All about Biosensors- A Review

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All about Biosensors- A Review

1 School of Electronics and Telecommunication, MIT World Peace University, Pune 411038, Maharashtra, India

2 School of Mechanical Engineering, MIT World Peace University, Pune 411038, Maharashtra, India

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Abstract Sensors are one of the most important inventionsinengineeringhistory,andbiosensorsareoneof them.Biosensorshavebeenunderdevelopmentforover35 years,becomingmoreprominentinthelast15years.Silicon Nanowires, for example, has paved the way for a flood of newsignaltransductionmethodsinbiosensors,illustrating thefield'sadvancement.Recently,NASAhasbeendeveloping better physiologic sensor and biotelemetry system technologies,to continuously assess basic physiological indicatorsinunrestrainedspacebeings,suchasheartrate, blood pH, and body temperature, which is a challenging problemtosolve.

Approximately20to25yearsago,biosensorswereoneof themysterioustopicsinengineeringastheyconnectedtwo differentfields(electronicandbiology).Butnow,fromthe detectionofCovid 19inmedicalsciencetothedetectionof microorganismsinspacetechnology,biosensorsareusedon alargescaleandhavebecomethemostpopularchoicefor manufacturers. In this review, we will encounter every prospect,application,andtypeofbiosensor.

1. Introduction

Leland C. Clark, Jr, also known as "Father of Biosensors", discoveredbiosensorsin1954.LelandC.Clarkcreatedthe first biosensor for the detection of oxygen. "CLARK ELECTRODE"isthenameoftheoxygenelectrodethatwas invented by him. This electrode was later named as a biosensor. Astimepassed,biosensorshavebecomepopular and in today's era, it is used everywhere in the industry. Various fields like very large integrated circuits (VSLI), electronics, physics, biotechnology, mechanical, etc. are workingtogethertomakethissensormoreandmoreviable [1][2][3].

● What are Biosensors?

You will find various definitions based on the field of application.Butinsimplewords,wecansaythat"Biosensors aredevicesthatareusedtomeasuretheconcentrationofthe analyte(analytecanbeanybiologicalelementdependingon the application. Examples of analytes for glucometer are Blood and sugar). These devices can convert biological responses(analyteresponse)intoanelectronicsignal"[1].A biosensor uses a unique biological recognition element

whose characteristic can change when it binds to that particular element. This helps in monitoring its environmental and physical compounds. Biosensors are simple, quick, low cost, sensitive, and highly selective. Surfacechemistryadvancementshaveprovidedavarietyof newwaysfordevelopingdetectorrecognitionsystems.The combination of intelligence by various fields will help to speed up the development of biosensors and help to transformbiologicaldisciplines[3][5].Theperformanceof thebiosensorisaffectedbytheoptimizationofitsstaticand dynamiccharacteristics.

Theattributeorparameterstoconsiderare:

1. Selectivity: When biosensors are constructed, the selectionofthecorrectbioreactorplaysanimportant role. A bioreceptor's selectivity refers to its capacity toidentifyasingleelementinthepresenceofvarious fillersandpollutantsinasample.

2. Lifeofa sensor: Theaveragelifeofa biosensoris threemonths(90days).

3. Stability: Stability is the accuracy maintained by the device in the presence of environmental disturbance. More stability causes a small error and preciseresults.

4. Accuracy: Sensor's accuracy matters the most. As for biosensors, the accuracy rate is almost 92% to 95%.

5. Detection limit: The limit of an instrument that fails to recognize the minimum concentration of an analyte. Mostly estimated from the mean and standarddeviationofthesolutionorsamplepresent.

Biosensors are manufactured by considering these parameters.[5]

I. Working

Ifyouobserveadevice,youwillnoticethatabiosensorare composedofthreemainparts:

● Recognitionofanalyte.

● Convertingcollecteddatatosignal.

● Readingthesignal.

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Key words: Biosensors, Types of Biosensors, Application of Biosensor

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In simple words, a biosensor consists of a biological componentthathelpsthedevicerecognizeorcommunicate withtheanalyte.Thiscommunicationproducesaphysicalor chemicalresponsewhichisfurthercollectedbyatransducer. These changes can be magnetic, electrochemical, optical, thermal,etc.Withthisdata,thetransducerconvertsitinto anelectricalsignal.Thesesignalsarethenpassedontothe electronic(amplifier,processor)toconvertitintoareadable form. Finally, after all these processes the output is displayed.[2][5][6]

II. Types of Biosensors

Modern multidisciplinary bioscience techniques involving bioengineering, electrical and electronics engineering, mechanical engineering, biomedical engineering, etc have opened the way for the development of biosensors for a variety of detection methods with a broad array of applications in the field of medical and environmental research.Therearemanybiosensorsinventedtodatebased on the transducer and the type of biological material (Bioreceptors) used. We will discuss the types in detail.[6][7][8]

