Biosensors Are The Key to Ending the Pandemic

Think of all the things you’ve missed because of the pandemic. You’re not alone if you have 5 things off the top of your head. It’s hard to create your alternate reality where the pandemic doesn’t exist but it can motivate you to change things for the future.

We’re living in a pandemic. There have been 4.5 million deaths caused by COVID-19 related conditions. With the added effects from the Delta variant of COVID-19, this death toll is expected to increase exponentially within the next few months.

Luckily, we’re living in the era of developing ground-breaking technologies that will improve and save lives. The technologies that are developed today are going to change reality and bring us to the future. We won’t need to reminisce about the things we missed but look forward to everything we’ll gain. One that has possibly the most impact on our health, biosensors.

Biosensors are a branch of nanosensors (umbrella term for nanoscale devices that can detect and analyze any quantity) that are used to detect any biological or chemical reaction. They have massive applications in:

• Monitoring treatment or disease progression
• Environmental monitoring
• Food control
• Sanitation
• Drug discovery
• Forensics
• Biomedical research

There are currently hundreds of biosensors that are being built and researched every day with the goal of improving and learning about the world. For example, detecting water contaminants (like feces and other harmful chemicals) in third-world countries and detecting early-stage cancer.

Biosensors: the new wave in cancer diagnosis

How do biosensors help in our current situation?

Healthcare in most, if not all, countries is extremely human dependant. We need humans to operate hospital machinery, humans to analyze test results and humans to analyze patients. This causes lost time, human error and is extremely costly.

Let’s put this into perspective. If a new patient complaining of fever, headaches and shortness of breath they have to wait for someone to administer their COVID-19 test, perform the COIVD-19 test and interpret their test results. In some countries where healthcare isn’t efficient or effective, this three-step process alone can take up to a week for someone to receive their test results.

Biosensors allow for less human dependency, low cost, portability, real-time detection and high effectiveness. The efficiency of nanofabrication makes them cheap to manufacture and extremely sensitive and efficient.

Biosensors have the potential to help end the pandemic by accurately diagnosing new cases of COVID-19, checking for immunity to COVID-19, the possibilities are… pretty endless.

What type of biosensors could exist in hospitals?

The best part of biosensors is that they can detect and measure almost any biological or chemical reaction. There is no one-size-fits-all option, every biosensor is designed for each biological/chemical reaction. That is what gives biosensors their high sensitivity, specificity and efficiency. This is also why major healthcare systems are moving towards biosensors and away from older testing methods.

Note: Sensitivity is the ability to detect for the presence of a certain reaction, specificity is the ability to detect no presence of a certain reaction.

Take COVID-19 diagnosis, COVID diagnostic tests administered in Canada have lower sensitivity, if there is not enough virus in your body it declares a false negative result. A recent study from John Hopkins University found that false-negative results in patients with no symptoms ranged from 100% on Day 1 of infection to 67% on Day 4 of infection. Compared to the SD Biosensor STANDARD Q antigen test, where false negatives in patients with no symptoms were at 0.2%, date of infection unknown.

Biosensors are already playing an introductory role in helping to end the pandemic, but why stop there? There are three particularly interesting types of biosensors that are going to take the world of nanotech in health from an underdog to a key player.

Colorimetric, fluorescent and electrochemical biosensor methods are all based on biological/chemical reactions. Therefore, the main infrastructure of a biosensor is essentially built-in; biosensors don’t need to be reinvented for each reaction, simply tweaked.

Colorimetric Biosensors

Out of the three biosensor methods, colorimetric is possibly the most user-friendly, requires the least amount of maintenance and is ultimately the most popular. Colorimetric biosensors create changes of color that can be seen with the naked eye. So it requires little to no extra equipment besides the biosensor and whatever is being measured.

Basic colorimetric biosensors like pregnancy tests and the COVID-19 rapid antigen test mentioned before are regularly used and incredibly effective.

Here’s how it works:

A pregnancy test, the simplest colorimetric biosensor, works by detecting human chorionic gonadotrophin (hCG), a hormone that is only ever made if you’re pregnant.

1. Urine flows through the strip, everything except for hCG is filtered through the nitrocellulose membrane of the sample pad
2. hCG comes into the conjugation pad and binds with mobile antibodies that have dye-releasing enzymes attached
3. The hCG and antibody/enzyme combination travels to the test site where hCG will bind to an immobile antibody
4. The binding causes the enzyme to release the dye on the strip and lets you see the first line, usually indicating you’re pregnant
5. Excess mobile antibodies from the conjugation pad travel towards the control line and bind onto a third immobile antibody which proves the test is working

This procedure is pretty much how every colorimetric biosensor works, its simplicity and little need for human intervention makes it incredibly useful in building a biosensor that can be used by patients.

