The COVID-19 pandemic has had a significant impact on every aspect of our lives. Almost every single person has been affected in some way – be it their health, their profession or their entire life. But there are also some rays of hope worth mentioning, among them the rapid development of vaccines, testing kits and, in the future, medications, all of which have contributed considerably to managing this crisis. “The pandemic has shown us the importance of cutting-edge, high-end technologies, as these enable us to pursue rapid and effective research and development activities, for example in the fields of medication, vaccines and diagnostic devices,” confirms Dr Thomas R. Dietrich, CEO of the IVAM Microtechnology Network. Microfluidic components are particularly well suited to significantly accelerate the pace of development, something that was impressively demonstrated at the COMPAMED Innovation Forum. Held in digital format on June 16, 2021, the forum and its expert keynotes revolved around the leading topic “Microfluidics in mobile diagnostics and the development and manufacture of pharmaceuticals and vaccines”.

The forum has been organized by Messe Düsseldorf in close cooperation with IVAM for many years and consistently provides an outlook on current topics a few months ahead of COMPAMED, the internationally leading trade fair for suppliers in the medical-technology industry, held in Düsseldorf, Germany (next date: November 15 – 18, 2021, concurrently with MEDICA 2021).

A large number of tests over an extremely short period of time

Microfluidic components allow us to quickly conduct a multitude of experiments using what is known as a high-throughput screening method. This enables users to realize a large number of tests over extremely short periods of time, for example to test the effectiveness of medications or vaccines on living cells. The speed and accuracy of the tests is achieved through microstructures, which give researchers far better control over physical and chemical parameters (e.g. temperature, pressure, response times). These tiny structures have an additional benefit, as they require a lower number of samples and ensure the economic use of reagents. In the last months, new products and medications have been developed over a very short period of time, something that would not have been possible without microfluidic elements. Devices and components such as lab-on-a-chip and mobile diagnostic devices and chemical microreactors already play an active part in the battle against the pandemic.

Optimization potential on the one hand – a key role on the other

In general, microfluidic platforms are well suited to swiftly develop and commercialize point of care testing (POCT). However, creating the “ideal” POC test is a great challenge: besides being affordable, sensitive, specific and user friendly, it also has to be quick, robust, should not require additional devices and be deliverable to end consumers. The tests employed during the pandemic have shown that the various methods have different limitations, and that there is need for improvement. PCR tests, for example, are more time-consuming and need to be evaluated in a laboratory, which makes this method expensive and limits throughput. Antigen tests, on the other hand, have a low sensitivity and sometimes provide false negative results. Antibody tests that detect whether the patient has already recovered from an infection also have limited sensitivity. “These limitations show that there is no silver bullet when it comes to testing,” states Dr Holger Becker, Chief Scientific Officer at microfluidic ChipShop. Nonetheless, the expert is convinced that POCT will receive a sustainable boost and that microfluidics will play a key role, especially in molecular testing.

Point-of-care testing: A key tool during the pandemic

In the uture, we can expect to see additional technologies emerge in the field of POCT, which will catch on more easily in light of the pandemic. These include direct imaging techniques, potentially combined with artificial intelligence (AI) or silicon-based sensors (e.g. silicon photonics). CRISPR diagnostics are a relatively new tool (CRISPR stands for “Clustered Regularly Interspaced Short Palindromic Repeats”) that is used to identify specific RNA sequences. When detecting RNA viruses, one usually only has relatively small bits of genetic material in which to detect a virus-specific genetic sequence. CRISPR diagnostics use a Cas enzyme and a fluorescently labelled reporter RNA molecule. If the sample contains the targeted RNA, the Cas enzyme begins cutting the RNA from both the target and the reporter molecule, thus releasing the colored label, which in turn allows it to be detected. In other words, this is an indirect form of detection that at the same time is extremely specific – a true benefit. “As a rule, we expect to see a rise in demand for POCT, which will become a key tool in dealing with pandemics,” says Holger Becker.

This will then benefit companies such as microLIQUID (from Spain), which specializes in customer-specific microfluidic applications and has expertise in every step of the supply chain, from product design and development to the introduction of new products and manufacturing. “A lot of the time, taking a prototype into mass production creates a decisive bottleneck,” explains Dr Luis Fernández, CTO of microLIQUID, touching on a key challenge for which solutions are needed.

Increasing cost pressure drives innovation in the fields of life sciences, biotechnology and analytics. Preparing samples, generating and processing increasingly larger amounts of data and increasingly shorter throughput times all lead to a constant miniaturization of key components in glass and plastic. Flow cells, biochips, lab-on-a-chip components, gratings, integrated electrodes and microchannels and cuvettes: many components in the fields of biophotonics and microfluidics exhibit functional layers at the micro- and nanoscale.

