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medical diagnostics

SEMI spoke with Dr. Franz Laermer, Research Fellow (Senior Chief Expert) at Robert Bosch GmbH Stuttgart, Corporate Sector Research and Advance Engineering, about the latest trends in medical diagnostics and personalized treatments. An open platform for the automation of complex molecular diagnostics workflows recently developed by Robert Bosch has proven its ability to take molecular diagnostics to the point of need.To make this happen, miniaturization, microsystems and microfluidics technologies, as well as microelectronics, are crucial. This is critical for the detection of SARS-CoV-2 infections within a rather short development time.Laermer shared his views ahead of his presentation at the SEMI MedTech Forum, 19 February, as part of the SEMI Technology Unites Global Summit, 15-19 February 2021, online event. Join us to meet experts from Robert Bosch and other key industry influencers. Registration is open. SEMI: What is driving innovation in diagnostics and what role does the semiconductor industry play?Laermer: One of the major drivers in diagnostics is the molecular breakdown and detailed analysis of nucleic acids on the level of the individual nucleotide. This reveals the root causes of diseases like cancer, genetic aberrations, infections and therapy resistances. Today’s solutions are mostly PCR-based (that rely on the polymerase chain reaction) or depend on sequencing. The keys to bring these technologies closer to the point of need are automation, miniaturization, low-cost, ease of use, flexibility, reliability, and fast time from sample-to-result. Semiconductor and microsystems technologies are enablers to meet these requirements, thanks to their ever-increasing performance, with Moore’s law pushing the semiconductor side of the story.SEMI: Can you tell us more about the the Bosch VIVALYTIC system? Laermer: VIVALYTIC is a universal and highly flexible diagnostic platform for the integration and automation of a wide variety of molecular diagnostics assays. It consists of the universal laboratory analyzer tool, which operates the application-specific cartridges. All reagents and specific bio contents are contained in the application-specific cartridges in a long-term stable manner at room temperature. The user only has to introduce the patient sample into the cartridge, push the cartridge into the analyzer and start the automatic workflow, which yields a diagnostic result within typically less than one hour. The VIVALYTIC products are manufactured by Bosch Healthcare Solutions GmbH (BHCS) in cooperation with strategic diagnostic partners and bio content owners.SEMI: How is the pandemic impacting automated diagnostics in the medical industry? What is new now?Laermer: The pandemic has clearly shown the importance of fast automated diagnostics at the point of need. Breaking infection chains as early as possible requires fast reliable PCR testing anywhere and anytime. We managed to reduce the time needed for SARS-CoV-2 rapid testing to less than 30 minutes for positive probes, an achievement that is embraced by our customers. Until a sufficiently high level of immunization is reached by vaccination, rapid testing is the only way to limit the number of infections, hospitalizations, and lethal outcomes of the COVID-19 pandemic.SEMI: Besides infectious disease diagnostics, what solutions will enable a paradigm shift in medical treatments?Laermer: Today more and more targeted drugs and therapies are developed in oncology to address certain mutations that are considered drivers of the cancer. This moves away from the one drug fits all approach to precision oncology. As a prerequisite of this personalized therapy, the mutation status of a tumor must be clarified – and monitored precisely and repetitively during therapy. The latter requires molecular diagnostics at the point of need, i.e. at the onco-ambulance. One keyword in this context is liquid biopsy. Another example of personalized therapy is the detection of bacteria type and antibiotics resistances in bacterial infections, and the selection of optimized antibiotics therapy.SEMI: What solutions can Robert Bosch bring to address the needs just mentioned? Laermer: Robert Bosch GmbH is a leader in microsystems, microsensors and semiconductor technologies. Our new 12-inch semiconductor plant in Dresden will strengthen our position in these fields. This encompasses artificial intelligence and the Internet of Things as well. As a technology provider, we generate superior solutions for automation and management of complex workflows, and thus deliver win-win-solutions together with our diagnostic partners.SEMI: How can technology unite us? Laermer: Technology, especially semiconductor and microsystems technology, is a game changer in the medical area. Whenever different disciplines meet each other and cooperate, as are the medical, diagnostics and semiconductor areas, innovation is accelerated strongly. New things happen at the interfaces between different areas of competencies.Franz Laermer, Research Fellow (Senior Chief Expert), Robert Bosch GmbH Stuttgart, Corporate Sector Research Advance Engineering. Dr. Franz Laermer joined the Corporate Research and Technology Center of Robert Bosch GmbH, Stuttgart, Germany, in 1990, where he started the development of new key technologies and sensor functions for the upcoming field of MEMS at Bosch. Today he is a Bosch Research Fellow/Senior Chief Expert for Microsystems, Microfluidics and Molecular Diagnostics. Laermer's work laid the foundation for the VIVALYTIC Diagnostics Platform of the newly founded Bosch Healthcare Solutions (BHCS) Business Division and the SARS-CoV-2 rapid tests from Bosch. Dr. Franz Laermer is the co-inventor of the Bosch Deep Reactive Ion Etching Process (BOSCH-DRIE) for microstructuring silicon. He holds more than 200 patents and was awarded with European Inventor of the Year 2007 – Category Industry prize by the European Commission and the European Patent Office (together with co-inventor Andrea Urban) for the invention, development and sustainable success of the BOSCH-DRIE process. He received the 2014 IEEE Jun-ichi Nishizawa Medal Award from the Institute of Electrical and Electronics Engineers (IEEE), USA. In 2019 he was awarded with the 2019 Technology Prize from the Eduard-Rhein-Foundation in Germany.Serena Brischetto is senior manager of Marketing and Communications at SEMI Europe.
