Ricoh’s Bioprinting Technology Could Help Improve PCR Testing

Seeking ways to uncover new customer applications in the biomedical field led Japanese multinational imaging and electronics company, Ricoh, to develop a proprietary bioprinting technology that is now being used to control DNA molecule-by-molecule to accurately detect trace amounts of virus in genetic testing. More particularly, this is being done in polymerase chain reaction (PCR) testing, a tool used for medical testing which has become a familiar household name around the world ever since the COVID-19 pandemic began.

Ricoh will now be marketing their newly developed Ricoh Standard DNA Series as reference material for genetic testing applications where PCR is used, to overcome challenges in PCR testing. The Standard DNA Series enables a specific number of DNA molecules, in units of one, to be injected into containers used for genetic testing applications, which according to the company, means that the accuracy of detection in PCR tests can be assured even in low concentrations of under 100 molecules.

The PCR high-performance genetic testing method invented in 1985 by Kary B. Mullis can detect all types of bacteria, parasites, viruses, and fungi, starting with DNA or RNA by selectively amplifying trace amounts of genetic material, identifying specific parts of the DNA. It can potentially detect DNA even at the level of a single molecule by amplifying it. However, Ricoh indicated that, in reality, extremely small amounts of DNA cannot be detected in some tests because of inadequate precision control in the apparatus or imperfect performance and quality of reagents, leading to false negatives, where viruses cannot be detected even though the person is infected, and this makes accurate diagnosis of viral diseases challenging.

In fact, scientists in the US have warned that there is a growing concern from the over-reliance of COVID-19 testing since the majority of the tests around the world use PCR technology to detect traces of the coronavirus in mucus samples, and these are not 100 percent reliable.

Evaluation of reference DNA plate for the novel coronavirus SARS-CoV-2 by real-time PCR*3 (Credit: Ricoh)

By leveraging its bioprinting technology, Ricoh has created new value through innovation. In fact, the company has now expanded the use of this product by developing reference DNA plates for specific types of viruses, including the novel coronavirus SARS-CoV-2, instead of just supplying reference DNA plates for noroviruses – one of most common viral causes of gastroenteritis. For now, these plates are only available in Japan.

Ricoh suggested that the accuracy of PCR tests is determined by their sensitivity and specificity. Sensitivity refers to the proportion of cases in which people infected with the virus (true positives) are correctly identified as positive. Specificity refers to the proportion of cases in which people who are not infected with the virus (true negatives) are correctly identified as negative. They claim that one of the reasons for inaccurate detection may be insufficient verification of the sensitivity and specificity of the PCR test. In addition, there are detection limits with PCR testing when trace amounts of a virus below a certain limit cannot be detected. In the event a sample has a viral level below the detection limit at the time of the test, the result of the PCR test will be negative, even if the virus is present in the sample, and consequently, the result will be a false negative and can lead to new infections because patients carry out daily activities without realizing they are infected. Reducing false negatives can contribute to reducing the risk of infection spreading.

To verify the detection limit and the sensitivity of PCR testing, and to accurately measure and control the performance and quality of test instruments and reagents, it is necessary to use reference material where the number of DNA molecules is specified accurately as a standard in the test. Reference materials for genetic tests have already been supplied by several companies and research institutes, but they are highly concentrated materials and even though high-concentrations are ok, it has been difficult with low-concentrations of less than 100 molecules to judge whether or not the measurement is accurate.

Solving this problem in PCR testing has been achieved by Ricoh. They claim that their product uses bioprinting technology with a unique inkjet method to dispense DNA molecules into the wells of plates or tubes for genetic testing in units. This means that there is no variation in the number of DNA molecules, even at low concentrations, and it makes it possible to exercise strict precision control and quality control over genetic testing methods, testing devices, and reagents. The number of DNA molecules injected per well can also be increased incrementally as required.

According to Ricoh, in order to precisely verify genetic tests, devices, and reagents, researchers need a scale or benchmark in which the number of DNA molecules is determined. Through joint research, Ricoh has developed a technology to manufacture a container of a prescribed number of DNA molecules, called a reference DNA plate. And because the number of DNA molecules is accurately controlled molecule-by-molecule, the technology will enable stricter quality control of genetic testers, reagents, and genetic testing methods as well as increase the reliability of genetic tests.

Headquartered in Tokyo, where the company operates its proprietary 3D bioprinter technology, Ricoh will begin marketing its newly developed Ricoh Standard DNA Series as reference material for genetic testing applications where PCR is used.

In the future, Ricoh hopes to expand the applications of the Ricoh Standard DNA Series to precision control of genetic testing methods and reagents, to handle unknown infectious diseases and contribute to virus-free tests (tests that certify the absence of viruses) used in the manufacture of regenerative medicines and biopharmaceuticals.

As more companies begin to flood the biomedical field, aiding with research, leveraging bioprinting technology, and creating new venues for institutes and laboratories to expand their innovation, new and dedicated applications and discoveries help the industry advance quicker than ever before. Hopefully, widely recognized changes, like Ricoh’s new development and move into the bioprinting realm, will engage more companies to transform their technology and invest in bioengineering, life sciences, and other industries of the future, which are elemental to our survival.