Maximum signal quality even at low light levels

Progress in life sciences is closely linked to the further development of photonic components. Precision light sources, photodiodes, photon counters and CMOS sensors give medical and scientific researchers in-depth insights into the building blocks of life. Whether it be PCR (Polymerase Chain Reaction) tests for detecting the coronavirus, DNA sequencing, blood analysis using flow cytometry or OCT (Optical Coherence Tomography) tissue examinations, the technological core is photonic. In the interview, Philip Waldner and Tina Urbanek, two experts in the area of medical technology/biophotonics from HAMAMATSU PHOTONICS Deutschland GmbH, discuss the role of optoelectronics and photonics in medical innovations, the impact of Covid-19 on their area of business and current technological trends in medical imaging.

Mr. Waldner, can you give readers who are not familiar with HAMAMATSU PHOTONICS a brief insight into your company and its activities in Germany?

Philip Waldner: We are a global company with headquarters in Hamamatsu, Japan and sites in the U.S., Asia, and various locations in Europe. We employ just under 5,300 people, 120 of them in Germany. HAMAMATSU PHOTONICS develops and produces photodiodes, light sources, and other photonic and optoelectronic components which we supply to customers in a range of sectors. Our most important markets include chemical analytics and medical technology as well as car manufacturing and safety technology. The majority of our research, development and production is carried out in Japan. In Europe, we have established sales and service departments as well as software teams. We not only provide standard products for our customers – we also help them to integrate our components and modules and adapt them to their specific requirements.

HAMAMATSU offers a range of sensors, light sources, cameras, and optical components as well as analytical devices. Are you a system integrator or supplier of components?

Waldner: We see ourselves primarily as a component supplier. We generate 40 percent of our global turnover with medical technology; components for X-ray systems account for 27 percent and solutions for laboratory devices for 13 percent. In both markets, our customers come to us with specific requirements and our engineering department then adapts our products accordingly. Incidentally, our solutions in the area of X-ray technology too are primarily of a photonic nature. For example, our scintillators convert X-rays into light which can be detected by sensors. This conversion takes place in a crystalline scintillator layer which we integrate into semiconductor sensors. These sensors are used in X-ray machines around the world.

Since the pandemic started, everyone has been talking about PCR tests. What role does photonics play in detecting a coronavirus infection?

Tina Urbanek: At the heart of qPCR devices is an optical unit which detects fluorescent or colorimetric signals given off by specific molecules in the virus. Because the signal from isolated viruses in the samples is too weak, they are amplified via Polymerase Chain Reaction under optimum temperature conditions over a number of measurement cycles. Because this amplification takes place exponentially, the fluorescence signal in the case of positive samples becomes stronger with each cycle. Silicon photodiodes, cameras and spectrometers are used for detection purposes. We contribute modular multi-pixel photon counters (MPPC), photosensor modules and CMOS camera modules which record the fluorescence signals. We provide the necessary photonic know-how, while our customers have the medical analysis skills.

How has growing global demand for PCR devices affected your business?

Waldner: The growing demand for reliable systems for detecting Covid-19 is without doubt one of the reasons why we now generate 13 percent of our global turnover with components for laboratory devices. Research and development activities in this market segment have grown significantly. The focus is also on antigen tests, other liquid analysis procedures and non-invasive measurement methods—we provide high-tech photonic and optoelectronic components for this. Even if it is already used in a wide range of areas, photonics remains a future technology which is driving progress in the field of medicine. From X-ray machines and other imaging procedures to blood analysis using flow cytometry, in-vivo tissue examinations via OCT (Optical Coherence Tomography) or DNA sequencing which is now indispensable…

You provide multi-pixel photon counters for this. What is important when it comes to this technology?

Urbanek: The signal to noise ratio is crucial here. Our MPPCs are essentially silicon photomultipliers, i.e. semiconductor technology. We have years of experience in this area. The origins of our company lie in vacuum tube technology for televisions—decades ago, we enabled this technology to be used in photomultipliers. Because they can be used to detect even the tiniest quantities of light, our tube-based approach is still in demand. We have also applied this know-how to the semiconductor technology used in laboratory devices where space is limited. Our MPPCs have a high internal amplification factor, minimal noise, and a high temporal resolution. Thanks to the multi-pixel sensor, they offer highly efficient photon detection too. That is the key to precise fluorescence detection.

Thanks to miniaturization, mobile devices for water, gas or soil analysis are becoming increasingly accurate. Is this trend being seen in the field of medical analytics too?

Urbanek: We are seeing increased demand for solutions which allow mobile diagnostics and analytics at the point of care. The focus of our R&D activities is therefore on miniaturized modules and components. Semiconductor MPPCs as an alternative to tube photomultipliers are a good example. The same applies to our mini-spectrometers and many other optical sensors.

Waldner: The development of mobile X-ray machines for X-raying patients during operations or in their hospital beds is another interesting area. We offer a wide range of detectors with optical filters for mobile gas analytics. The smallest wavelength-filtered quantum cascade laser available on the market which was unveiled by our R&D colleagues in Japan last summer is probably worthy of mention here. With exterior dimensions of 13x30x13 mm, it is 150 times smaller than its predecessor and is ideal for mobile analysis devices. It is currently being tested as a way of detecting sulfur dioxide and hydrogen sulfide in the gas released from volcanoes. Regular gas monitoring could be the key to predicting eruptions early on.

Where do you see important photonics-driven technological trends in medicine and life sciences—and how is HAMAMATSU contributing to this?

Waldner: In human medicine and other in-vivo imaging procedures, the trend is moving towards achieving increasingly better signals and higher image quality with lower and lower radiation and light intensities. Non-invasive methods are also in demand for the gentlest diagnostic procedures possible. Both trends involve detecting very weak light signals. That is exactly what we are working on. The aim is to optimize the signal to noise ratio so that clear evaluations are possible even with very low light intensity. Low-noise hardware solutions which are able not only to recognize incoming signals but also to amplify them within the sensor are needed here. This requires a great deal of photonic, optoelectronic, and material science know-how—know-how which HAMAMATSU has been building up since 1953.