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VTT Technical Research Centre of Finland Ltd (VTT) has its sights set high. As a leading global research and development firm , VTT is out to produce bio-interfacing and biodegradable flexible hybrid electronics (FHE) devices that help tackle some of the world’s greatest challenges including environmental degradation and food scarcity.SEMI’s Maria Vetrano interviewed Antti Vasara, president and CEO of VTT Technical Research Centre of Finland, to preview his February 25 keynote, Beyond Flexible Hybrid Electronics: Biodegradable Electronics and Interfacing Bio+Electronics, at FLEX|MEMS Sensors Technical Congress (MSTC) 2020, February 24-27 at the DoubleTree by Hilton in San Jose, California. Join us at FLEX|MSTC to meet Antti and other industry influencers driving innovation in flexible hybrid electronics (FHE) and MEMS sensors. Register now to connect with him at FLEX|MSTC or visit him on LinkedIn.SEMI: What is body-interfacing electronics and what is your vision for bio-interfacing and biodegradable electronics?Vasara: Body-interfacing electronics have existed for decades. Developed in the 1970s, the wireless heart rate monitor is a good example. While continuous heart monitoring with a compact, inexpensive wearable device is widely accessible technology, other bodily parameters, such as cholesterol levels or biomarkers, are diagnosed every time we see a doctor. Establishing a baseline using multiple measurements — before symptoms develop is actually much more effective.That’s where bio-interfacing comes in. Bio-interfacing devices will continuously measure and analyze complex biogenic substances such as sweat, breath, blood and urine. A smart patch for continuous sweat monitoring, for example, would overcome several challenges: supporting electronics functionality in liquid environments, managing the transport of harvested samples to and from the sensor, managing potential contamination, and disposing of samples after measurement.While FHE in principle delivers the right building blocks and is an ideal form factor for a wearable sweat analytics patch, flexible circuits are not ready for out-of-the box interaction with biological matrices. Hence, our mission at VTT is to anticipate and develop the upscaling process know-how required for FHE devices that either interface with biological systems — or that must themselves biodegrade.We’re also focusing on biodegradable electronics because environmentally conscious end-users and manufacturing companies want biodegradable versions of energy-autonomous, label- or sticker-like Internet of Things (IoT) sensors. Typically used for packaging, logistics, environmental monitoring and medical diagnostics applications, these sensors — which have a lifetime of a few days, weeks or months — have become very popular. Unless they are biodegradable, however, they just add to landfill.SEMI: What approaches is VTT using to develop bio-interfacing and biodegradable electronics?Vasara: In our Business Finland-funded ECOtronics project, we are working with our partners to create recyclable and compostable electronics and optics that use renewable resources. For example, devices developed using substrate materials like paper, cardboard or VTT’s in-house-developed nanocellulose films and biopolymer films for environmental monitoring or skin patches can be easily recycled or even biodegrade naturally. Where possible, we use roll-to-roll printing to generate the device circuitry, and on a component level, we have optimized our assembly process towards bare-die component bonding to reduce the overall footprint of non-biodegradable waste per device.SEMI: What use cases do you find most promising and why?Vasara: A prominent example of a single-use test that generates a large amount of waste is the digital pregnancy test. When breaking it down into components, you will find a rigid circuit board with microprocessor, a couple of coin cell batteries, a liquid crystal display, a LED light source and photodiode, and a large chunk of plastic packaging around it. The materials and battery capacity of such a device would be sufficient to run hundreds of pregnancy tests – actually technical overkill.By using printed circuits on biodegradable substrates, bare-die assembled components (ASIC, LED light sources, photo diodes, thin film batteries as power sources) and device packaging composed of biodegradable plastics, we can completely redefine the environmental footprint of single-use tests. We are currently developing a toolbox for our customers to turn their existing conventional test into an ecotronic form factor.Another exciting use case is a sweat sensor that we developed collaboratively with Ali Javey, Ph.D., professor of Electrical Engineering and Computer Sciences, UC Berkeley, and the co-director of Berkeley Sensor and Actuator Center (BSAC). Together with his team, we created a wearable electrochemical sensor for