INTRODUCTION:

Due to the increasing need for quick, precise, and affordable diagnostic instruments in the fields of biotechnology, environmental monitoring, food safety, and healthcare, biosensor technology has advanced significantly in recent years. A biosensor is an analytical tool that combines a transducer to transform a biological response into an electrical, optical, or mechanical signal with a biological recognition element (e.g., enzymes, antibodies, nucleic acids, or cells). Real-time health monitoring, tailored treatment, and early disease identification are all made possible by developments in biosensor technology, which is revolutionising healthcare. The use of biosensors for illness monitoring, diagnosis, and treatment is crucial in clinical analysis when evaluating them in the healthcare industry. Another important milestone in this area is the creation of equipment that patients can use on their own. Biosensors are used in environmental, food, and water safety analysis in addition to biomedical applications. The need for quick, accurate, and affordable testing tools in the fields of biological sciences, environmental monitoring, food hygiene, and healthcare has led to significant advancements in biological sensor technology during the last ten years. In order to transform a biological reaction into an electrical, optical, or structural signal, by facilitating real-time health monitoring, personalised treatment, andearlydisease identification, biosensor innovation break through are revolutionising healthcare. The broadest definition of a biosensor is an analytical tool that includes a bioreceptor (biological recognition element; enzyme, DNA, antibody, cell.¹

Upcoming Advancements:

1. Point of-Care Diagnostics: Convenient, portable biosensors for medical use.

2. Wearable Biosensors: Combining wearable technology with fitness trackers and smartwatches.

3. Implantable Biosensors: The creation of biosensors that can be implanted for ongoing surveillance.

4. Nano biosensors: Increasing sensitivity and specificity through the use of nanotechnology.

5. Artificial Intelligence and Machine Learning: Using AI and ML algorithms to enhance decision-making and accuracy.^2,4

American biochemist "L.L. Clark" created the first biosensor in 1950. The Clark electrode, also known as the oxygen electrode, is the electrode used in this biosensor, which measures the amount of oxygen in the blood. To calculate blood sugar, a gel containing the glucose oxidising enzyme was then placed on top of the oxygen electrode. Accordingly, an electrode specifically designed for NH4++ions was used in conjunction with the urease enzyme to measure the amount of urea in bodily fluids like blood and urine.³

Main Components of Biosensor:

The biosensor's block diagram is made up of three sections: the sensor, the transducer, and associated electrons. The sensor, a biological component in the first segment, is followed by the detector, which alters the signal created by the analyses contact and displays the data in an understandable format. The final section includes the CPU, display unit, and amplifier—also known as a signal conditioning circuit⁵

1.Nanotechnology Integration: Nano-materials such as graphene, carbon nanotubes, gold nanoparticles, and quantum dots improve biosensor sensitivity, selectivity, and miniaturisation. Nano-materials improve electron transfer rates, increase the surface area accessible for biomolecule interaction, and enable low-concentration analyse detection.⁵

Fig.1. Schematic diagram of main components of biosensors.

2. Biosensors that are implantable and wearable:

Wearable biological sensors incorporated into clocks, patches, and clothes can continuously measure real-time physiological features such as heart rate, blood sugar levels, and sweat components. Implantable biosensors, such as glucose monitors used in diabetes therapy, enable constant monitoring within with minimal irritation.^5,6

3. Portable and Point-of-Care Biosensors:

Portable biosensors, such as smartphone-based systems and lateral flow assays, provide quick on-site diagnosis of illnesses like influenza, COVID-19, and HIV. These tools are useful in environments with limited resources since they yield findings quickly and require little sample preparation.^5,6

4. Biosensors Based on CRISPR:

Highly specific gene and pathogen identification has been made possible by the combination of biosensors and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology. Viral RNA and single nucleotide polymorphisms (SNPs) can be accurately detected using CRISPR-based biosensors.^5,6

5. Machine learning and artificial intelligence (AI):

Biosensors are using AI and machine learning algorithms to enhance data processing, pattern identification, and decision-making. This improves biosensors' precision and forecasting power, especially when working with intricate biological materials.^5,6

6. Lab-on-a-Chip and Multi-Analyse Detection Systems:

Modern biosensors, which use lab-on-a-chip platforms and micro fluidics, may detect various biomarkers at simultaneously. These devices allow for detailed analysis in a condensed manner while reducing sample volume and enhancing performance.^5,6

Types of Biosensors:

Fig.2. Flow chart of biosensors.

