microfluidics

Luc Van den hove, president and CEO at imec, spoke on semiconductor sustainability, healthcare trends and deep tech, and their implications for the semiconductor industry, sharing his views ahead of his keynote presentation at SEMI ISS Europe on May 30, 2022, in Brussels, Belgium.

Electronics innovation is inching tantalizingly closer to the day when treating neurological disorders such as epilepsy and migraine could be as easy and convenient as dropping into a medical clinic for a minor medical procedure – brain surgery. What today is highly invasive surgery promises to be reduced to a doctor’s office visit as chip engineers work to tether the delicate, complex neurochemical workings of the human brain to the hard wiring of electronics. The goal is to use electrical stimulation to trigger the release of therapeutic doses of natural brain chemicals using small implantable devices in order to restore normal brain functioning, reduce human suffering and help slash the financial burden to economies around the world. The advances come as neurological disorders remain the leading cause of disability worldwide, afflicting up to 1 billion people, a number projected to rise sharply in the years to come, according to the World Health Organization. In 2015, conditions including dementia, epilepsy, multiple sclerosis, Parkinson’s disease and stroke accounted for more than 94 million disability-adjusted life years (DALYS), the number lost globally to ill-health, disability or early death – a total expected to swell to over 103 million by 2030. In the U.S. alone, brain diseases cost nearly $800 billion each year, according to a paper published in the Annals of Neurology in 2017. Bioelectronics Innovation Outpaces Drug Development The trendlines are heightening the urgency to develop new, effective medical treatments, yet traditional drug development alone may not be able to keep pace: The journey to create drugs ready for pick-up at your local pharmacy takes, on average, 10 years from the time they are hatched in the lab. “Unfortunately, pharma is unlikely to help address this problem because drug discovery is becoming slower and more expensive,” George Malliaras, Prince Philip Professor of Technology at the University of Cambridge, noted in his presentation, Electronics on the Brain, at last month’s virtual FLEX 2021 conference. In marked contrast, microelectronics are “becoming cheaper and faster every year.” Dating back to the 1950s with the development of implantable pacemakers to re-establish normal heart rhythms, bioelectronics medicine could help demystify how the brain processes information and lead to more effective treatments for neurological disorders. The field has come a long way since devising cochlear implants to treat hearing impairments in the 1970s, designing spinal cord stimulators to relieve chronic pain in the 1980s and targeting the brain with electrical impulses to help relieve Parkinson’s disease symptoms and neuropsychiatric disorders in the 2000s. ​Deep Brain Stimulation Implants Help Treat Neurological Disorders Deep brain stimulation involves implanting electrodes in the brain through small holes in the skull to send electrical impulses to specific target areas. Used in the U.S. since 1997 to treat Parkinson’s disease, deep brain stimulation can improve motor skills in patients suffering from other conditions too such as dystonia, tremors and epilepsy, enabling them to “function normally, with the flip of a switch,” Malliaras said. Researchers are even testing the technology to treat autoimmune and other disorders not originating in the brain. But the large, rigid electrodes used in the surgery are hostile to the soft, subtle confines of the brain. What’s more, implanting the devices is invasive, with multiple follow-up surgeries typically needed to replace batteries, reposition electrodes or replace deteriorating electrical leads. To overcome these drawbacks, engineers are now designing electronics that can process complex neurological signals to treat brain disorders while conforming to its soft tissue. Malliaras said that means developing electronics capable of interacting with the diverse chemicals the brain uses to bridge the tiny gaps between neurons, called synapses, in order to transmit the neurochemical impulses that give rise to thinking and behavior. Mixed Conductors Form Key Connection Between Electronics and Brain Mixed conductors, materials that can transmit brain signals both ionically and electrically, promise to form this key connection by enabling the development of high-resolution cortical electrodes that monitor neurons without penetrating the brain. They’re also a springboard to the development of flexible pin-sized electronic devices that make neurosurgery much less invasive. That brings new hope for more effective treatments of neurological disorders like epilepsy. Traditionally, the first line of defense against seizures has been antiepileptic drugs, an ineffective treatment since 30% of patients are resistant to the medications, Malliaras said. Another drawback are side effects that include short-term memory loss, fatigue, blurred vision, speech impairments dizziness, nausea and weight loss. Resective surgery – disconnecting the diseased portion of the brain that causes seizures – is often the next option, but is not possible in cases when the procedure would risk damaging circuitry that controls cognition and behavior. Flexible Substrates Fuel Development of Tiny, Expandable Bioelectronics Devices With recent advances, studies on lab rats show that the miniature electrodes designed using flexible substrates made possible by photolithography can conform to the brain’s curvatures and creases to measure the slight electrical signals emitted by individual neurons without penetrating brain tissue and deliver drugs to prevent seizures in animals. Measuring just micrometers in width, these horseshoe-shaped microfluidic devices can pump GABA, a natural neurotransmitter that acts as a brake against neuronal excitability throughout the nervous system, through their minute perforations into the ion exchange membrane of the brain to prevent epileptic seizures. “The data from the research is very exciting, but the path to the clinic is long,” Malliaras said. Still, the findings are a step forward in better understanding the brain and treating its pathologies. Today, microfluidic devices are under development to localize drug delivery in order to bypass the blood-brain barrier and destroy remaining brain cancer cells after a tumor is removed. The devices promise not only to improve cancer treatment since a broad array of cancer drugs can’t cross the protective barrier, but to enable doctors to administer cancer-fighting drugs in smaller doses to help reduce side effects. Implantable electronics today are used to bring relief to sufferers of chronic pain. However, the sizeable paddle-type electrodes involve invasive surgery under general anesthesia and a hospital stay of a few days. An alternative is to implant smaller flexible devices through an outpatient spinal tap with local anesthesia, an approach with its own disadvantages. The devices are less efficient than paddles in delivering electrical stimulation and tend to shift position as the body moves, so are seen as an unreliable solution. That leaves patients to choose between an effective treatment requiring invasive surgery and a less intrusive but less effective alternative. One promising solution combines bioelectronics with soft robotics to enable expandable implants containing microfluidic channels that can be activated mechanically. The device’s malleable paddle electrode can be rolled up inside a needle, inserted with a final tap and then pneumatically unrolled for treatment. While the device so far has been tested only on human cadavers, it could spur the design of a broader category of expandable microfluidics devices that minimize the invasiveness of neurosurgery and get patients back on their feet sooner. The tiny flexible electronics could be available to veterinarians to treat dogs in as soon as next year, Malliaras said, and “hopefully someday in the not-to-distant future they’ll be used to treat human patients.” Michael Hall is a marketing communications manager at SEMI.

