cancer genes (the circulating tumor DNA (ctDNA)), which are originated from cancer cells and remaining in blood in very tiny amount.
Lee explained, “we have identified precise copy number of gene from the digital PCR results with the low concentration sample. In particular, OPTOLANE’s digital PCR is ‘Digital Real-Time PCR’ which can detect gene in real-time. The real-time curves, as well as final copy number, will be available together; thereby, users would not be worrying about false-positives, or false-negatives either, when it comes to clinical diagnostics.”That is, it can provide users precise, accurate, and reliable quantification results.
The hardware has also been made into compact format. The instrument set of the Droplet Digital PCR (ddPCR) of Bio-Rad, which occupies 40 % of current market share, consists of three units of sample loading, PCR process, and analytic reading.
OPTOLANE is implementing their Digital PCR system to do digital PCR process and analysis in the single system unit with the cartridge where 20,000 well chips are mounted. This can makes OPTOLANE to maximize user convenience and also reduce the price of digital PCR instrument compared to existing instruments. It takes less than an hour for the digital PCR preparation, operation, and result-out.
The feasibility to liquid biopsy and single cell analysis was also identified. The company thus expects their PCR system would be applicable to studies exploring the mutation of cancer cells through tissue biopsy and liquid biopsy.
3 All-in-One Real-time PCR for POC, “An Integration of DNA Extraction, PCR, and Analysis”
OPTOLANE now steps further ahead. The ‘All-in-One Real-time PCR’, where the preparation of DNA/RNA specimens and real-time PCR process are integrated, is currently being developed. The design concept aims for simpler, smarter, and smaller analysis system, leading to POC molecular diagnostics. The all-in-one cartridge configures a single entity with semiconductor-based PCR chip and sample preparation device. It is a ‘Sample-to-Answer’ concept, consisting of the preparation of specimens, PCR, and analyses.
Lee stated, “… we are dreaming of becoming a global player in the fields of, point-of-care molecular diagnostics, liquid biopsy, and research on diverse diseases through the semiconductor-based PCR platform…”.
Based on the differentiated platform technology for diagnostics, OPTOLANE succeeded in funding for investment of 6.5 billion KRW (for Series A) in 2015, 10 billion KRW (for Series B) in 2017, and 12 billion KRW recently in August this year. The secured investment will be exploited for the expansion of production facilities and reinforcement of human resources for product development, commercialization, and making steps into overseas markets.