A. Electrochemical Biosensors:

Many electrochemical biosensors have been created and presentedinrecentyearsfortheidentificationofmultiple medicalconditions based on specific indicators, utilizing their properties which were discussed in the previous section. Electrochemical Biosensors are further divided based on the electrochemical parameter measured. [9][10][2]

● Amperometric Biosensor: As we have previously discussed the invention of "CLARK ELECTRODE'', in 1962 (nearlytenyearslater)heusedthesameglucoseoxidized enzymeandreverseditspolarityoftheelectrodetocreate the first Amperometric Biosensor. Amperometric biosensors work on the moment of electrons produced in a redox reaction. The glucometer is probably the most well known amperometric biosensor. This is one of the most popular devices that is used to check glucose levels in the blood. At the bottom of the biosensor, the glucose oxidase enzyme is immobilized. Oxygen is released when glucose combines with the glucose oxidase enzyme and passes through an oxygen permeable membrane. It then reacts with the platinum electrode, resulting in electron flow and current flow. A voltage will be created from this current. With the assistance of an amplifier, the voltage will be amplified, and the glucose level in the sample will bedisplayed.

● Potentiometric Biosensor: Potentiometric biosensor in simple terms converts mechanical displacement into voltage difference. These biosensors play a major role in Clinical chemistry. The core principle of this biosensor is that while the length of a variable is

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variedataconstantdistance,thecorrespondingresistance will be experiencing some changes. It must have a steady current running through it as a requirement. Potentiometric biosensor makes use of ion electrodes to transducebiologicalresponseinelectricalform.

● Conductive Biosensor: When a constant potential is supplied between a reference electrode and a polymer modified electrode, a change in electrical conductivity or resistivityisdetectedagainsttheanalyteconcentration in conductometric conducting polymer based biosensors. To boost the sensor's sensitivity, the conducting polymer must be electrically efficient when charged (doped) and lowly conductive when neutral, resulting in a significant conductivity shift when the conducting polymer reacts withtheanalyte.

B. Thermometric Biosensors:

Thermal sensors and calorimetric biosensors are other names for these biosensors. The colorimetric biosensor is basedonthefactthatvariousbiologicalprocessesarelinked tothecreationofheat.Acalorimetricbiosensormeasures the amount of heat produced during an enzyme process. Thermistors are used in most of these sensors to convert heat created or lost during the reaction into an electrical signal.Thereareseveraldrawbackstousingacalorimetry sensor, including the need for an insulated jacket to minimize heat loss by radiation, which makes the device large.Also,thesensitivityofthecalorimetricsensorislow. Toquantifyorestimateserumcholesterol,athermometric biosensorisutilized.Whencholesterolisoxidizedusingthe enzymecholesteroloxidize,heatisgenerated,whichmaybe estimated. These biosensors may also be used to test for glucose,urea,uricacid,andpenicillinG.

C. Optical Biosensor

Theopticalbiosensorworksonthepremiseoflightoutput during a reaction or light absorbed by the difference in reactantandproductconcentration.Let'shavealookatan opticalbiosensorasanexample.Considerabiosensorused inthefoodindustriestodeterminewhetherafoodproduct is polluted at the time of consumption. A small biosensor strip will be inserted inside the food packet, and if it is contaminated with bacteria, it will be lighted [10]. This is donewiththehelpofanenzymecalledluciferase.Luciferase enzyme is obtained from fireflies. When the luciferase enzymeinteractswiththebacterialcell,itislysedandthe ATPcontentisreleased.Thebiosensorwillbelightedand luminancewillbecreatedwhenATPreactswiththeluciferin includedinit.Bydoingso,wecandeterminewhetherornot foodispolluted.Opticalbiosensorsarethemostwidelyused biosensors in healthcare, environmental science, and the biotechnologyindustry.

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D. Piezoelectric sensors

Becausetheyfunctionwiththeideaofsound,piezoelectric biosensorsarealsoknownasacousticsensors.Positiveand negative charge crystals have a certain frequency of vibration. Electronic equipment can detect the resonance frequency. There are certain disadvantages to using a piezoelectric sensor. For example, it is difficult to use a biosensortodeterminethematerialinasolutionsincethe crystal may stop oscillating entirely in a viscous liquid. Piezoelectricceramicsmayadapttoavarietyofshapeswhile maintaining their fundamental characteristics because of theirgreatelasticity,Piezoelectricbiosensorsoffera wide range of applications. For example, in a microphone, the soundsignalisturnedintoanelectricalsignal,whichisthen amplified to provide a louder sound. In medical science, piezoelectric is used in ultrasonic equipment, disposable monitoring,andfetalheartmonitors.