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.

COVID-19 has had an impact on the entire healthcare market. During the peak of the first wave, companies from the industrial and automotive sectors worked on repurposing their sensors and production lines to provide pressure sensors for respirators and temperature sensors for thermometers. At the same time, companies making sensors for wearables and other mobile devices used for remote monitoring of patients experienced saw increased demand, caused in part by the surge in telemedicine worldwide. In addition, strong demand for COVID-19 tests pushed diagnostic players to repurpose existing systems to detect the SARS-CoV-2 virus or associated antibodies. Over the past six months in particular, numerous microfluidic technologies have enabled either rapid point-of-care tests or high-throughput solutions for central labs. The demand for these tests is incredibly high (millions of tests per month are needed), which has contributed to boosting the revenue of many companies in the respiratory-testing area.These respiratory-testing companies have placed many testing machines at existing and new customer sites, and have sold an impressive number of test kits resulting in an initial revenue spike in Q1 2020, and even higher spikes in Q2 and Q3. This growth seems on track to last into early 2021 and beyond as the pandemic continues, the flu season arrives, and health organizations test increasingly higher numbers of people than they were several months ago. The winners in respiratory testing include Abbott, bioMérieux, Cepheid, GenMark and Luminex, among many others. In this context, Yole expects the point-of-care segment of the microfluidic product market to enjoy an impressive jump from US$4.5 billion in 2019 to US$6.3 billion in 2020, growing at 15.1% CAGR between 2019 and 2025 to reach $10.4 billion in 2025. This represents 40% of the total microfluidic product market in 2019.In its research on microfluidics, Yole tracks a wide range of COVID-19 tests from different companies. The tests are used to meet different needs. Evolution of COVID-19 TestingNo doubt this increased production of tests will be especially useful for the upcoming flu season. But what will happen next year, if (we hope) reliable COVID-19 vaccines are validated and marketed, and the new coronavirus eventually disappears? Will diagnostic companies’ sales fall to pre-pandemic levels, and all these investments in production lines be wasted? Don’t worry. This is not a one-shot deal: Once the pandemic is over, most testing machines will remain in place, and customers will use them to run other tests the companies offer – usually for other kind of infectious diseases – driving sales of single-use disposables in coming years. The pandemic has shown us that more efficient diagnostic tools are required. Rapid, inexpensive, widely accessible testing for infectious diseases is crucial if we are to face such challenging situations. The real struggle for diagnostic companies, especially in the field of microfluidics where recent platforms have a small assay menu, is placing instruments (i.e., the test machines that run the disposable cartridges and read the results) at customers’ locations, from hospital settings and urgent care to field testing sites, and this has now been achieved. This will drive consumables sales in the future, even beyond the pandemic, and take the microfluidic-based point-of-care testing market to the next level. Rapid point-of-care testing is driving growth in microfluidics and will continue to do so for years to come. In the meantime, new significant opportunities are opening for point-of-care diagnostic test-makers, and rapid, miniaturized microfluidic technologies may be the winners here. Rapid passenger screening in airports, and rapid employee or visitor screening at the workplace will become essential for preventing the virus’ spread. In total, this could represent billions of rapid tests needed per year. COVID-19 has slowed down business growth in many areas but has really helped microfluidic-based point-of-care diagnostics take it to the next level, and this is only the beginning.For more information on Yole’s microfluidics activities, please view Yole’s reports, Point of Need 2020 – Including PCR-Based Testing or Status of Microfluidics Industry 2020 or visit i-Micronews.comYole Développement is a member of SEMI and the MEMS Sensors Industry Group (MSIG), a SEMI technology community that connects the MEMS and sensors supply network in established and emerging markets enabling members to grow and prosper. Visit us today. Sébastien Clerc is a technology and market analyst in Microfluidics, Sensing Actuating at Yole Développement (Yole). As part of the Photonics Sensing team, Clerc has authored a collection of market and technology reports dedicated to microfluidics and other micro-devices for major market segments: medical (including diagnostics, pharmaceutical, biotechnology, drug delivery, medical devices) and industrial (including environment, agro-food). At the same time, he is involved in custom projects such as strategic marketing, technology scouting, and technology evaluation to help academic and industrial players in their innovation processes. Thanks to his technology and market expertise, Clerc has spoken in more than 20 industry conferences worldwide over the last four years. Clerc holds a master’s degree in Biomedical Technologies and a master’s degree in Innovation and Technology Management, both from Grenoble Institute of Technology (Grenoble INP - Grenoble, France).

