Discovering the unknown with Biosensors
Let’s just say that their a 2 different liquids, sprite and water. Now, if we add them into a container — keep in mind, that we don’t know the amount of drink there is.
Next, you simply just mix both the substances. Can you tell how much sprite or water is in the solution. I mean, it’s pretty hard since the solution looks transparent and there’s almost no difference in both drinks.
Now, let’s take that same concept and addd it to healthcare. Hundreds of years ago, doctors couldn’t even tell the difference between many things. That’s until we discovered the microscope. As years past, we developed much more advanced tech, and slowly started to realize that how small things actually are. Along with that, came a better understanding of things at a molecular level!
Finally in 1962, 2 chemists — Clark & Lyons, invented a device called “biosensors”. They discovered this by using amperometric enzyme electrode for the detection of oxygen. This helped uncover many of the human body’s ‘tiny’ secret.
Biosensors are basically small devices that are capable of measuring concentrations of analyte. A tritant is a solution with a known concentration and could be added to another solution — a solution that needs to have the concentration analyzed or determines. Meanwhile an analyte (or “trirand”) could be recognized as solutions without a certain concentration, therefore a substance in most cases the tritant is combined with the analyte. This technique is known as “titration” — uncovering the concentration of an unknown solution.
In 1700s, when chemistry was first used, chemists would just eyeball solutions and most of our discoveries were based off estimations. Fast forwards to 1956, came the first biosensor. It was created by an American Chemist — Leland C. Clark. Biosensors were originally used for oxygen detection in the blood (specifically meant to gauge oxygen in the blood), using an oxygen electrode. The oxygen electrode was coated with a gel composed of glucose oxidize enzyme → in order to compute blood sugar. As a result, the enzyme urease was used along with the electrode, and developed NH4++ ions. This was used to calculate urea in fluids (such as blood).
Currently, there are 3 different generations of Biosensors:
Type 1: The solution is distributed in the sensor and results in an electrical reactions
The electrons are relocated and combined with the molecular oxygen therefore. This decreases the oxygen concentration and the hydrogen peroxide (which is produced) is measured and analyzed.
Type 2: Mediators are installed into the sensor to produce a more precise outcome
This particular biosensors use toxic mediators or nano-materials to transport electrons to the electrode.
Type 3: Electrons are directly transferred from the enzyme to the electrode
Biosensors are able to detect and read through a molecular level of certain changes. The main features include: stability, cost, and sensitivity. All biosensors are used to measure the concentration of an analyte, and using detection methods, it processes this information, lastly displays it through the electronic system.
Data needs to processed by several materials in the biosensors
As information and data passes through it the biosensors, it interacts through 3 main parts:
- Electronic System
The bio-receptors are specifically designed to interact with a specific analyte, and expected to produce and effect that will be measured by the transducer. Biosensors can be classfiied into different types of bio-recpetor depending on which interaction it is aimed to: antigen, enzymes, DNA, cells. (these are all different types of bio-receptors)
An immunosensor (a certain type of biosensor) uses a binding affinity of antibodies for a specific antigen.
Antigen — a substance that helps produce antibodies for the immune system
Antibodies — a Y-shapes protein that binds to the body’s unfamiliar molecules, and signals the immune system to act
The way antigen and antibodies work, is similar to the lock and key fit — the antigen will combine with the antibody only with the right shape and structure. When combined, there is a physicochemical change that triggers florescent molecules, enzymes or radioisotopes and generates a signal. The only disadvantages of using antibodies as bio-receptors in sensors is that it is dependent on external conditions such as temperature. Having precise assay conditions can strongly impact the result of antibodies, and it is essential to be accurate.
Enzyme interactions are one of the most common and efficient bio-receptors. Enzymes are able to recognize analyze through multiple mechanisms such as the enzyme converts the analyte into a sensor-detectable. The main reasons why enzymes are most used is due to its ability to catalyze a large amount of reactions, recognize a group of analytes, and adapts to the several different transduction methods. Since enzymes are not combined in reactions, this allows the biosensors be reusable and used easily.