>Bioreceptor Based:

1. Enzyme-based Biosensors:

Biosensors are devices that detect biological components or changes in biological systems and convert the signals into measurable data. A signal processor, a transducer, and a bio receptor are typically its three main components. The transduction mechanism or bio receptor type determines the classification of different biosensors.⁹

The main kinds are as follows:

These use enzymes as the bioreceptor. The enzyme interacts with the target substance, resulting in a measurable signal. For example, glucose biosensors use the enzyme glucose oxidase to detect glucose levels.⁹

Fig.3. Enzyme- based biosensor.

2. Immunosensors, or Antibody-Based Biosensors:

These use antibodies as a bio receptor. These biosensors are highly selective since antibodies only bind to antigens, or foreign substances. Immune- sensors are often used to detect infections and other biomolecules such as hormones.²

Fig.4.Antibody based biosensors.

Application:

1. Diagnostics: Development of a Portable Biosensor Immunoassay Analyser for Infectious Diseases"

2. "Biosensor Immunoassay Analysers for Cancer Biomarker Detection: A Review"

3. "Food Safety Testing: Applications of Biosensor Immunoassay Analysers for Rapid Detection of Pathogens"^7,8

4. DNA Biosensors (Gene sensors):

These utilise nucleic acids (DNA or RNA) as the bio receptor. They are extensively employed in environmental monitoring, forensics, and diagnostics to find particular DNA sequences, mutations, or genetic material.¹⁴

Fig.5. Diagram of DNA biosensors.

2.Transducer-based:

Biosensors employ a variety of transducers to transform the biological interaction between the bio receptor and the target analyse into a quantifiable signal. The transducer converts the biological response into a quantifiable output, such as an electrical, optical, or thermal signal. The following are the main types of transducer-based biosensors:^10,11

1. Electrochemical Biosensors:

How they work: These biosensors use electrochemical transducers to measure changes in electrical properties (e.g., potential, current, or impedance) caused by the interaction between the bio receptor and the analyse.¹¹

Types of electrochemical measurements:

1. Potentiometric: Measures changes in the electrical potential (voltage) between two electrodes.

2. Ampere metric: Measures changes in current as a result of redox reactions that occur when the analyse binds to the bio receptor.

3. Impediment: Measures changes in the impedance (resistance to current flow) in response the Interaction.¹²

Applications:

Electrochemical biosensors are commonly used in glucose monitoring, lactate detection, environmental analysis (e.g., heavy metal detection), and medical diagnostics^7,8

2. Optical Biosensors:

How they work: Optical transducers measure changes in light properties (such as absorbance, fluorescence, reflectance, or refractive index) that occur when the bio receptor binds to the analyse. This change in light properties is detected by optical instruments.^7,8

Fig.6. Elements of a biosensor.

Types of Optical Measurements:

Absorbance/Transmittance: Changes in light absorbance or transmission due to binding events.

Fluorescence: Emission of light when an analyse or probe molecule is excited by a light source.

Surface Plasmon Resonance (SPR): Measures the change in refractive index at the surface of a sensor when bio molecular interactions occur.

Resonance Light Scattering (RLS): Measures scattering of light caused by molecular interactions.