As the world confronts the health crisis of a generation in the form of the fast-spreading coronavirus, the microelectronics industry remains firmly in the spotlight. Aware of the central role they play in the fight against the COVID-19 pandemic, a growing number of companies are joining efforts to combat the virus by developing technologies for coronavirus detection, contact tracing and predicting its spread.SkyWater Technology, a U.S.-based foundry and prestigious member of SEMI-Fab Owners Alliance, is on the front lines in supplying an essential microfluidic MEMS component used in COVID-19 testing and research to identify mutations of the virus. This component is instrumental for the sequencing kit in the DNBSEQ-T7 system, an ultra-high-throughput sequencing system manufactured by MGI, a subsidiary of global genomics leader BGI Group.SEMI had the pleasure to catch up with Thomas Sonderman, president of SkyWater Technology, to talk about the company’s valuable contribution to the detection of COVID-19. He also gave us a peek into its business continuity plan and the safety measures it is taking to resiliently run a 24/7 chip-making operation amid these unprecedented times.SEMI: Tell us about SkyWater's contribution to the detection of COVID-19 and your partnership with MGI?Sonderman: SkyWater has been working with genomics sequencing leader MGI for several years to supply a critical component used in MGI's DNBSEQ-T7, an ultra-high-throughput sequencing system. The component we supply to MGI is a microfluidic MEMS device that uses microscopic channels to help perform very small-scale chemical reactions in the genetic sequencing platform. MGI's DNBSEQ-T7 identifies and monitors possible mutations of viruses, which is important for epidemiologists when tracking how viral illnesses such as COVID-19 spread through human populations.MGI’s sequencing system is used in parallel with its sister company BGI Genomics’ RT-PCR test kit, which is typically used more broadly as an initial screening agent due to its ability to return virus detection results within a matter of hours. Sequencing with the DNBSEQ-T7 can be used to confirm results of the RT-PCR tests that have indicated positive for the presence of the virus and then to perform a full DNA sequence of these positive specimens, which can help track mutations in the virus.DNBSEQ-T7 is important in the fight against COVID-19 as it tracks how the virus changes and enables scientists to look at its genetic sequence like a fingerprint at a crime scene. Their focus is on finding sudden changes in the sequence over time — a mutation. When they analyze available genomes from infected patients in several countries, they can see if inevitable virus mutations are causing associated illnesses that may have different incubation periods, contagiousness or deadliness – all critical dynamics that must be tracked by public health officials during an outbreak such as this.SEMI: What was the path that brought your company to the forefront of this testing?Sonderman: MGI’s DNBSEQ-T7 sequencing system and BGI’s RT-PCR rapid testing kit were among the first officially approved products by the National Medical Products Administration (NMPA – essentially China’s version of the FDA) – to fight the outbreak. MGI’s manufacturing plant, based in Wuhan, was able to fast-track its response, producing and delivering test kits very quickly to many hospitals and disease control centers in Wuhan and other cities in China.As concerns continue to rise about COVID-19 and we strive to flatten the curve, the pressure is on to enable even faster, more accessible testing. On March 27th, BGI’s RT-PCR virus detection test received FDA Emergency Use Authorization (EUA) for use in the U.S. The test works in just three hours. MGI’s DNBSEQ™ T7 sequencers are being used in China and other countries now and will be available in the U.S. starting in Q3. Products from BGI/MGI and affiliates are currently being distributed to more than 70 countries and regions worldwide to assist the global efforts in fighting the pandemic.SkyWater is certified to the ISO 13485 Quality Standard for Medical Devices to support the design, development and fabrication of DNA sequencing and other biochip applications in a wide range of emerging biomedical market segments. This allows us to provide this type of cutting-edge technology solution that is making an important contribution to coronavirus detection.SEMI: Given the challenges COVID-19 has placed on workforce and supply chain, what steps are being taken by your company to mitigate disruptions? Sonderman: SkyWater has been identified as Essential Critical Infrastructure per the U.S. Dept. of Homeland Security in several categories including Healthcare/Public Health Sector, Defense Industrial Base Sector, Information Technology Sector, and Critical Manufacturing Sector. To maintain continuity of operations, we contacted our close market partners as we need their support to continue supply of their starting and manufacturing support materials necessary for us to maintain operations. We asked these organizations to make every reasonable effort to fulfill our order requirements while also following recommended protective measures and are actively monitoring these relationships for possible developments that could be disruptive. By means of their partnership with us, these suppliers, too, are a part of the Essential Critical Infrastructure. Currently, there has been no change in wafer operations or fab utilization during this time of COVID-19.In addition to our sustained operations, our fab expansion is well underway as construction continues. The over 60,000-square-foot facility expansion adds clean room area and infrastructure to support the Department of Defense’s investment in SkyWater to broaden our production capabilities for Strategic Rad-Hard electronics and other complementary technologies. A fab technician in SkyWater’s SkyTech Center, an expansion of its operations to enhance advanced processing capabilities at its U.S.