E. Whole-Cell Biosensors:

Microbial Biosensor is another name for whole cell biosensor.Thecompletecellisimmobilizedonthesurfaceof thetransducerinawhole cellbiosensor.Itdoesn'tmatterif thecellisaliveordead.Inamultistepprocessoraprocess thatrequiresacofactor,thesesensorsareuseful.Whole cell biosensors are less expensive and have a longer lifespan. When compared to an isolated enzyme, they are less susceptibletochangesinpHandtemperature.

F. Immuno Biosensor:

Immuno biosensors work by combining immunological distinctiveness with measurements taken by an amperometric or potentiometric biosensor. The relative concentrationsoflabeledandunlabelledantigensaffectthe activity of enzymes linked to immunosensor. The enzyme activitycanbeusedtodeterminetheconcentrationofthe enabledantigen.

III. APPLICATIONS

A. Environmental Science:

Our environment has acquired different pollutants as a resultofrecentindustrializationandmodernization.Heavy metals,herbicides,complexhydrocarbons,andseveralother substancesareamongthem.However,numerousbiosensors have been developed solely to address environmental issues.[11]

● Heavy metal Detection: As we all know the environment contains both vital and hazardous metals. Toxic heavy metal accumulation in humans may cause a range of major health problems, including damage to the liver, kidneys, brain system, and even our reproductive system. An enzyme can respond to a variety of heavy metals, but it won't be able to respond to all of the heavy

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metals in the environment [3]. As a result, they are only suitable for the development of specialized heavy metals. However, if we want to construct a biosensor for toxicity and analysis, we can use a variety of enzymes. This is where enzyme basedproductscomeinhandy.Biosensors basedonenzymescanbeusedinthissituation.

● Pesticide Detection: We all know the disadvantages of using pesticides as they can be dangerous to human health. If farmers are exposed to pesticides without using any suitable protective equipment, they may develop major long term health problems such as cancer. It can also cause our healthy environments to go out of balance. Pesticide detection is carriedoutusinganamperometricbiosensorthatisatype ofelectrochemicalbiosensor.[13][15]

● BOD (Biochemical oxygen demand) biosensors: BOD is the quantity of oxygen required by aerobic living organisms in water to break down organic molecules presentinaparticularwatersampleduringaspecifictime and at a certain temperature.The elements utilized to determine BOD are primarily pure cultures of a combination of known microorganisms. Because yeast is resistant to unfavorable environmental variables, it is the bestbiologicalagentforBODbiosensors.Incomparisonto pure cultures, microbial consortia are employed to broaden the range of oxidized substrates. To increase substratespecificityandensurethelong termfunctioning of the biosensor, Trichosporon Cuteneum and Bacillus licheniformis are commonly utilized combined. The use of a biochemical oxygen demand (BOD) biosensor is to improve biological molecule detectionthat contaminates water bodies andcause dangerous diseases that can lead todeath.

B. Medical Science:

● Cancer detection: Cancer is the biggest cause of mortality in the world, and its incidence has increased. Each year, 12.7 million people are diagnosed with cancer, and7.6milliondiefromit.However,datasuggeststhat30 to40% of these deaths can be avoided, and one thirdcan be cured if diagnosed and treated early [6]. For breast cancer, the survival rate is 98% if discovered early [10]. The biosensor, which operates on the idea of surface plasmon resonance, or SPR, is a device that aids in the early detection of cancer. Biosensors can transform biological reactions into electrical signals, as we know [14].Tumorcells,inthecaseofcancerdetection,serveas analytes. In biosensors, cancer cells can be identified by detecting the amount of a specific protein released or expressedbytumorcells.Wecandetermineifatumorcell is malignant or non cancerous by collecting data from it.[15][16][11][12][13]

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● Wearable Biosensors: In the old days, patients used to have to go to the doctor to discuss their sugar levels, their weight if they had heart failure, or their breathing if they had COPD or asthma. However, today's patients have access to a wearable sensor that can be utilized at home to deliver all of their body's information with accuracy. During dangerous operations or even in a busy emergency department, patients can be monitored usingwirelesstechnology,andwearableBiosensorsplaya bigpart.[17]