There is potential to use colorimetric biosensors to detect how much treatment a patient needs based on how much virus is in their body or even faster, precise COVID-19 test that can diagnose with 100% accuracy.

RNA-extraction-free nano-amplified colorimetric test for point-of-care clinical diagnosis of…

Fluorescent Biosensors

The problem with colorimetric biosensors is that they interact directly with the chemical or protein, something needs to attach to something in order to release the dye. Antibodies and dye-releasing enzymes need to react with the biomolecule to attach to each other. This can sometimes change the physical properties of fragile biomolecules like certain viral antigens if the binding activity is too aggressive.

Fluorescent biosensors use the fluorescent response of a mixture to detect and quantify a biological/chemical reaction. There is no binding activity in fluorescent sensors since it uses a light source as the ‘activator’ which doesn’t need to attach to any biomolecule, simply bounce off of them.

Here’s how it works

1. A microplate reader with fluorescence intensity (FI) detection uses a light source to excite a sample containing the chemical/biomolecule, which we’ll refer to as a molecule.
2. The excited molecule is transformed from neutral to charged
3. As the molecule returns to neutral, the energy is released as heat/light
4. This energy is detected by a photomultiplier tube (PMT)
5. The higher intensity of detectable energy shows more presence of the molecule

Even though fluorescent biosensors need particular equipment and have sometimes complicated processes, they aren’t time-consuming and are extremely sensitive. Compared to existing diagnosis tests like cell-based assays, there is no chance of altering fragile organic substances like viruses.

This means that we can use fluorescent biosensors for extremely fast and accurate COVID-19 diagnosing regardless of the infection date (during the early days of your infection there’s less virus in your body and may not be detected by traditional COVID-19 tests).

Electrochemical Biosensors

The coolest and most revolutionary biosensor, the electrochemical biosensor analyzes a biological sample by converting a biological event into an electric signal. Electrochemical combines elements of both colorimetric and fluorescent which makes it the most interesting and capable biosensor of the three.

An electrochemical biosensor has:

• Analyte — A substance of interest that needs detection
• Bioreceptor — A molecule that specifically recognizes the analyte. Upon interaction with the bioreceptor, a signal is generated and is termed bio-recognition.
• Transducer — In a biosensor, the role of the transducer is to convert the bio-recognition event into a measurable signal (signalization)
• Electronics — That part that processes the transducer signal and prepares it for display. The processed signals are then quantified by the display unit of the biosensor.
• Display — The output display of the biosensor

Each electrochemical biosensor can be customized to fit the sample which makes them accurate and selective. Like we’ve seen with COVID-19, early isolation and detection are key to fighting a virus.

Electrochemical biosensors give an easy, inexpensive way to detect the virus ASAP and later promote early isolation. This is a huge upgrade from conventional methods for detecting viruses where special equipment and personnel are needed.

Note: this is an example of an aptamer electrochemical biosensor, an aptamer is a short strand of DNA that binds specifically to the wanted biomolecule. In this example the aptamer is the analyte but you can also use enzymes, cells, antibodies, and other nanoparticles.

Here’s how it works

1. An aptamer that binds to the specific biomolecule, is attached to a graphene transducer
2. The biosensor is submerged in a sample containing the desired biomolecule
3. When the biomolecule binds onto the aptamer, oxidation and reduction reactions cause a movement of electrons is sent through the graphene transducer.
4. The electron signal is processed and categorized until it is ready to be displayed.
5. Results are displayed to the user

In this example, the biorecognition element is an aptamer, but there are other bioreceptors that you can use like enzymes, DNA, and antibodies. These unique bioreceptors are what give electrochemical biosensors their accuracy and selectivity, to the point where they can differentiate between cancerous cells and healthy cells.

There is huge potential to use electrochemical biosensors to help detect COVID-19 antibodies and diagnose COVID-19 even in the early stages of infection.

Paper-based electrochemical sensor can detect COVID-19 in less than five minutes

This is the time to embrace new technologies and find the limits of old methods so we can break them with the new. Biosensors are the key players in helping us to fight COVID-19 and ultimately end the pandemic. By making testing faster than ever before we can wipe the virus out, the solution we need is at our fingertips.

Takeaways

• Conventional testing methods for COVID-19 take time and aren’t 100% accurate, regardless of the date of infection
• Implementing biosensors can help stray away from a human-dependent healthcare system that costs time and money
• Colorimetric biosensor methods are user-friendly and can be used without the need for a professional
• Fluorometric biosensors use light to identify molecules and can be used with fragile molecules like viruses and antibodies
• Electrochemical biosensors are able to turn chemical/biological reactions into something we can notice
• Biosensors are what are going to help us create a better future while we fight the pandemic

Still Interested?

Here are some other goodies you can check out!

• https://pubs.acs.org/doi/10.1021/acsnano.0c04006
• https://www.sciencedaily.com/releases/2021/09/210907160547.htm