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Digital Microfluidic Platform Being Developed for On-the-Fly Swapping of Biosensors for Diagnostic Use

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NEW YORK (360Dx) – Researchers at the University of Toronto are developing a digital microfluidic (DMF) platform that enables plug-and-play capabilities — the ability to swap various sensing technologies that measure different analytes for a range of medical diagnostic applications.

In a study recently published in Analytical Chemistry, they described the development of a proof-of-concept digital microfluidic platform that operated effectively with a variety of sensor methods, including commercial biosensors for measuring glucose and β-ketone and a custom paper-based electrochemical sensor for measuring lactate.

The study demonstrates for the first time the plug-and-play capabilities of "diverse commercial and custom biosensors for measurements in serial or in parallel on a DMF device," Shih-Kang Scott Fan, a microfluidics researcher at National Taiwan University not affiliated with the study, said in an interview.

"[This] extends the sensing potential of DMF and facilitates sample handling for biosensors," said Fan. "The work allows possible commercialization of [plug-and-play] DMF with optimized wicks bridging droplets and hot swapping of biosensors."

In general, a digital microfluidics platform uses an array of insulated electrodes to manipulate discrete droplets, including droplets of whole blood, that are often sandwiched between hydrophobic top and bottom plates. Droplets can be dispensed, split, mixed, and merged to perform a variety of automated routines and assays.

"By individually and concurrently driving multiple droplets, complicated protocols of sample preparation can be easily done by DMF," Fan said. "To complete bioassays, compact and exchangeable biosensors are essential, especially to point-of-care applications."

Ryan and Christian Fobel, former researchers in the Wheeler laboratory and developers of electronic systems that control the plug-and-play microfluidics platform, have founded Sci-Bots to sell a DMF system they have developed. Most of the electronics and software used in the system is open source.

"Digital microfluidics is one of the most versatile techniques for automated liquid handling out there," Ryan Fobel said. "What makes it unique is that relatively generic chips can be reconfigured through software."

The advantage of this type of platform is that it is inherently flexible, said Richard Piffer Soares de Campos, a postdoctoral fellow at Wheeler's Microfluidics Lab in the University of Toronto, and one of the developers of the DMF platform described in Analytical Chemistry, in an interview.

He noted that with colleagues in the Wheeler lab, he has experimented with installing electrochemical detectors on the DMF platform, but there are drawbacks to permanently modifying the platform. "After modifying the platform, you can only use that device to detect the specific analyte for which you have made the system's electrode sensitive," he said.

As a result, a more advanced platform that he and his colleagues are developing enables connecting different sensing technologies and could allow detection and measurement of different analytes during one test run and using one patient sample, he said.

To enable this capability, their proof-of-concept platform has a slot in its structure that enables quickly unplugging an existing sensor and plugging in a new one.

They demonstrated that it was possible to swap sensors on the fly and enable convenient implementation of complex processes such as automated analysis of blood samples. Further, they showed the suitability of using the plug-and-play platform and its sensors in tandem with other sensing modalities, combining biosensor-based electrochemical measurement of glucose with a chemiluminescent magnetic bead-based sandwich immunoassay for insulin.

Detection using digital microfluidic devices can be slightly less sensitive and specific than laboratory-based ELISA testing in matched serum samples, but some researchers believe that they are still suitable for serosurveillance applications and are particularly useful in areas where centralized laboratories are unavailable.

UK-based University of Hertfordshire and the Defense Science and Technology Laboratory (DSTL) recently reported that they have developed a proof-of-concept digital microfluidic platform that detects four classes of simulated chemical and biological warfare agents on a chip — toxins, vegetative bacteria, bacterial spores, and viruses.

The Wheeler laboratory has already participated in testing of an earlier digital microfluidic platform in remote settings for clinical diagnostics. The group published the results of a study last year in which they used an optimized inkjet-printed microfluidic cartridge and a portable control system to perform serological immunoassays.

The microfluidic platform required light for chemiluminescent detection. With the new plug-and-play approach, they are investigating slotting electrochemical sensors into the device, which makes it more robust and further reduces its footprint, a benefit for non-lab applications, Piffer Soares de Campos said.

To demonstrate the platform's capabilities in the current study, they swapped commercial sensors that separately measured blood glucose and β-ketone, which are used to monitor patients with diabetes. The also showed that the proof-of-concept platform operates effectively with custom-made sensors by connecting it with the paper-based electrochemical sensor.

The DMF platform has a broad range of potential clinical diagnostic applications, Piffer Soares de Campos said, including measuring many analytes that are currently detected by clinical chemistry laboratories.

He noted that research led by Christopher Dixon, a researcher in the Wheeler lab, is focused on reducing the cost of manufacturing DMF platforms using inkjet printing and a roll-coating process that is scalable and therefore suitable for mass production.

They see it as a higher-performance alternative to lateral flow, point-of-care assays used outside of laboratories to detect infectious diseases.

The researchers reported that the performance of the inkjet-printed devices is on par with that of more expensive DMF devices fabricated in a cleanroom. With the new manufacturing approach, they spend less than $1 to manufacture each microfluidic platform compared with $40 per platform manufactured in a cleanroom.

The researchers plan on further field trials to validate their DMF platforms, and are considering various options for commercialization, including potentially forming startup companies and licensing technology to existing companies that could assist with pursuing regulatory clearances, Piffer Soares de Campos said.