-based and U.S.-owned manufacturing facility. SEMI: What advice would you give to other companies seeking to keep their operations running amid COVID-19?Sonderman: First and foremost, creating a Pandemic Response Team (PRT) was critical for us in planning how to operate and communicate during this crisis. Our PRT updates our leadership team multiple times per week to enact procedures and ensure alignment throughout the organization. We follow CDC alerts and other local, state, and federal government guidelines on how to deal with home and work environments while communicating with all company stakeholders. This is important in providing reassurance of the company’s continued business and details on any potential change in operations.Increasing the frequency of communication with the organization’s supply chain to anticipate any disruptions in service is vital. Also, keeping in contact with customers is imperative to take the pulse of their continued operations during COVID-19. We recommend being flexible and pursuing new paradigms in getting business accomplished, such as telecommuting. In addition, if a company is deemed an essential business, we suggest drafting a letter in advance for employees should they need to prove why they are in transit (to and from work) if transportation becomes severely limited and monitored.Communicating with employees on how operations are changing is crucial. Ensure there is an intranet site that employees can access remotely via laptops or mobile devices that allows for ongoing updates and a way to communicate to all employees as things continue to evolve.We also put several safety measures in place, including: A screening process was set up to take the temperature of everyone entering the building. Site access is restricted for vendors, contractors, customers and other visitors as a default policy. Employee travel is restricted. All employees who can do their jobs from home can stay home. For essential on-site workers, we allow flexible schedules so people can move shifts if needed. Shifts have been staggered so people are not congested at lockers, gowning areas and other places. Physical distancing is required everywhere inside and outside the building. Video conferencing is being used even for participants inside the building. The number of people allowed in conference rooms is limited to comply with physical distancing; some chairs were removed and maximum occupancy signs were posted. Hand-sanitizing stations have been set up. We are providing employees access to masks, gloves and cleaning wipes. Safety measures are posted around the building and cleaning frequency of hard surfaces has been ramped significantly. These safety measures are among several other modifications we’ve made to daily operating procedures. SEMI: Please share some examples of how the SEMI Fab Owners Alliance (FOA) has helped support your business?Sonderman: Our Pandemic Response Team has leveraged the FOA recently by participating in its webinars on COVID-19 to ensure we are using industry best practices. We also use FOA surveys to provide and request information pertaining to COVID-19 practices.We have implemented building entrance protocols (i.e. temperature scanning, restricting access for non-employees) and expanded building cleaning procedures, including increasing the cleaning frequency of specific high-touch items. We have adjusted shift start times to minimize the number of personnel in the change room at the same time and we store each fab worker’s hood in the sleeve of the suit. These last two items resulted from a conversation with another FOA member.Outside of the pandemic, we have leveraged the FOA by participating in its industry-wide maintenance best practices and learning group that meets monthly on maintenance needs, issues and concerns within the industry. This allows us to learn from each other within the semiconductor industry. We have also leveraged this group in sourcing parts and/or parts sharing on tools no longer supported by OEMs.We greatly value the type of cross-organizational sharing and learning the FOA facilitates. It has been beneficial in a number of ways over the years. At this time, the FOA is especially useful when best practices are crucial to enable us and our peers to minimize disruptions, operate with the utmost safety, and quickly adapt to this new environment.SkyWater is a member of the SEMI Fab Owners Alliance, an international group of semiconductor and MEMS fab managers and industry suppliers that meets regularly to solve common non-competitive manufacturing issues and improve their business results. Nishita Rao is a product marketing manager at SEMI.