Applications: Optical biosensors are widely used in diagnostics (e.g., detecting specific biomarkers), environmental monitoring, and drug discovery.¹²

3 Mass-based Transducers:

In biosensors detect changes in mass as a result of the interaction between a bio receptor and a target analyse. These types of transducers are highly sensitive because even minute changes in mass can be detected. The principle behind these transducers is that the binding of the analyse to the bio receptor causes a shift in the system's mass, which can be measured.^[14]

Fig.7. Mass based transducer.

Types of Mass-Based Transducers:

1. Piezoelectric Biosensors

Principle:

Based on the piezoelectric phenomenon, which occurs when a material produces an electrical charge in reaction to mechanical stress, piezoelectric biosensors work. In a piezoelectric crystal, the frequency shifts when the mass of the analyse attaches to the bio receptor. The change in mass is directly correlated with this shift in frequency. Measurement: Variations in the piezoelectric material's resonance frequency are detected by the sensor. The frequency shift increases as the mass that adheres to the sensor surface increases.^[15]

Fig.8.Model of Piezoelectric Biosensors.

Applications:

Commonly used for detecting biomolecules, pathogens, and environmental contaminants, as well as for medical diagnostics and toxin detection.^7,8

Advantages of Mass-Based Transducers:

High Sensitivity: Mass-based transducers can detect extremely small changes in mass, making them very sensitive to low concentrations of analyses.¹⁶

Label-Free Detection: These sensors often do not require the use of labels or secondary reagents, as the binding event itself provides the signal.²⁴

Real-Time Monitoring: Mass-based transducers provide real-time detection, allowing for immediate feedback about the presence and quantity of the analyse.¹⁶

Applications:

· Medical diagnostics: Detecting specific biomarkers or pathogens in blood, saliva, or urine.

· Environmental monitoring: Identifying pollutants or toxins in water, air, or soil.

· Food safety: Detecting contaminants or pathogens in food products.

· Biotechnology research: Measuring interactions in drug development or enzyme activity.¹⁸

2. Electrochemical Biosensor:

An analytical tool known as an electrochemical (EC) biosensor is able to identify a particular biological molecule on an electrode and use electronic transduction to convert the biomolecule's presence into a detectable output signal. Because of their short detection times, ease of use, affordability, and portability, electrochemical biosensors are among the most widely used detection techniques for identifying a wide range of illnesses. They also have a lot of potential for point-of-care (POC) diagnostic applications Consequently, a number of electrochemical biosensors, such as Volta metric/ampere metric biosensors biosensors potentiometric biosensors and field-effect transistor (FET) based biosensors have been investigated for use in the creation of POC diagnostic platforms²⁰

Types of Electrochemical Biosensor:

Biosensor Amperometry:

An ampere metric biosensor is a standalone integrated instrument that provides precise quantitative analytical data depending on the amount of current generated by the oxidation. These biosensors often feature sensitivities, energy ranges, and reaction times that are similar to those of potentiometric biosensors. The "Clark oxygen" electrode is used infrequently in the basic ampere metric biosensor.²⁰

Fig.9. Schematic Diagram of Amperometry.

The redox reaction takes place at the working electrode, which is usually composed of carbon, platinum, or gold.

1. Bio recognition Element: Usually an enzyme that interacts particularly with the target, such as glucose oxidase for glucose sensors.

2. Electrolyte Solution: Offers the conduit for electron transmission and ion mobility.

3. Reference Electrode: Preserves a steady potential to guarantee precise current detection. The fifth electrode completes the circuit and makes it easier for electrons to move.²⁰

Amperometry Biosensor Examples:

1. Glucose oxidase, which catalyses glucose oxidation and produces electrons that are sensed as current, is the basis for glucose biosensors (such as those used in diabetes monitoring). Lactate biosensors are employed in critical care and sports medicine.²¹

2. Neurotransmitter sensors: Used in neurological research to identify dopamine, serotonin, and other chemicals.²²

Fig.10.Flow chart of Biosensors Principle.