Swiss company IMT Microtechnologies considers itself the perfect partner for companies in which microfluidics, biotechnology and optics overlap and that require a multidisciplinary approach as well as a broad portfolio of processes. “Translating an assay to a microfluidic solution requires a thorough understanding of the analyte and the methods used to isolate and/or dock it onto a surface within the channel network. It also requires that we identify the appropriate transduction mechanisms as well as the necessary processes and materials,” says Dr Alexios Paul Tzannis, Business Development Manager at IMT, describing part of this complex task. Here, combining complex structures on and in glass wafers with novel surface chemistry solutions gives rise to innovative consumables for use in life science and diagnostics.

Liquid control at the nanoscale

French company Fluigent offers a wide range of solutions for use in micro- and nanofluidic applications, all of which aim at increasing control, automation, precision and user-friendliness. “Microfluidics are paving the way for point-of-care diagnostics. The focus here lies on precise, fast and portable instruments that put the skills of a medical laboratory in the hand of the user, right at the point of care, for example in operating theatres,” says Jaques Pechdimaljian, OEM Product Manager at Fluigent, explaining the company’s alignment. Simply put, Fluigent is geared towards liquid control down to the nanoscale. As devices that generate and regulate microprints are gaining in popularity, Fluigent sees its focal point and added value in the adaptation of subcomponents for POC devices. These include portable devices (battery-powered, compact and lightweight) and precision devices (flow stability, accuracy) as well as reliable systems (prevention of blockage, contamination, bubbles, etc.). The fields of application for devices like these far exceed the realm of medical technology (ambulant examination to detect blood clots in the operating theatre). Other fields of application include detecting contamination in food and beverage manufacturing and screening municipal water for heavy metals.

POC devices quantitatively measure coronavirus antibodies

The pandemic has also shown that, while mRNA vaccines can be developed and adapted quickly, their production and logistics are more challenging. Upscaling to the large quantities required took time; in addition, definite statements on how long the immunity guaranteed by the vaccines will last are lacking. It would therefore be extremely helpful if POC devices were able to quantitatively measure antibodies. The requirements would be high: just one drop of blood drawn from the patient’s fingertip would have to suffice; the results of the measurements would need to be available after a short period of time (less than 20 minutes). Measurements would have to be highly sensitive and specific; measurement data would need to be gathered and processed digitally. But how could solutions like these be realized, without unwieldy devices, at reasonable investment costs and with an acceptable energy and reagent consumption?

“To improve how we utilize the benefits of microfluidics at the POC, we need to employ lightweight, active fluidic components with smaller dimensions as well as batteries that supply power and small fluidic volumes that allow systems to save reagents,” explains Florian Siemenroth of Bartels Mikrotechnik. According to statements made by the company and its partners mementis, microfluidic ChipShop, Honeywell and Sensirion, “the pieces of the puzzle” needed to realize active microfluidic systems are already on the table; a number of standard components are available and could be integrated into an ultra compact and smart system. These include miniature valves, smart pumps and control units, flow sensors, test tubes and a tubing system. All these available components, and the systems they can be used to generate, exhibit the desired benefits: they allow the use of conventional components to automate fluidic processes; have a low electricity consumption and internal volume; the entire system is ultra compact and fits on a 96-well Microtiter plate (around 128 by 85 millimeters). In addition, manufacturing costs for active systems like these start at a few hundred euros.

Smart Fabs for the future development of vaccines and medication

The pandemic has resulted in an increased demand for vital medical products as well as for modern processes to manufacture progressive therapeutics and vaccines. We can also observe the development of a high demand for decentralized work models, and not just in the medical technology sector. To meet the tremendous time pressure, Smart Fabs had to be built in less than 12 months. “This required a number of factors to succeed, among them high throughput and reliability, full automation as well as volume and cost savings,” says Dr Gina Greco, Life Science, Diagnostics, Analytical Market Manager at Swiss sensor specialist Sensirion.

The experiences gathered during the pandemic have shown that life science, diagnostic and analytical instruments require further optimization. “Microfluidic systems combined with sensors are a key solution,” Greco emphasizes. Sensirion considers itself an expert for these components and has a broad portfolio that is well suited to meet today’s industrial challenges. These can be applied in every area of a pharmaceutical factory – be it in research and development, manufacturing or with regard to quality control and smart logistics.

COVID-19 and the extremely rapid development of effective vaccines have moved microfluidics and associated topics to the center of attention. Microsystems that can safely handle the smallest amounts of liquid and gas have become an integral part of medical technology. The 2021 COMPAMED Innovation Forum and the experts from the companies involved presented captivating examples and at the same time gave participants a preview of the topics and product innovations that will be showcased at COMPAMED 2021: from microtechnology and new materials to packaging solutions for the medical technology field and answers to any questions that may arise along the process chain for medical-technological product development and manufacturing.

For information about COMPAMED 2021: https://www.compamed-tradefair.com

Author: Klaus Jopp, freelance technical writer for science and technology (Hamburg, Germany)