continuous sweat analysis during exercise. With the UC Berkeley group providing the chemistry to monitor N+, K+ ion and hydration levels in sweat over the duration of several hours, VTT delivered the underlying sensor platform, featuring the printed sensor electrodes and sweat harvesting microfluidic channels for fluid management and transport. It’s exciting to see what we can achieve by combining techniques from different disciplines, in this case electrochemistry, printing, packaging and microelectronics.SEMI: How can industry enable the development/manufacture of flexible FHE devices? Where does VTT fit into the ecosystem?Vasara: As many FHE devices target large-volume markets, scalability of manufacturing is key: How can I get from one device (= working prototype) to a handful of devices (= feasibility study), to thousands (= pilot manufacturing), to a million (= mass manufacturing) without compromising the quality of the system’s performance and reliability?Access to upscaling infrastructure is essential for the development of novel FHE devices and methods, but infrastructure is expensive. That’s where our establishment of a roll-to-roll pilot printing line to bridge the gap between laboratory R D and mass manufacturing has proved invaluable. We can provide a unique worldwide upscaling infrastructure for advanced FHE devices, with a strong focus on large-area roll-to-roll processes and hybrid assembly. This service removes our customers’ burden of high infrastructure investment in early development stages and it allows us to guide customers along their development path, from prototype to mass production.Watch our video: VTT pilot manufacturing for diagnostics and wearablesSEMI: Is there anything else that device manufacturers need to know in order to succeed?Vasara: In my eyes, the success of FHE devices eventually depends on several factors: It requires a high degree of automation, well-optimized processes, reliable supply chains, and perhaps most importantly, clear standards and rules for designers to guarantee flawless interoperability of all the different elements on a flexible and hybrid circuit. Let us not forget – we are trying to marry electronics with printing, biology, packaging, microfluidics, injection molding and other fields of expertise.We recently finalized the compilation of a set of design rules for publication in our state-of-the-art overview of printed and hybrid electronics manufacturing methods. You can download the overview, PrintoCent Handbook, for free.SEMI: What would you like FLEX|MSTC attendees to take away from your presentation?Vasara: The latest technologies and innovations in microelectronics, MEMS, printing, materials, and biosensors provide us a toolbox for true innovation in the FHE space. Now we need cross-disciplinary thinking and daring steps to combine different manufacturing methods and skill-sets. The ideal cross-disciplinary team might include: The printing engineer who knows how to design contact pads for a bare-die IC assembly The biologist who knows about the thermal and mechanical stress in a printing environment to design processes for bio-functionalization of surfaces The electronics engineer who knows how to optimize a circuit powered with an enzymatic biofuel cell The number of sensors deployed on (or inside) our body, in our drinking water, in our cars, on our fields, in our pets, and everyday products will surely grow. Let us make sure they leave the smallest environmental footprint possible.Antti Vasara, Ph.D. has been the president and CEO of VTT Ltd since 2015. VTT is a visionary research, development and innovation partner with over 2000 people and a turnover exceeding 250M EURO. Vasara is president of EARTO (European Association of Research and Technology Organisations) and is chairman of the board of Palta (Finnish Service Sector Employers). In addition, he is a non-executive director of Elisa Oyj (largest communications operator in Finland) and a board member at EK (Finnish Confederation of Industries).He has served on several high-profile groups on industrial and innovation policy of the European Commission, in addition to several groups in Finland on artificial intelligence and research policy. Previously, Vasara spent close to 25 years in private industry, working at Nokia, Tieto, SmartTrust and McKinsey Company. Earlier in his career, he was a researcher in optical communications with 20+ peer-reviewed articles and one international patent. Vasara holds a Doctor of Science (Technology) degree from Aalto University in Finland.For more information about VTT’s work in bio-interfacing and biodegradable FHE devices, visit VTT Research. FLEX|MSTC is organized MEMS Sensors Industry Group (MSIG) and FlexTech, SEMI technology communities focused on the growth of MEMS sensors and the flexible electronics supply chain, respectively.Maria Vetrano is a public relations consultant at SEMI.
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