On Saturday, March, 21, 2020 the U.S. Food and Drug Administration (FDA) gave emergency authorization to Cepheid, a California company, to sell a new test for rapid detection of the pandemic coronavirus SARS-CoV-2, which causes COVID-19. Cepheid’s Xpert® Xpress SARS-CoV-2 test gives healthcare workers results in just 45 minutes, with less than a minute of hands-on time for sample preparation.Cepheid, founded by Kurt Petersen, M. Allen Northrup and five others in 1996, is well known in the MEMS community for commercializing microfluidic chip-based polymerase chain reaction (PCR) analysis machines. This is not the first time Cepheid has responded quickly to a biological threat; after the 2001 terrorist attacks in the USA, Cepheid was the first to provide rapid anthrax detection capabilities to the U.S. Postal Service, and it still does today.At the heart of all COVID-19 test protocols (see the WHO protocol and U.S. CDC protocol) is the real-time reverse transcription polymerase chain reaction (RT-PCR) analysis technique. In a very simplified description, PCR uses thermal cycling to amplify the DNA present in a patient’s swab sample, and then using fluorescence optical detection, searches for the virus’s specific DNA. The test requires knowing the virus’s genome in the first place; the crucial work to sequence the full genome of SARS-CoV-2 was first published by Chinese scientists for public use on January 10, 2020.While traditional PCR machines take many hours to thermal cycle and reach a result, MEMS-based PCR systems can work much faster. Featuring scale heaters and reaction chambers that have a tiny thermal mass, they create a significantly faster heat-cool cycle, enabling a rapid result in minutes.The first MEMS silicon PCR chip, developed by Northrup et. al. at Lawrence Livermore National Laboratory and licensed to Cepheid (left) and the Cepheid test cartridge today (right). (Source: Northrup MA, Ching MT, White RM, Watson RT, “DNA amplification in a microfabricated reaction chamber,” Transducers 1993, Yokohama, Japan. pp. 924–926.) Research on MEMS-based PCR systems has continued steadily since the early 1990s. Today, researchers have been focusing on developing highly integrated, low-cost systems specifically for point-of-care use. One example of recent research: a team at Korea’s ETRI and Genesystem have developed a prototype low-cost, handheld PCR system having a polyimide chamber and microheater and an integrated CMOS detector for optical readout of results (figure below). Cross-section schematic of the chamber, heating module and integrated optical detector in a portable PCR prototype (left) and integrated test cartridge (right). (Source: DS Lee, OR Choi, and YJ Seo, “A Handheld and Battery-Powered Realtime Microfluidic PCR Amplification Device,” Transducers 2019, Berlin, Germany pp. 1063-1065.) Korea’s quick recruitment of its biotech companies and creation of novel drive-through testing sites helped it to successfully pinpoint its COVID-19 outbreak and to implement control measures. Let’s hope the Cepheid test can be similarly effective.Based on successive epidemics of SARS, MERS and now COVID-19, rapid PCR test machines, enabled by MEMS technology, are becoming essential medical tools in the fight against viral outbreaks. As continued development lowers the cost of such critical equipment, let’s hope we may soon have a PCR machine in every doctor’s office.Alissa M. Fitzgerald, Ph.D., founded A.M. Fitzgerald Associates, LLC (“AMFitzgerald”), a MEMS and sensors solutions company based in Burlingame, CA, in 2003. She has over 25 years of engineering experience in MEMS design, fabrication and product development.Prior to founding AMFitzgerald, Fitzgerald worked at the Jet Propulsion Laboratory, Orbital Sciences Corporation, Sigpro, and Sensant Corporation, now part of Siemens. She received her bachelor’s and master’s degrees from MIT and her doctorate from Stanford University, in Aeronautics and Astronautics. Fitzgerald has numerous journal publications and holds eight patents. She served on the Governing Council of MEMS Industry Group from 2008-2014 and was inducted into the MIG Hall of Fame in 2013. Fitzgerald serves on the Board of Directors of both Rigetti Computing and the Transducer Research Foundation.AMFitzgerald is a longtime member of MEMS Sensors Industry Group (MSIG), a SEMI Strategic Association Partner. For more information on AMFitzgerald, please visit: https://www.amfitzgerald.com.Interested in learning more about this topic? Read Alissa M. Fitzgerald and Farzad Khademolhosseini’s article in EE Times, MEMS in the Fight Against Covid-19.

MEMS technology has changed human interaction with electronic devices. Introduced in the 1990s, the first mass-market MEMS devices were used for inkjet printheads and automotive airbag crash sensors. Today, MEMS are ubiquitous, with billions of the tiny devices adding intelligence and interactivity to smartphones, smart speakers, wearables, automobiles, biomedical devices, remote monitoring and event detection systems, and countless other applications. Integrating MEMS with Flexible Hybrid Electronics (FHE) is an important step in the evolution of this miniaturized intelligent sensing technology, paving the way for its use in new classes of flexible, conformal devices.The integration of the two technologies promises to breed new applications in small form factors but also presents challenges inherent to FHE design and fabrication processes. SEMI’s Nishita Rao caught up with Nathan Pretorius, prototyping and automation engineer, NextFlex, to discuss MEMS-FHE device integration challenges and opportunities ahead of his February 26 presentation, Integrating MEMS Devices in FHE, at FLEX|MEMS Sensors Technical Congress (MSTC) 2020, February 24-27, 2020, at the DoubleTree by Hilton in San Jose, California.Join us at FLEX|MSTC to meet Nathan and other industry influencers advancing innovation in FHE and MEMS sensors. Register now to connect with him at FLEX|MSTC or visit him on LinkedIn.SEMI: Why is integrating MEMS devices into FHE systems important? What new use cases might it enable?Pretorius: The main value proposition of integrating MEMS devices