Advances in Nanomaterials for Detecting Disease Biomarkers

The early diagnosis of disease is one of the most important factors in a patient’s clinical treatment. Depending on the type of disease, an early diagnosis may broaden the range of potential treatment options available, increase the opportunities for informed decision-making  and may even allow for the deployment of preventative measures that can significantly improve a patient’s quality of life and odds of making a full recovery.

The non-invasive detection of disease-related biomarkers plays a key role in improving the early diagnosis of disease. In recent years, biosensors capable of detecting biomarkers in bodily fluids have stood out as a key technology in this field, largely thanks to their cost-effectiveness, portability and rapid response times.

Advanced biosensors use nanomaterials to improve their sensitivity and boost signal amplification. Functionalized nanomaterials can also be used to further enhance sensor properties such as resolution, response time, linearity, repeatability, robustness, biocompatibility and stability.

This article explores the discovery and continued development of the nanotechnologies that are underpinning advancements in biomarker sensing today.

How do biosensors work?

Biomarkers – a portmanteau of the phrase “biological marker” – are measurable indicators that can be used to assess some kind of biological state or condition. Examples of biomarkers include everything from a person’s blood pressure and heart rate to genetic markers and other molecules that can be observed using modern laboratory science.

Two of the most widely used laboratory methods for biomarker detection and quantification are enzyme-linked immunosorbent assay and polymerase chain reaction methods. While these techniques do have many advantages – including high sensitivity, selectivity and repeatability – they are somewhat limited by their long response times and their consumption of reagents required for every analytical run. This makes them a less practical option for continued monitoring or for rapid biomarker detection for point-of-care applications.

Biosensors are a leading alternative for biomarker detection. A biosensor is made up of two main components: the biosensing component that binds to the target biomarker, and a transducer that converts this binding event into a measurable signal for detection. There are a wide variety of different transducer systems used in biomarkers, including electrochemical, optical, gravimetric, colorimetric and field-effect transistor-based sensors.

Advanced nanomaterials push the detection limits of biosensors

In recent years, the use of nanomaterials has become a major focus of biosensor development.

Because of their unique structures and small size, nanomaterials often display unique electrical, optical, magnetic and thermal properties that can help to enhance a particular biological signal and improve the sensitivity of a biosensor.

For example, functionalized nanomaterials are frequently used as a substrate modifier in biosensors, as their high surface-to-volume ratio makes them an ideal surface for immobilizing analytes of interest. This effectively increases the density of the biomarker molecule, improving the overall sensitivity of the biomarker.

There are many other mechanisms which nanomaterials can help enhance the function of biosensors and many different nanomaterial classes have been effectively utilized in biosensing.

Metallic nanoparticles

Noble metal (i.e., gold, silver, platinum) nanoparticles are used extensively in many industrial and scientific applications, such as catalytic converters, due to their good stability and ease of modification.

Gold nanoparticles (AuNPs) are of particular interest for optical and electrochemical biosensors. This is largely due to their high conductivity, biocompatibility, stability and the ease with which their surface can be modified by thiol groups.

In electrochemical biosensing, AuNPs can be advantageous when the target biomarker molecules are present in small amounts, and thus the electrochemical signals are relatively weak. The very high electrical conductivity of AuNPs allows for the electrochemical signals from such redox reactions to still be detected with high sensitivity and selectivity.

Noble metal nanoparticles are also favored in optical biosensors as their colors can be detected with the naked eye. Their color may also change depending on their state, which again is of use in biosensing. For example, researchers have used surface-functionalized AuNPs in biosensing platforms to detect the SARS-CoV-2 coronavirus, relying on the red-to-purple color change that occurs when AuNPs begin to aggregate together around a virus particle.

Noble metal nanoparticles have also been used for viral pathogen detection in electrochemical biosensors, including for viruses such as SARS-CoV-2, human immunodeficiency virus, hepatitis, influenza and Zika virus.

Carbon-based nanomaterials

Carbon nanomaterials are another popular type of nanomaterial that is commonly incorporated into optical and electrochemical biosensing platforms.

The unique structure of carbon nanotubes (CNTs) makes them of great interest for biomarker sensing applications. The tubular structure results in a very high surface area-to-volume and aspect ratio, while retaining good chemical stability and electrical conductivity. In electrochemical biosensors, CNTs can be used to increase the active surface areas of the electrodes and improve electron transfer, which can increase the sensitivity and lower the limit of detection for electrochemical sensors.

Modified CNTs have been demonstrated in electrochemical biosensors that can quantify multiplex biomarkers in human blood serum for cancer diagnosis.

Depending on their physical structure, CNTs may also have fluorescent properties that can be leveraged for fluorescence-based optical biosensors.

Graphene – a two-dimensional sheet of carbon atoms arranged in a lattice – is a useful material for wearable biosensors, where graphene’s biocompatibility and flexibility make it uniquely suitable for enhancing performance in wearable device electrodes. Graphene-enhanced electrochemical sensor electrodes are a potential solution for the challenges of real-time health monitoring and personalized medicine, with this technology already having been demonstrated in the real-time non-invasive tracking of biomarkers relating to inflammation, diabetes, gout and heart diseases.

Quantum dots

Quantum dots (QDs), sometimes known as “zero-dimensional” materials, are traditionally semiconductor particles (though can also be made of graphene or regular carbon) measuring less than 10 nanometers in size, and made up of just a few thousand atoms in total. At this small size, QDs are strongly affected by quantum phenomena that play a significant role in how the dots absorb and emit light. The fact that their behavior can only be explained by quantum physics – not the laws of classical physics – has led to QDs being explored for a vast range of different applications, including in medicine, batteries, catalysis and as a component of biomarker-detecting biosensors.

Their strange light absorption properties make QDs a prime target for use in optical fluorescence biomarker detection. QDs can be conjugated with antibodies, aptamers or other molecules that will target a specific biomarker and act as light-emitting probes for in vitro assays. Compared to traditional options for fluorescent dyes, QDs are advantageous as they do not suffer from the same issues of photo-bleaching and they can be easily tuned to emit different wavelengths of light.

While research into QDs is still in its relative infancy, biosensing devices that use QDs have been developed for detecting biomarkers relating to cardiovascular disease, tuberculosis and breast cancer.

Challenges and opportunities in nanotechnology

Nanomaterials have a very particular appeal for enabling better biomarker analysis. There is a diverse range of different materials that offer unique size- and shape-dependent properties that could be used to enhance analytical biosensors. The potential for nanomaterials to enable rapid, cost-effective, portable biomarker test kits is an attractive prospect for those looking to improve point-of-care diagnostics and continued health monitoring in individuals suffering from serious diseases or cancers.

While the future outlook for these systems is bright, there are still several challenges that these nanomaterial-enabled biosensors must overcome. Firstly, while there are some examples of commercially available biosensors that feature nanotechnology, the majority of this type of biomarker biosensor development is in the laboratory research phase and must still be proven to be commercially viable.

One aspect of this challenge is that synthesizing and characterizing these nanomaterials often requires the efforts of very skilled technicians. Ensuring the reproducibility and stability of nanoparticle-based sensors as they are produced and used in real-world situations is also key; for real ease-of-use, a sensor must be stable enough to analyze whole blood without any additional sample dilution or processing, for example. With portability being a desired feature, it is also important that these technologies can demonstrate a good shelf-life within reasonable expected temperature conditions.

Despite these challenges, innovation continues to drive increasingly novel nanomaterials and new ways of detecting and quantifying disease-related biomarkers. With the advancement of these technologies, scientists hope to further improve point-of-care and personalized diagnostics to deliver the best possible outcomes for patients.