One test to diagnose them all — that is the promise of biosensors based on aptamers, in the growing field of diagnosing human health problems.
Aptamers are like molecular fishing hooks. They are short, single-stranded DNA or RNA molecules and have a useful ability to selectively latch on to specific target molecules in bodily fluids like urine, blood, and saliva depending on their programming.
By programming aptamers to recognise and latch on to disease biomarkers or therapeutic targets, researchers can visualise these interactions using spectroscopy and other advanced techniques, developing faster and more accurate tests as a result.
The kicker? Such tests could cost as little as Rs 500, and could be used to spot everything from cancers to Ebola to COVID-19.
Aptamer-based biosensors could someday bring diagnoses of a range of conditions straight to our homes. Here is how they work.
The discovery
In the early 1990s, researchers studying sequences of molecules found that certain sequences could selectively bind to specific target molecules, the same way that antibodies bind to antigens.
This discovery opened a new world of possibilities for biosensors, as it suggested that aptamers, essentially sequences of single-stranded DNA or RNA, could be used to detect target molecules.
Due to their unique three-dimensional structures, flexibility, and folding capabilities, aptamers can bind tightly to specific target molecules, including proteins, peptides, small molecules and even whole cells, with high sensitivity and specificity.
In 1995, Larry Gold and his team developed the first aptamer-based biosensor to detect an antibiotic called kanamycin.
Aptamer-based biosensors have since been developed to detect a range of molecules and have advantages such as high sensitivity and specificity, low cost and ease of production. The aptamers are cheaper to manufacture than antibodies, making them an attractive sensor option. Today, generating an aptamer could cost less than Rs 500, says Dr Arghya Sett, post-doctoral research scientist at the Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, speaking with Happiest Health.
Aptamers also have potential applications in medicine, environmental monitoring, and food safety.
Apt for aptamers
Swiss biotechnology company Achiko has developed a non-invasive, rapid COVID-19 test kit that uses aptamer-based biosensors and digital technology to identify the SARS-CoV-2 spike protein in saliva samples. The result, a simple, quick and affordable way to detect the virus in resource-limited areas, received approval from Indonesia’s health ministry.
“Through the remarkable ability of aptamers to precisely target specific molecules, we can create ultra-sensitive biosensors that can revolutionise disease diagnosis and small molecule detection,” Dr Sett says.
Detecting the aptamer
Spectroscopy techniques, which act like a fishing camera, enable scientists to see the aptamer “hooking on to” its target molecule. Spectroscopy can provide real-time detection without labels or tags, simplifying the detection process, reducing the cost, and offering advantages over traditional methods. Using this technique, scientists can create highly sensitive biosensors with various applications.
Other detection methods are electrochemical methods, surface plasmon resonance (SPR), mass spectrometry, and other label-free or label-based detection approaches.
One of the most significant advantages of aptamer-based biosensors is that they can customised. Aptamers are customisable and aptamer-based biosensors can detect biomarkers across various molecular levels. This can provide a comprehensive view of a person’s health, enabling detection of emerging health problems early and personalised treatment plans.
A better biosensor
Traditional biosensors have excelled in tracking specific molecules like glucose, cholesterol or certain proteins. But their limitations become apparent when tackling more than one at a time.
Aptamers, however, offer a transformative solution. Their ability is akin to fitting a key into a lock. Integrating aptamers into biosensors can unleash their multiplexing power, enabling the detection of a multitude of substances all at once.
This breakthrough is significant. Think of biosensors that can do more than just detect one thing at a time. They can give a full picture of many molecules in our blood. They can find antibiotics in water or spot different types of bacteria. Biosensors using aptamers show they can be used in many ways and have a lot of potential.
Large scale studies possible
This expands on previous microneedle sensors that could only detect specific molecules. The new sensors can be used multiple times and tested successfully in the lab and live animal settings.
The best example is the SOMAscan assay which can do proteome analysis (large-scale study of proteins) to detect more than 7,000 protein biomarkers with very high (‘femtomolar’) sensitivity.
`Femtomolar’ refers to a concentration of a substance and is equivalent to one quadrillionth (10 to the power of minus 15) of a mole per litre of solution. It is like finding a single drop of water in 20 Olympics-standard swimming pools.
US-based proteomics company SomaLogic has also been testing new ways to predict and understand cancer. Using its SOMAscan to look at 30,000 samples from the EPIC study, it measured 210 million proteins. Other companies, like AptameX, are also working on similar areas.
Dr. Agnivo Gosai, a research scientist at Corning Incorporated in New York, believes this will aid in predicting cancer. He says, “This will help researchers in predicting cancer by better understanding its nature.” Dr. Gosai is the author of a paper published in the International Journal of Molecular Sciences
Insulin tracking and other uses
Aptamer-based biosensors can also monitor insulin release in real-time, aiding researchers in studying insulin release mechanisms and developing better treatments for diabetes. Compared to traditional methods, aptamer-based insulin monitoring can be more sensitive, specific, stable, easy to produce and reusable.
Aptamers could play a key role in Ebola detection. For this, researchers have crafted a unique device: an electrochemical aptasensor. Both portable and cost-effective, it is designed to identify specific Ebola-related proteins. Remarkably, it completes this task in under an hour. Ease-of-use is another feature of the aptasensor as it operates without electricity or cooling. This makes it a perfect fit for remote areas, where Ebola outbreaks are common.
According to Dr Gosai, traditional methods for detecting the Ebola virus require a specialised laboratory and trained technicians. The researchers have developed a unique aptamer sensor capable of identifying the virus from just a single drop of blood. They noted that once the blood cells are filtered out, one can obtain results within an hour.
Hope on the horizon
Before these biosensors can reach hospitals, they must pass tests set by the US Food and Drug Administration.
Due to their low immunogenicity, aptamers pose low risk of causing adverse immune responses . “It is expected that aptamer-based sensors will be available for human use in another 10 years,” adds Dr Gosai.
Aptamers also hold immense promise in detecting biomarkers for acute kidney injury. Recent studies have reported positive preliminary results, although further experiments are necessary to confirm these findings.
“Although only a limited number of targets are commercially detected using aptamers, the future is not far away when we will witness a repertoire of aptamers available to detect many significant targets for the safety and protection of humankind and the environment,” adds Dr Sett.