Biosensors that interact with nucleic acid based receptors can either be based into 2 categories:
- Genosensors: complementary base pairing interactions
- Aptasensors: nucleic acid based antibody mimics (aptamers)
DNA is made up of base pairing — adenine:thymine (A+T) and cytosine:guanine (C+G). If the biosensors are targeted towards a certain sequence, then complementary sequences can be synthesized, labelled, and then immobilized on the sensor.
The hybridization event can be recognized when DNA/RNA is being asserted. In the latter, the aptamers are generated to react with non-covalent interactions. The aptamers are specifically created to target cells and viruses.
Hybridization: combining atomic orbitals into new hybrid orbitals
Orbitals: places that surround the nucleus of an atom (where the electrons are expected to be)
Cells are also used as bio-receptors due to its sensitivity, adaptability, and response to its environment. Cells easily attach themsleves to the surface of the biosensors therefore, they can be immobilized efficiently. Since they are able to remain active for a longer time period, and they have a high reproducibility rate — this allows them to be reusable.
The bio-transducer is an element that converts one form of energy to another. The main role of the transducer in a biosensor is to recognize a reaction and transform the event in a measurable signal. This process of conversion is known as signalisation. Majority of transducers are able to produce either optical or electrical signals that are equivalent to the amount of analyte-bioreceptor interactions.
Normally, the enzyme is deactivated by a specific method — this way it is in near contact with the transducer. The analyte connects with the biological, and results in an electronic reaction that could be calculated.
Last stop, the electronic system! The electronic system is the last component of biosensors. This section helps processes the transduced signal and prepares it for display. There are 3 main parts of the electronic system (the components are in order of which the signal passes through):
- Signal amplifier — Converts any biological materials into an electrical signal
- Processor — Analyzes information that has been received by the signal amplifiers. Interprets the information that has been converted.
- Display — The display is composed of a user interpretation system. This part consists of both hardware and software that shows the results of what the biosensor has processed. Normally, the output is shown through numbers or images.
Based on the the different types of transducer or products used for the biosensor — it is classified into a different categories. The main types of biosensors include:
- Electrochemical Biosensors
On a very basic term: electrochemical biosensors are biosensors that work using an electrochemical transducer. The main role of this biosensor is to detect biological materials such as enzymes. Electrochemical biosensors are based on the reaction of enzymatic catalysis (EM). EM is the increase in the rate of a process by a biological molecule. The molecule acted upon an enzyme — substrate, includes 3 electrodes: counter, reference and working type.
Electrochemical biosensors are classified into four types
- Amperometric Biosensors — a device that measures the current resulting the oxidation or reduction of an electroactive biological element
- Potentiometric Biosensors — this sensor has biological element incorporating that is connected to a physico-chemical transducer, providing an electrical potential (analytical signal)
- Impedimetric Biosensors — immobilizing biological recognition elements onto an electrode surface (Immobilization: an enzyme attached to an inert, insoluble material)
- Voltammetric Biosensors — information is obtained by varying potential, then analyzing the resulting current. This is an amperometric technique.
2. Immunosensors Biosensor
Immunosensor biosensors are devices that immunochemical reactions are coupled to a transducer. They can be divided into two categories: non-labeled, and labeled immunosensors. Non-labeled immunosensors are designed so that the immunocomplex (for example, antigens/antibodies) is measured by the physical changes made by the formation. In the other hand, a labeled immunosensor consists of a sensitively detectable label. Therefore the immunocomplex is determined through measurement of the label.
These are just 2 examples of biosensors, however there are many more: magnetic, optical, piezoelectric, and more. These types of biosensors could be applied for healthcare, agriculture, and more. Biosensors have the potential of measuring accurate concentrations of substances that aren’t determined.
The average cost of biosensors are between $1000-$5000. Due to its cost, most hospitals and organizations prefer purchasing reusable and efficient biosensors. However, the cost for the development of biosensors can range between $20–$30 million dollars! On top of that, the amount of time it takes for the development is around 7–10 years. The amount of financial investments needed for a very ‘small’ device questions if this product is even efficient — currently, new strategies are trying to be established: a solution that both cost-efficient and effective. But until then, we’re stuck with biosensors!
Hey, I’m Sanvi! I’m a bio-tech enthusiast, and I’m currently doing research on Cystic Fibrosis. If you enjoyed this article, be sure to give it a clap 👏. Thanks!