Biosensor Principle:

Biosensors use biological recognition components (such as enzymes or antibodies) to identify particular analyses and translate the biological reaction into a signal that can be measured, either optically or electrically.²³

Analyse:

The particular material that the biosensor is intended to identify and quantify is known as the analyse. The detectable electrical response is produced when it binds to the biological material to form a bound analyser. In certain situations, the analyse may undergo a transformation that releases heat, gas (oxygen), electrons, or hydrogen ions.²³

Bio receptor:

The biological element that precisely binds to or interacts with the analyse is known as a bio receptor. Examples of these include enzymes, antibodies, and DNA. An example of a biological It facilitates the transmission of signals. It regulates the channels in the membrane. Additionally, it has a role in immunotherapy and immunological responses. Cell metabolisms such as growth, division, and death are induced by it. The foundation of biosensors that identify and measure biological molecules is a molecule that precisely detects and binds to a target, such as an enzyme, antibody, or nucleic acid.²⁴

Fig .11. Key components of bio receptor.

Molecular Recognition:

Transducer:

The unique interaction between two or more molecules that show molecular complementarity through non covalent bonding, such as metal coordination, hydrogen bonding, van dar Waals forces, hydrophobic forces, π–π interactions, and/or electrostatic effects, is known as molecular recognition.²⁴

Data Recording and Display:

For the purposes of detection and analysis, a transducer is a part that transforms the biological signal which results from the interaction between a bio receptor into a quantifiable signal, such as electrical, optical, or thermal. DNA-based memory biosensors can capture analogous data about chemical exposure by converting various population DNA fractions to the ON state. Wearable biosensors can provide personalised health solutions and real-time vital sign monitoring. Implantable biosensors can monitor physiological parameters over an extended period of time.²⁴

Obstacles and restrictions:

1. Sensitivity and Specificity: Increasing biosensor sensitivity and specificity.

2. Cost and accessibility: Increasing the affordability and availability of biosensors.

3. Regulatory Frameworks: Establishing legal frameworks for the development and implementation of biosensors.

4. Data Analysis and Interpretation: Developing methods and algorithms for this procedure.

5. Public Acceptance: Addressing public concerns and encouraging biosensor adoption.^[25]

Possible Uses:

1. Cancer Diagnosis: Biosensors for monitoring and early cancer diagnosis.²⁶

2. Diabetes Management: Continuous glucose monitoring using biosensors.²⁷

3. Neurological Disorders: Parkinson's disease and other neurological conditions can be detected and tracked with biosensors.²⁸

4. Infectious Diseases: Biosensors to identify infectious diseases like influenza and TB.²⁸

5. Biosensors for identifying pollutants and toxins in soil, water, and air are known as toxicity detectors.²⁹

Fig.12.Bio sensing chips for cancer.

CONCLUSIONS:

In order to successfully treat patients, it is basically vital to identify and diagnose a variety of human diseases early in their progression. To properly detect the disorders, it is crucial to create straightforward, sensitive, and reasonably priced diagnostic instruments like biosensors. Biosensors have a wide range of medical applications that benefit physicians and patients for a number of reasons, including disease reviews, clinical care, sickness control, preventive therapy, and patient health information. Nano materials have demonstrated broad applications in the creation of biosensors in recent years. The primary objective of clinical medicine is to classify patients according to easily implemented biosensors. Most people think that biosensors enable personalised care, which presents a fresh perspective on modern medical practice. This strategy has a significant impact on healthcare, offering a wide range of therapeutic and diagnostic medical treatments. In this way, collaboration among biosensors and scientific and technological advancements might result in a wider range of products, services, and facilities. This technology will address a number of issues in the medical field.

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Received on 26.03.2025 Revised on 15.04.2025

Accepted on 30.04.2025 Published on 15.05.2025

Available online from May 17, 2025

Research J. Science and Tech. 2025; 17(2):167-176.

DOI: 10.52711/2349-2988.2025.00024

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