into FHE is that it allows MEMS devices to exist in a different form factor than was possible previously, giving us high-quality MEMS sensors on the flexible and conformable platform of FHE.Ease of application, flexibility, lower cost and rapid iteration on a design are just some of the benefits of FHE devices. And because there are few robust FHE sensors that overlap with MEMS’ capabilities, when you combine the two, you get a lot of compelling uses. That’s why NextFlex is working with agencies and companies to evaluate MEMS’ integration, including using bare MEMS die with microfluidics and promoting new ways of attaching and packaging MEMS die for use with FHE. SEMI: Why is FHE an ideal platform for integrating various types of sensors?Pretorius: MEMS integrated with FHE devices are ideal for rapid design and deployment of data-gathering sensor nodes — which we can iterate for specific applications. A few examples include on-body health monitoring devices for bio-fluids analysis, medical pressure sensors for monitoring blood pressure, and peel-and-stick sensors nodes for infrastructure monitoring. In terms of design and production, FHE devices support rapid prototyping, allowing for instantaneous design-iteration cycles. This speeds design-to-production over traditional rigid PCBs and copper flex because the feedback cycle time between design, manufacturing and testing is shorter, accelerating time to market. What’s exciting about FHE technology is that a variety of sensors or components, including MEMS, can be designed into the base system to easily customize it for a specific application. In addition, our experience shows that when compared to a traditional rigid PCB, an FHE board reduces manufacturing steps and device weight by two-thirds and, perhaps most importantly, converts the device to a thin, conformal shape that makes possible products in new form factors. SEMI: What are the primary challenges to integrating MEMS with FHE? What is NextFlex doing to help device manufacturers address these challenges? Pretorius: There are a few challenges, some of which are device-specific. Most recently, I’ve been focusing on inertial and timing devices, including accelerometers, gyroscopes and resonators. There are a few technical challenges involved in the process of getting the devices from the wafer to an FHE substrate. The wafer processing is very important, especially the dicing and thinning steps. After thinning and dicing, the die is placed onto the FHE substrate. The stresses caused by bonding to the substrate have to be understood and characterized. After placing the die, you then have a calibration step, which is normally performed after the device is packaged. With a MEMS die placed onto directly onto an FHE substrate, calibration then must be done.Finally, the device encapsulation is important, since on an FHE substrate the hard-to-soft material transition is very important to mitigate stresses to rigid component interfaces. We have also been looking at how to work with devices that have damping vents. Flexible encapsulants are inherently more permeable to gases and water vapor than hard encapsulants, so studying the encapsulation of MEMS devices on FHE is another area of interest. NextFlex has been working in a supporting role to evaluate best design practices and best attach and integration methods. In addition to our ongoing collaborative programs, NextFlex is developing the FHE manufacturing ecosystem to include system and component manufacturers and designers, product developers, and materials and equipment providers.SEMI: How do we facilitate closer collaboration between the FHE manufacturing ecosystem and MEMS suppliers such as MEMS device manufacturers, product developers, and materials and equipment providers?Pretorius: It’s important to include manufacturers early in the design process so we can identify challenges up front. That’s why NextFlex spearheads technology road-mapping efforts that include representatives from across the manufacturing ecosystem. We use the roadmaps to prioritize challenges that we can address effectively through collaboration, focusing the industry on solving problems through Project Calls that reveal integration challenges and results from real devices and that tell us how the materials and equipment actually perform with a real device.NextFlex keeps the information flowing, holding quarterly project update webinars to share results. As current devices are optimized for the process in which they will be used, we learn a lot from the project performers who make FHE system demonstrators — and we share that information with the member community. SEMI: Can you point to an example of a successful MEMS-FHE device integration?Pretorius: MEMS-FHE integration is still in the early stages, but we are working on several projects including a DARPA Seedling project for which we have integrated MEMS sensors into FHE systems for testing and evaluation. We plan to continue this work by integrating MEMS and FHE devices using methods that support mass production.SEMI: What would you like FLEX|MSTC attendees to take away from your presentation?Pretorius: We would like to see the FHE community work more closely with MEMS device manufacturers. For example, NextFlex often works with manufacturers to gain access to bare die, which is still a significant hurdle in making devices.The best way to speed things along is to get involved. We encourage FLEX|MSTC attendees to join NextFlex. As a prototyping and automation engineer at NextFlex, Nathan Pretorius explores new print methods for prototyping and automation using novel materials and processes. Pretorius currently focuses on how best to apply software scripting and machine learning to streamline FHE processes. Prior to joining NextFlex, he researched the strengths of roll to roll and screen printing on printed electronics designs, including capacitive touch interfaces, FHE passive component design, and antennas. Nathan holds a Bachelor of Science degree in Graphic Communications from Clemson University. 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.Nishita Rao is marketing manager for technology communities at SEMI.

