Size Matters

A Snapshot of the Big Revolution in Miniaturized Diagnostics

By Nancy B. Williams

Miniaturization has been a hot topic in diagnostics for some time now. But as more of these devices move from the experimental to the practical phase, it is becoming clear that miniaturization is about more than just size. Pushing the envelope to scale down these tools has led researchers down a path of reinventing how diagnostics work and what they are capable of.

The AACC Emerging Clinical and Laboratory Diagnostics conference, held April 24 and 25, in San Jose, California, showcased numerous miniaturization technologies that have great potential to improve patient care, from better drug dosing to wearable biosensors.

A Biosensor for Better Drug Dosing
An aptamer-based biosensor the size of a microscope slide has the potential to make drug dosing far more precise. The microfluidic electrochemical detector for in vivo continuous monitoring (MEDIC) tracks levels of specific drugs circulating in the blood in real time, explained H. Tom Soh, PhD, professor in materials, chemical, and mechanical engineering at the University of California, Santa Barbara.

The MEDIC can monitor drug concentrations in the blood continuously for hours, with the aim of personalized dosing that is more effective and less toxic. Doses can be tailored to individuals’ unique and changing biologic responses. Measuring pharmacokinetics, monitoring and administering drugs with narrow therapeutic windows, and managing medical conditions requiring continuous infusions could all be simplified with MEDIC, according to Soh.

The device relies on a microfluidic chamber lined with gold electrodes. Extending from each electrode are aptamers—synthesized DNA strands that recognize the analyte—with electrochemical reporters attached to them. When a target molecule comes in contact with an aptamer, the strand recognizes and folds around that molecule. Electrons from the tip of the strand are thus brought to the electrode at the aptamer’s base. The tiny jolt of current signals the molecule’s presence.
A liquid filter in the chip exploits differences in diffusivity so the system can work with whole blood. Modularity is another important part of the design. One can measure a wide range of biomolecules by swapping the aptamer probes. Future iterations of the device may make it possible to measure multiple molecules simultaneously in real-time.

Wearable Biosensors

An ion-selective epidermal biosensor for continuous skin pH monitoring. Photo courtesy Elecrozyme.
tattoo

The smiley-face e-tattoo is a wearable, printed electrochemical biosensor designed by Electrozyme. Adhering comfortably to the skin, such sensors can transduce metabolic information to allow real-time, quantitative analysis of chemical constituents of the wearer’s sweat.

The noninvasive platform has potential appeal for medical and mobile health applications—bedside monitoring and elder care, for example. The measurements can also aid in athletic and exercise training. The device can, for example, measure the pH level of the skin or indicators of dehydration and muscle fatigue—sodium, ammonium, and lactate—during exertion.

“The technology relies on two key innovations: the ability to extract biomarkers in the sweat in a noninvasive, continuous fashion, and the fact that we print all our biosensors using low-cost, widely deployed fabrication paradigms,” explained Electrozyme CEO Joshua Windmiller, PhD.

Employing ion-selective electrodes (ISE), commercially available temporary-transfer tattoo paper, and conventional thick-film fabrication techniques, the disposable sensor can be cost-effectively produced in large volume. Electrozyme’s screen-printed biosensors enable high-fidelity amperometric, voltammetric, and potentiometric electrochemical analyses of metabolites and electrolytes. The platform also has applications in environmental sensing and security monitoring.
These e-tattoos can also be customized into artistic or meaningful shapes. The smiley face design cleverly contains the electrodes: one eye is the analyte-sensitive ISE and the other eye is the reference electrode that completes the circuit.

Rapid and Scalable Biomarker Panels
A diagnostic platform employing silicon photonics lets users simultaneously analyze multiple proteins, DNA, or biomarkers from a single small sample. This multiplexing technology is appealing for clinical diagnostics in personalized medicine. The rapid, one-step process detects and quantifies relevant levels of target molecules in native body fluids and tissue biopsy samples.

“We’re taking advantage of very cost-effective, well-established, extremely robust fabrication for the silicon microelectronics industry and simply retasking it for diagnostics,” explained Ryan C. Bailey, PhD, an associate professor of chemistry at the University of Illinois at Urbana-Champaign. “We can ideally develop assays that can find very wide clinical adoption because it’s easy to make tens of thousands of sensors.”

A cassette of disposable silicon photonic sensors. Each chip can detect many unique biomarkers from a single sample. Photo courtesy Ryan Bailey, PhD.
silicon

Each silicon-on-insulator chip can have an array of up to 128 individually addressable photonic ring sensors. Each sensor traps and circulates light around a ring-resonator. A linear waveguide directs laser light past the ring-resonator and on to a photodetector. When the laser is tuned to the correct wavelength, the sensor removes all the light from the waveguide, producing a notch in the wavelength spectrum received at the photodetector. The wavelength of the notch shifts as organic molecules such as protein or nucleic acid bind to probe molecules on the ring.

Bailey likens the concept to a tuning fork, “but in our case, the resonance is optical.” The magnitude of the wavelength shift is directly proportional to the amount of material captured. That’s how target species are accurately quantified.

The versatile, scalable platform “can open the door toward translation of multiplexed assays into clinical care,” remarked Bailey. The company Genalyte is commercializing the technology.

Nancy B. Williams is a freelance writer in Arlington Heights, Ill. Email williams.nb@sbcglobal.net.

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