Implantable optical biosensors: The “bright” future of diagnostic medicine?

Implantable optical biosensors: The “bright” future of diagnostic medicine?

By Deeksha Chopra

There is burgeoning demand for point-of-care testing and real-time biomarker monitoring tools in the field of biomedicine to tackle chronic health issues such as, but not limited to, cardiac and neurodegenerative disorders as well as diabetes. Recent advances in the development of state-of-the-art biosensors offer tremendous potential in the field of clinical diagnostic medicine. In fact, the biosensor market is projected to exceed $28 billion by the year 2024. In this article, we shine light on optical biosensors and discuss how these sensors are being reformed for implantable use.

Just what are these biosensors?

Biosensors are devices that can successfully identify the presence and levels of a spectrum of biological analytes, from biological structures to microorganisms. As the name suggests, biosensors couple the power of biological sensing elements such as proteins, nucleic acids, or complex biomaterials with a transducer component that transmits the produced signals to enable the quantification of biomolecules. Based on the transducing mechanisms, biosensors can be classified as electrochemical, thermal, or optical. Of these, optical biosensors are the most common and offer direct, label-free or label-based real-time detection of biomolecules. Optical detection systems harness the power of an optical field and a biorecognition element. Importantly, optical biosensors have an edge over other analytical technologies as they are more specific, more sensitive, more cost-effective, and smaller in size.

Schematic of optical sensor detection. Image source: IntechOpen

What’s new in the field of optical biosensors?

Colossal efforts are being made by life scientists towards optimizing and improving optical biosensors for implantable use. Many recent studies describe how optical biosensing technology can be used to drive new innovations in the field of biomedical diagnostics and therapeutics. This section will highlight some of the most recent findings in this area.

Nanotube biosensors for bioanalytes:

Optical biosensors made using single-walled nanotubes are one of the most promising technologies in the field. These nanotubes are great candidates for implantation as they have the ability to transmit signals from beneath the skin without the need for electrical connectors that would require skin penetration. Unfortunately, fluctuating salt concentration in the biofluids is known to affect the sensitivity and specificity of single-stranded DNA-covered nanotube optical biosensors, representing a major challenge for this technology.

To overcome this hurdle, a team of scientists at the École Polytechnique Fédérale de Lausanne have recently devised stable optical biosensors to detect analytes in biological fluids. According to Ardemis Boghossian, the principal investigator of the lab optimizing this tool, “What we did was wrap nanotubes with ‘xeno’ nucleic acid (XNA), or synthetic DNA that can tolerate the variation in salt concentrations that our bodies naturally undergo, to deliver a more stable signal.” To this end, he added, “We think these results are encouraging for developing the next generation of optical biosensors that are more promising for implantable sensing applications such as continuous monitoring.”

Miniaturized optoelectronics for optogenetics:

We can all appreciate that the proper functioning of our nervous system depends heavily on intricately weaved neuronal circuitry, much of which is still waiting to be deciphered. Optogenetics, is a fascinating technique whereby light signals are capable of turning on and off living cells, typically neuronal cells that have been modified to express light-sensitive ion channels. This system allows for the visualization of nerve cell distribution patterns and can trigger and control specific neuronal cell types. This methodology could be instrumental in investigating and treating various neurodegenerative disorders.

Traditionally, optogenetics has been studied by surgically inserting optical fibers into an animal’s brain, and they are secured to the head with a plastic cap. The opposite end of the fibers are connected to a laser source to funnel light into the neuronal cells. One big disadvantage of this method is that these cables add bulk on the animal’s head and often restrict their movement. Moreover, the glass fibers inserted into the brain tissue can cause discomfort and tissue damage, altering their behavior. To overcome these challenges, John A. Rogers and his colleagues at Northwestern University successfully developed a sophisticated cable-free implantable optical system that is rolled into a single unit consisting of an LED light source and precision optical sensors. The team commercialized this system in 2016 under the name of NeuroLux. These implants are not only wireless, but are also thin and flexible. “Optogenetic modifications in mice have no adverse impacts to their health,” said Rogers, one of the cofounders of NeuroLux, “so it’s conceivable that these approaches could one day be approved for safe use in humans.”

Fluorescence-based glucose sensors:

Despite the market availability of continuous glucose monitoring devices, many patients with diabetes that use insulin still fight to maintain steady levels of glucose during abrupt episodes of hypoglycemia. Launched by Senseionics, Eversense is the world’s first long-term implantable continuous glucose monitoring system released in the United States after getting an approval from FDA.

The system is a combination of a fluorescent glucose-responsive sensor, LED light sources, photodiodes to detect fluorescent signals, and a wearable transmitter that communicates the glucose concentrations to a mobile app. The implantable sensor system is inserted under the skin of the upper arm with a minor surgery. Multicenter clinical trials clearly demonstrate the effectiveness and safety of this glucose monitoring system over a 90-day period. It is only a matter of time until these fully implantable fluorescence sensors will be optimized for long-term analysis of a wide array of clinically relevant biomolecules with very high precision.

The future?

Looking at the current trends and developments in the field of implantable optical biosensors, it is safe to assume that this technology can have a wide range of applications in preclinical drug toxicity studies, clinical biomarker monitoring, and therapeutic drug delivery. We look forward to the exciting milestones in the world of implantable optical biosensing!

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