The BioMEMS market is becoming increasingly diverse, encompassing gas and pressure sensors, ultrasound, specialized biomedical sensors, and other types of MEMS and microfluidic chips used for drug delivery and analytical applications. The BioMEMS market is also growing steadily: Research firm Yole Développement predicts that BioMEMS will grow at 14.9% CAGR from 2017-2023, reaching US$6.9B by 2023.1 As a high-value market, BioMEMS is worth pursuing as long as you can manage the complexities of manufacturing, including a sometimes-fragmented supply chain. Fortunately, the MEMS manufacturing ecosystem is evolving to accommodate the needs of companies that are in the process of commercializing BioMEMS-enabled products. Understanding the ecosystem’s shifting dynamics will help BioMEMS to flourish in this promising while often-challenging market segment.Unique Product, Unique ProcessIn the world of semiconductor manufacturing, it is routine for a fab to manufacture hundreds of different device designs using just a handful of process nodes. Semiconductor foundries share their design rules with customers, who then develop the mask set accordingly, literally adapting their designs to fit the rules for manufacturing on one of the foundries’ process nodes. In stark contrast, most MEMS devices cannot conform to the level of standardized manufacturing processes that work so well for semiconductors. Rather, MEMS challenges us to develop individualized processes for each device. It’s one product, one process.New BioMEMS designs generally emerge from either corporate R D or academia, two groups that approach specialized MEMS foundries such as ours when they’re entering pilot or low-volume production. Today successful commercialization depends on open, accurate communication and close collaboration. MEMS foundries must work side-by-side with designers to ensure that designs are based on real-world manufacturing process technologies. This highly customized manufacturing model makes it very difficult to support future demand for the groundswell of diverse BioMEMS devices that are in development. If we want to handle this upward trajectory of BioMEMS, we’ll need to adapt.Change the ModelWhile most existing MEMS foundries currently support a wide variety of devices types, I predict that market forces will cause our foundries to move toward specialization. Some companies will specialize in what they already do best, e.g., inertial sensors for the automotive industry. Others might choose to develop their foundry business around a purpose-built facility, which, for example, only manufactures microfluidics or magnetic devices. Larger enterprises might opt to build captive foundries that are designed to serve their specific needs. Get Creative: Combine, CollaborateSatisfying the thriving market for BioMEMS will require creativity. One idea: combine different disciplines of the manufacturing process at the same foundry. For example, we could have a biochemistry fab and a MEMS fab under the same roof, or we could have a MEMS fab and a packaging facility in one building. While these approaches may not yet exist outside of academia, necessity may drive them to fruition.It will also require heightened strategic collaboration, a process that has already begun. To support both large volumes and greater diversity of devices, some MEMS foundries are building cooperative relationships with former competitors. Think of it as a restructuring of the supply chain.Embracing the special challenges of BioMEMS manufacturing is worth our investment in time and resources. We need to step back, individually and collectively, to understand where each of the existing MEMS foundries fits into the new supply chain so we can leverage our strengths. We can start by forging stronger alliances for tech transfer. Once we more freely share information as we engage in joint product development — involving technology teams who are more connected and less guarded — we will expedite tech transfer and manufacturability.While we are unlikely to achieve the same level of standardization that has enabled the semiconductor industry to reach its great heights, as long as we evolve to meet demand, we will grow together and prosper.To learn more about this topic, meet with Jessica Gomez at the upcoming SEMI-MSIG MEMS Sensors Executive Congress (October 22-24, 2019 in Coronado, Calif.) or email her: [email protected][1] “BioMEMS Emerging Non-Invasive Biosensors: Microsystems for Life Sciences Healthcare 2018 Report,” Yole Développement, https://yole-i-micronews-com.osu.eu-west-2.outscale.com/uploads/2018/08/Sample-BioMEMS-Non-Invasive-Sensors-Microsystems-for-Life-Sciences-Healthcare-2018-.pdf As founder and CEO of Rogue Valley Microdevices, Jessica Gomez has created a world-class precision MEMS foundry and wafer fab in the heart of Southern Oregon. Integral to her role as CEO, Ms. Gomez practices a business philosophy of offering custom design, best-in-class process technology and R D expertise to customers, to help them achieve the highest quality and reliability in their products.In 2018, Ms. Gomez was selected for the prestigious SEMI Board of Industry Leaders. SEMI also recognized her in its first Spotlight on SEMI Women, which honors accomplished women in the global microelectronics industry.Prior to founding Rogue Valley Microdevices in 2003, Ms. Gomez honed her experience in semiconductor processing and production management through positions at Standard Microsystems Corporation, Integrated Micromachines and Xponent Photonics.For more information, visit: https://roguevalleymicrodevices.com/Rogue Valley Microdevices is a longtime member and supporter of SEMI-MEMS Sensors Industry Group, which connects the MEMS and sensors supply network, allowing members to address common industry challenges and explore new markets.

Despite market saturation and stagnation saddling many business sectors, MEMS remains a shining star in the semiconductor industry. Opportunities in automotive, consumer electronics, mobile, medical are rising. What is supporting this industry growth? Who are the big players on the horizon?SEMI spoke with Dimitrios Damianos, Technology Market Analyst, Photonics, Sensing and Display division at Yole Développement, about MEMS market dynamics and future trends. Damianos shared his views ahead of his presentation at SEMI MEMS Imaging Sensors Summit, 25-27 September, 2019, at the WTC in Grenoble, France. Join us at the event to meet experts from Yole and many other key industry influencers. Registration is open.SEMI: MEMS and sensors is one of the healthiest industries not only in Europe but globally. Despite a global economic slowdown, the MEMS and sensors is still growing. What is fueling this growth?Damianos: The value of the global MEMS and sensor market will almost double from $48 billion in 2018 to $93 billion in 2024. In 2018 the MEMS and sensor market represented more than 10% of the total IC market, as more and more MEMS devices