● Covid 19 Detection: Covid 19 and other respiratory virus interactions are detected using biosensors. To detect the presence of the virus, these biosensors just required a saliva sample. Simply place a sample in the gadget, wait a few minutes, and the gadget willtellyouifyouareinfectedornot,aswellasthevalue of your antibody levels in your body [13][14]. While they are extremely accurate in the instance of covid 19, they may take some time to get a result. Biosensors were crucial in the detection of this pathogen as it is safe and easy to handle [18]. Further according to [18], a FET or a field effect transistor based biosensing device can be a promising way to detect viral or sensitive immunological diseases. This is because of the reason that these FET based biosensors use semiconductor materials like graphene etc and are highly sensitive which results in a veryquickdetectionofevenverysmallamountsofanalyte [18]. Graphene based FET biosensors are very responsive and can sense changes in the surroundings or on their surface, which provides a very good sensing environment and serves the purpose very well. Further [22] have developed FET biosensor to detect COVID 19, which has provedveryeffectiveasitprovidesaprompt,accurateand specificresponsetoSARS CoV2inthetestedsamples[22]. Withtechnologicalandindustrialadvancementaroundthe world, there is also a sharp rise in the emergence of new viruses such as the coronavirus, which are highly contagiousandhavethecapabilitytocauseamajorlossof life.Insuchsituations,biosensorshave been ofgreathelp duetotheirquickandaccurateresponses.Thustheyhave provedto bea steppingstonefordoctorsastheycanrely onbiosensorsfordiagnosisandthusplanthelineofaction tocurethedisease.

C. Food Technology

● Quality of Food: Food can degrade as a result of digestion in microbial development, and tracking such deviations over time might provide us with an overall estimate of food quality [1][4]. Biosensors enable smart and responsive packing for food product freshness monitoring, which plays a significant role in food science. Whenthebiosensorisnearfood,itmayevaluatereadings from signals obtained to determine the quantity and purity of the sample food. The outcome is shown on an LCD,and it is then possible toassess if the food is of high

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or low quality. Biosensors may be used in a range of situations, including hotels, private residences, and even small enterprises. This technology manages food chain monitoring without the need for human interference. (A buzzer linked to the sensor is used in some small experiments to support the blind and people with vision problemsindeterminingthefoodquality).

● Detectionofallergen:Foodallergiesarebecoming a serious public health and food safety problem worldwide. People who are allergic to certain foods have negative reactions. Because it's incurable, the best course of action is to avoid it. The demand for fast, accurate, and accurate technologies for tracking food allergens has grown throughout the world as the danger of hidden allergiesinfoodstuffhasgrown.themicrofluidicbiosensor canhelptodetecttheseallergenspresent inthefood.[15] Further according to [3], E coli is the most dangerous pathogen which is food borne. It causes extreme symptoms such as bloody diarrhea, hemorrhagic colitis etc. it is so deadly that it is one of the major reasons of food related deaths around the world. Traditional methodsto detect thispathogenarevery timeconsuming andinefficient.SinceE colihastheabilitytoconvertintoa non curable disease, it is very important to diagnose it well in time. Hence biosensors such as optical and electrochemicalbiosensorsweredevelopedtodiagnoseE coli.In2017,Zhangetal,developedabiosensor,whichisa multichannel SPR based biosensor, which was able to detect the pathogen in very less quantity as well,[3] thus provingtobealifesaver.

D. Market Analysis:

From2021to2030,thebiosensorsmarketisestimatedto increase at a CAGR (Compound annual growth rate) of approximately 8%, from USD 25.5billion in 2021 to USD 36.7billion[20].Thedevelopmentofnanotechnology based biosensors, considerable technological advances in recent years,growingneedforbiosensorsformonitoringglucose levelsindiabetespatients,surgingdemandforportableand easy to usedevices inthe COVID 19 pandemic, and increasing social programs toward medicaltherapies are some of the important primary drivers in the biosensors business(Biosensorsbasedonnanotechnologyarecreated of nanoparticles with diameters size less than 100 nanometers[18]. These biosensors are critical for understandinghowthebiosensingsystemworks).According totheWHO,approximately1.7billionpeopleweresuffering fromobesity in 2016, with almost 648.8million of them being overweight. This has boosted industry growth by increasingsalesofmonitoringandanalysisequipmentused forthemedicalsensorsinthehouseandhospitalsettings. During the projection timeframe, 2017 2024, the international demand for wearable sensors is expected to grow at a rapid rate [17]. Moreover, growing demand andacceptanceofhealthcareapplications,alongwithrising

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government expenditure, are some of the primary factors expected to drive the worldwide wearable biosensors marketovertheforecastperiod.[21]

Conclusion

Biosensorsarebecomingincreasinglypopularasaresultof theirnumeroususes.Thistechnologyisprogressingatthe samerateasdemand. Accordingtome,thescientistmust concentrateonthreemajorelementstoincreasethequality ofbiosensors:specificity,detectionlimit,anddetectiontime. Biosensors have a bright future ahead of them, with widespread applications in screening tests, food analysis, smartmanufacturing,andremotesensing.

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