Dr. Alissa M. Fitzgerald

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.

When developing industry forecasts, market analysts gather data from hundreds of companies to provide actionable insights on established technologies and to identify near-term business opportunities. As a developer of new MEMS and sensor technologies for a range of commercial applications, clients often ask us, “What’s going to be hot?” Gauging the promise of emerging technologies that are five to 10 years from commercialization requires taking a different tack.History tells us that most of today’s blockbuster MEMS products were born as academic research projects. Years of hard work by entrepreneurs, funded by millions of dollars, have turned proof-of-concept research into new commercial products. To identify up-and-coming technologies, we gather information straight from the source: academic conferences and articles.Chirp Microsystems is a good proof point of our research methodology: In my 2012 report on emerging technologies, I highlighted research from UC Berkeley and UC Davis on “In-Air Ultrasonic Rangefinding and Angle Estimation Using an Array of AlN Micromachined Transducers.” Soon after publication, the authors incorporated Chirp Microsystems to commercialize their technology for gesture- and fingerprint-recognition applications.After five years of development work, Chirp’s products are entering the marketplace. In February 2018, the global supplier TDK InvenSense acquired Chirp, underscoring the company’s commercial potential. At October’s SEMI-MSIG MEMS Sensors Executive Congress in Napa, Calif., Chirp’s CEO, Dr. Michelle Kiang, held attendees rapt as she described her company’s journey from startup to wholly owned subsidiary.There’s a methodThis year, I reviewed over 100 papers from top researchers presenting noteworthy technologies at the Hilton Head Workshop on Solid-State Sensors, Actuators and Microsystems. My criteria for selection were: commercial relevance; offers a solution to a known or anticipated problem; and technology game-changers. The following caught my eye: Event-driven sensors: Cleverly designed silicon MEMS that consume no power while standing by. A triggering mechanical or thermal event closes a contact within the sensor to activate its circuitry and telemetry. These sensors leverage existing fabrication methods, so they could become commercial products within five years for event monitoring and security applications. (UT Dallas, Northeastern University). Figure: 5-bit accelerometer having zero standby power. The device is open circuit until a threshold acceleration closes a mechanical contact. Source: University of Texas at Dallas. Thin film piezoelectric resonators: Advances in PZT deposition methods and process integration with CMOS were used to create monolithic acoustic waveguides for RF filtering in 5G applications. This new filter design, using existing scalable processes, is ripe for commercialization. (Purdue University, Texas Instruments) Intra-body communications: MEMS ultrasound transceivers, made from aluminum nitride, can send data directly through flesh at Mbit/s data rate. With trends toward networks of multiple implanted or wearable medical devices, this innovation would enable medically safe, secure, intra-body wireless communication. This early-stage work still needs in vivo validation and would likely require 10 or more years for development and regulatory approval. (Northeastern University) Screen- and 3D-printed sensors: One example of many exciting innovations using screen- and 3D-printing are potentiometric nitrate soil sensors. Low-cost and biodegradable, these sensors could be spread over huge areas to monitor a farm’s soil quality. Table-top and hobbyist tools are currently used to make screen- and 3D-printed devices, so new manufacturing equipment and infrastructure must be developed before commercial production could occur. (Purdue University) Biodegradable batteries: A paper-based battery that can deliver 0.5 uW of power, ingeniously using bacterial metabolism as the electrolyte. These batteries dissolve in water and could one day be used to power temporary medical implants or biodegradable sensors. This exciting proof-of-concept prototype will require significant process development and new manufacturing infrastructure for commercialization. (SUNY Binghamton) Figure: Paper-based battery dissolves in 60 minutes after immersion in water. Source: SUNY Binghamton To read more about these technologies, please download my presentation from SEMI-MSIG’s MEMS Sensors TechXpot at SEMICON West 2018.Alissa M. Fitzgerald, Ph.D., is the founder and managing member of A.M. Fitzgerald Associates, LLC, a MEMS and sensors development company in Burlingame, CA. She has over 20 years of engineering experience in MEMS design, fabrication and product development and now advises clients on the entire cycle of product development, from business and IP strategy to manufacturing operations. She is a frequent speaker at industry conferences and currently serves as a director of the Transducer Research Foundation, sponsor of the Hilton Head Workshop. She received her bachelor’s and master’s degrees from MIT and her doctorate from Stanford University in Aeronautics and Astronautics.For more information, visit: www.amfitzgerald.com