and sensors, such as MEMS, image sensors, and RF filters, are integrated in end products in consumer and automotive. In particular, the value of the MEMS-only market reached $11.6 billion in 2018, with consumer applications accounting for more than 60% of the total market. From 2019 to 2024 the MEMS market will grow 8.3% annually in value driven by pressure (for TPMS), RF (for V2X 5G communications), inertial (for ADAS) and future MEMS (such as pMUT for ultrasonic fingerprint) (Source: Status of the MEMS Industry report, Yole Développement, 2019). SEMI: How are MEMS shaping the semiconductor industry today? Damianos: MEMS have a make-smarter enabling capability. They are providing context for new applications and services in transportation, mobility, health, and security. Large companies such as Alibaba and Google are considering MEMS as a critical element in their business solution domains covering the upcoming smart home, smart campus, smart city and smart industry applications. MEMS have key features that correspond to these companies’ criteria for accuracy, small size (without performance degradation), low power and always on (e.g. microphones). Furthermore, with the advent of sensor fusion and edge computing, more sensor data can be processed, maximizing the qualitative and useful information about us and our surroundings. This has a huge impact in all markets, especially consumer.SEMI: MEMS foundries performed well thanks to the boom in industrial and medical applications. Who are the big players right now?Damianos: During 2018, all foundries saw their revenue increase. STMicroelectronics, Teledyne Dalsa, Silex, IMT, Micralyne and Philips Innovation Service are important MEMS foundry players that offer services for various MEMS devices used in medical and industrial markets, among others. On one hand, medical applications were driven mostly by microfluidics, flowmeters, pressure and inertial MEMS. On the other hand, industrial applications were driven by inkjet heads, microbolometers and pressure MEMS. The market prospect, however, is huge for RF MEMS and oscillators that will be used in next-generation 5G infrastructure. SEMI: What is the current status of MEMS for automotive applications? What are the related market drivers? Damianos: In automotive applications, accelerometers and pressure sensors still account for the lion’s share in units. Pressure sensors will grow at more than 8% with Tire Pressure Monitoring System (TPMS) implemented in Chinese vehicles in the near future. After 2019 and 2020, with the new Chinese standard, GB 2614, TPMS will become compulsory: 100% of all new vehicles will have TPMS. Also, automotive MEMS could grow quicker than the corresponding car market (currently at approximately 3%). The reason is a higher number of many different MEMS devices that are being integrated in cars, such as MEMS inertial measurement units (IMUs), TPMS, environmental MEMS for gas and particle monitoring in-cabin and microphones for hands-free voice commands.SEMI: After years of decline, the inkjet heads industry is growing again. What other segments are benefiting from MEMS technology applications? Can you name two examples?Damianos: RF MEMS (BAW filters) is also benefiting from applications in smartphones and will continue to benefit with the arrival of 5G. 5G means additional high frequency sub-6 GHz bands that can only be addressed by BAW filters. Moreover, new infrastructure approach using active antennas will create an expanding market for BAW.Another segment is inertial sensors. Inertial MEMS already have a high potential in wellness and fitness wearables and are gaining support for medical wearable applications to monitor patient activity, with the aim to prevent seizure in cases of epilepsy and other mental disorders. Compared to other types of sensors, MEMS is the golden technology for inertial sensors integrated into medical wearables. They are used for rehabilitation systems, activity trackers and assistance living/fall detection. Specifically, the IMU market will continue to grow for consumer and automotive applications as their price and form factor continue to shrink and they replace traditional standalone MEMS accelerometers and gyroscopes. However, the inertial sensor market will mostly grow for smartphone applications (mostly 6DOF, with 9DOF volumes being comparatively low).SEMI: Give us one prediction about the opportunities offered by the MEMS technology. Damianos: Sensor fusion is becoming more and more relevant since billions of MEMS sensors are made every year. The upcoming 5G revolution will make connectivity easier than ever, creating exponentially more data. To make these data meaningful, data processing is mandatory. Big data is an industry born of recent advancements in AI and machine learning, built upon and fueled by a wealth of new data from ever-expanding sensor applications. An upcoming trend is edge computing, with sensors and MEMS driving a new age of technology. Sensors are digitizing the human experience, and as the real and virtual worlds move closer together, it will be sensors that bind them, enabling new experiences for users everywhere. Running AI at the edge, coupled with sensor fusion, will open new applications for MEMS in audio, motion, olfactometry, and imaging. We also expect that new MEMS devices (microspeakers, ultrasonic fingerprint, pMUT) and piezoelectric MEMS technology could rejuvenate the MEMS market. SEMI: What are your expectations for SEMI MEMS Imaging Sensors Summit and why would you invite your peers to attend? Damianos: SEMI is organizing another very successful event, gathering experts from the Imaging and MEMS industries. We are at a turning point of innovation, with many technological advancements in AI, IoT, AR/VR, biometrics, and other areas where Imaging and MEMS technologies are paramount. Yole is excited to hear the thoughts of many high-profile experts on existing activities and future prospects within their organizations. If you are too, then it is an event that you shouldn’t miss!Dimitrios Damianos, Ph.D. is a Technology and Market Analyst in the Photonics, Sensing and Display division at Yole Développement (Yole). Damianos is a member of a Yole team that produces technology and market reports on the imaging industry including photonics and sensors. Damianos holds a MSc degree in Photonics from the University of Patras (Greece). After his research on theoretical and experimental quantum optics and laser light generation, Dimitrios pursued a Ph.D. in optical and electrical characterization of dielectric materials on silicon with applications in photovoltaics and image sensors, as well as SOI for microelectronics at Grenoble’s university (France). He has also authored and co-authored several scientific papers in international peer-reviewed journals. Learn more! Join the webinar on 5th September 2019. Registration is open! Serena Brischetto is a marketing and communications manager at SEMI Europe.