Biosensors enablenew approach to viral tests

More than three years have passed since the official declaration of the Covid-19 pandemic, and the viral spread looks set to continue. People everywhere are looking for ways to prevent new infections while also returning to normal daily life. But no matter how careful we are, there is no way to completely stop the spread of Covid-19.

One of useful tools used to slow the spread of infections is virus detection technology.

But we realized that it is difficult to flexibly deploy rapid and sensitive detection equipment suited to current pandemic conditions, and that it is also difficult to share and utilize the results for the medical-treatment and infection-prevention countermeasures.

Medical institutions aren’t the only places who face such challenges: industrial production lines, for example, have to suspend operations to carry out disinfection; schools are forced to close; events and lectures are canceled; restaurants face restrictions on opening hours and activities. All of situations have major impacts on economic activity throughout society.

If there were some easy-to-use and accurate devices that also provided quick results, it would greatly help prevent infections and ease the strain on medical institutions and the economy.

In order to address these issues, DENSO is developing biosensors that offer highly sensitive and rapid detection.

These biosensors offer four main advantages: they are small and easy to use anywhere, they are simple for anyone to use, they provide immediate results, and they quickly respond to new virus types. Thanks to these advantages, biosensors have the potential to change how society handles and lives with infectious diseases.

The detection devices offer high sensitivity and, unlike PCR tests, do not require specialized skills to use. Moreover, it takes only 15 minutes to get a result, and the result is further converted into a digital format to facilitate data management. Kazuhisa Nakagawa of DENSO’s R&I department of Material R&I Div. explained how he thinks society will be changed by the biosensors as follows.

“I believe we can create an extremely compact product comprising a sensor within a cartridge unit. By making the [detection] device very small, it can be used even in medical clinics. The first product will be about the size of a laptop computer, and eventually we hope to reduce the size of the next one to that of a smartphone. In the future, it will be possible to test viruses freely.”

By popularizing this type of biosensor device, it may be possible in the future that cloud storage of geotagged test result data enables you to take the trouble out of collecting and organizing them. It would also help to predict the numbers of hospital beds, medicines and vaccines to be required.

Nakagawa added: “By providing immediate test results, it will be possible to speed up medical treatments and measures, and thus prevent infections from spreading further. My vision for the future is that anyone can obtain test results immediately anywhere, and then share them in real time.”

Spreading such highly sensitive and compact detection devices can greatly reduce the burden on medical institutions and workers. Furthermore, automatic digitalization of test results will make it possible to understand infection situations in more detail to facilitate more effective countermeasures.

DENSO’s biosensors utilize aptamers and semiconductors. Aptamers are artificial nucleic acid fragments designed to bind to particular molecules.

For Covid-19 tests, aptamers that selectively bind to the virus are used. The aptamers are specially designed to amplify the electrical signals, and a specific type of semiconductor-based sensor known as an ion-sensitive field-effect transistor (ISFET) detects the signals from the aptamers. This enables high-sensitivity detection at nearly the same level as PCR tests.

Standard virus tests use light and color for visual or camera-based determinations. For the light-based detection, an external photodetector is required, which limits how small the detection device can be made.

With biosensors, in contract, changes of ion concentration within a liquid solution can be measured, and thus no external optic apparatus is required. This offers the advantage of high detection sensitivity coupled with the extremely small device size.

R&D on DENSO’s biosensor started as part of a project to create a device that could reduce traffic accidents, dating back to before the Covid-19 pandemic. Akira Nukazuka from the Material R&I Div. described it as follows:

“We started this [biosensor] research with the goal of preventing traffic accidents caused by myocardial infarctions, cerebral infarctions and other such conditions. These conditions are caused by the common malfunction: blood vessel clotting. Therefore, by indicating the severity or presence of the vessel clots through the analysis of specific biomarkers using this biosensor, we hoped that it would serve to prevent traffic accidents caused by such diseases. We started the research around 2013.”

Afterwards, the project extended the application of the technology around 2019 in the context of the sharing-economy. With the car sharing system, it is important to keep the environments of cabins clean, because they are used by multiple users. This is why there came huge demand for sensing technologies that could detect infectious viruses and pathogenic bacteria.

In addition, when the Covid-19 viruses began to spread, development of the current biosensing technology has been accelerated, thanks to the funding from the Japan Agency for Medical Research and Development (AMED). Through these processes, this technology has been established.

According to Nakagawa, DENSO has the strength that multiple specialists majoring in a broad range of technologies including semiconductor, biotech, and chemistry gather in a single R&I division. This is how DENSO has succeeded in breaking into this unexplored biosensing field.

“We utilize frameworks that are only possible with abundant experience and know-how in all of these technologies—not just one alone. The reagent we use for our approach includes materials that are suitable for semiconductor-based sensors. The sensors, on the other hand, have circuitry and signal-processing capabilities that are designed to respond to those materials in the optimal fashion.”

Most companies focus on antibodies, whereas DENSO is focusing on aptamers, and this gives DENSO certain technological advantages. The production of antibodies requires living organisms or cells, whereas aptamers can be synthesized via chemical reaction.

Even if viruses mutate later, it’s possible to quickly prepare new aptamers, as they can be artificially and quickly synthesized.

In collaboration with medical institutions, DENSO is leveraging its wealth of experience and knowledge in industrial robots and other technologies to accelerate verification testing. Development has been supported by DENSO WAVE Incorporated.

These biosensors are expected to be used not only for Covid-19 detection, but also for other applications such as allergen and cancer detection.

According to Nukazuka, “For example, specific molecules known as tumor biomarkers are indicators of specific types of cancer. These biomarkers increase in quantity the more serious the cancer becomes, meaning the amount of biomarkers indicates the severity and progression of the disease.”

In the past several decades, our society has experienced outbreaks of infectious diseases including influenza, SARS, MERS, and now Covid-19. Nobody knows when the current pandemic will end, or when the next one will strike. By finding ways to avoid panicking again when the next pandemic does hit and enabling more flexible responses, it will be possible to reduce stress for everyone involved. That’s why DENSO seeks to cultivate a society where everyone feels safer in their daily lives.

In order to achieve a framework for this type of society, collaboration with other companies and organizations that share the common goals and values is key. Moving forward, DENSO will work closely with partners from the prototype development phase to facilitate rapid deployment of practical detection devices throughout society. According to Nakagawa and Nukazuka, DENSO aims to develop an appealing business plan, promote interest in these efforts while seeking like-minded partners, and focus on technological development.

In these ways, DENSO hopes to achieve its vision of deploying biosensors that make life safer and improve well-being for people everywhere. To ensure that this project becomes a reality, DENSO is sharing its vision widely to foster understanding and interest, while also searching for new partners who can help realize the vision at the earliest date.

Project members (from left): Nakagawa (in charge of Development of semiconductor-sensors and systems), Nukazuka (Project leader), Mana Kanazashi (in charge of R&D of aptamers), Kei Hayakawa (in charge of R&D of biosensing reagents and detection-processes)