APPLICATIONS OF BIOSENSORS IN CLINICAL BIOCHEMISTRY

Dr. Rohini KarunakaranAssociate Professor, Unit of Biochemistry

Preclinical CoordinatorActing Head – Medical Education Unit

Faculty of MedicineAIMST University

Professor Leland C Clark Jnr 1918–2005

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FATHER OF THE BIOSENSOR

Invented Clark OxygenElectrode - Pivotal device thatallows real time monitoring ofpatients blood oxygen levels

BIOSENSOR

A biosensor is an analytical device, whichcomprises of a detects, transmit andrecord the information regarding thephysiological, biochemical change or thepresence of a specific analyte (a chemicalor biological substance that needs to bemeasured) by producing a signalproportional to the concentration of thetarget analyte.

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Analyte

Biosensor

Bio element Transducer

Electrical Signal

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COMPONENTS OF A BIOSENSOR

TARGET ANALYTE

BIORECEPTOR

TRANSDUCER

AMPLIFIER

SIGNAL PROCESSER

RECORDING & DISPLAY

is the specific molecule that is detected by the biosensor

is the biological particle that binds with the target analyte and undergoes conformation

can convert the bioreceptor response from the analyte into a electric, measurable signal.

magnifies the signal manifold from the transducer to make it more noticeable and easier to analyse and interpret.

filters the intensified signal and obtains the proper signal by cancelling noise.

visually represents the data to the ones who analyse and use the information to find solutions to problems.

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VARIOUS COMPONENTS OF A BIOSENSOR

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TYPES OF BIOSENSOR

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CHARACTERISTICS OF BIOSENSOR

SENSITIVITY The ability of a biosensor to measure small variations of the concentration of the target analyte

SELECTIVITY

LINEARITY

RESPONSE TIME

PRECISION

ACCURACY

Chemicals Interference must be minimised forobtaining the correct result.

Linearity of the sensor should be high for thedetection of high substrate concentration.

Time necessary for having 95% of the responseThe closeness of agreement between independent measurements on the same sample

The closeness of the agreement between the biosensor measured value (concentration) and the true value the analyte in a test sample

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ADVANTAGES

Highly specific

Extremely fast response time

Continuous measurement

Small sample size with minimal preparation required

Portable, Easy-to-use

Cheaper than current technologies

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APPLICATIONS OF BIOSENSORS

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APPLICATIONS OF BIOSENSORS IN CLINICAL BIOCHEMISTRY

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Biosensor & chronic diseases Diabetes mellitus Prevalence of diabetes Nanotechnology Glucose monitoring techniquesNano biosensorFluorescent polymeric nano sensorQuantum dotsNanorobots

Glucose biosensor

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CHRONIC DISEASES

Major chronic disease are cancer, asthma,arthritis, diabetes, COPD, hepatitis, HIV/AIDSetc. Nanotechnology is the field that has potentialfor early diagnostic & advancement intreatment of Diabetes mellitus. It is one of the worlds leading health carecrisis.

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DIABETES MELLITUSDiabetes mellitus is a disorder that is characterized by change inlevel of blood sugar (glucose) resulting from defects in insulinproduction, insulin action or both.

Around 150 millions are affected from this multifactorialpolygenic disease and number is going to increase in comingfuture.

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TYPES OF DIABETES MELLITUS

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DIABETES MELLITUS

Goal of diabetes treatment is to control blood glucose level and prevent diabetes complications.Type 1 diabetic must take insulin (oral insulin) to control diabetesType 2 diabetic may be able to control blood glucose by diet adjustment and more exercises

In long term need medication(insulin) to control BGLRequire constant monitoring of glucose level to maintain appropriate glucose levelBlood glucose level in the body are dynamic.

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MEASUREMENT OF BLOOD GLUCOSE

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MEASUREMENT OF BLOOD GLUCOSE

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CONDUCTOMETRIC UREA BIOSENSOR

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GENE CHIP LAYOUT

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IMMUNOSENSORS

When antibodies are used as a reagent torecognize, bind and detect target analytes

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GLUCOWATCH

‘non-invasive’ transcutaneous glucose measurementReverse iontophoresis principle

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GLUCOSE MONITORING TECHNIQUES

Nanotechnology had contributed a lot in the field of glucose monitoring and diabetes managementSome of the techniques are:-1) Nano scale biosensors or nano biosensors2) Fluorescent polymeric biosensors or “Smart

tattoo”3) Quantum dots4) Nanorobots

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NANOTECHNOLOGY

Nanotechnology

1st sensors are designed using macro-micro scale

components

2nd Nanofabrication technique generate glucose sensors that are nanoscale in

dimension

NANO BIOSENSORWorks on the principle of “electro chemical biosensors”

Small size High surface/volume ratioEnhanced optical propertiesFaster response & improved catalytic activityMore efficient electron transfer from enzyme to electrodeEg:-Nano biosensors based on the property of fluoresence

signals such as FRET-(Forster resonance energy transfer).

NANO BIOSENSOR - ADVANTAGES

It involves biosensing through skin rather than havingelectrode system implanted. In this glucose binding protein (boronic acid derivative)

are incorporated on micro surface layer through layer bylayer assembly of nano film to encapsulate thecomponent.Eg:- Polyethylene glycol The fluorescence property change in response to BGL &

this change can be noted based on optical interrogationthrough skin.

FLUORESCENT POLYMERIC NANOSENSOR OR “SMART TATTOO”

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“SMART TATTOO”

Smart tattoo are implanted into the skin like regular tattoo but need to be replaced on time scale from weeks to months Offer ability for continuous monitoring through skin

with a less invasive approachAdvantages Reduce the need to take blood sample Data collected in a more continuous manner Avoid complication of implanted devices

“SMART TATTOO”

Quantum dots are the colloidal semiconductor nano crystals of a few nanometers in diameter their size& shape controlled during synthesisSynthesized from atom of group II-VI or III-V of periodic

tableSuch as calcium telluride or cadmium selinium forming

nano particles with florescent characteristics

QUANTUM DOTS

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QUANTUM DOTS

AdvantagesAllows rapid optical detection of BGLHave ideal long term implantation (i.e. they will not

photobleach over time)

DisadvantagesFluorescent sensor based on quantum dots will be more

expensive than current electro-chemical sensor. Implantation into body requires stringent toxicity testing.

QUANTUM DOTS

Nanorobot is a tiny machine designed to performspecific task with a precision at nanoscale dimensionsof few nanometers (nm) or less.

It work at atomic, molecular or cellular level toperform task in medical & industrial field

NANOROBOTS

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NANOROBOTS

Advantages Has no side effectsOperate freely inside body along blood stream It operates at specific site only

Disadvantages Initial design cost is very highNanorobot design is very complicated

NANOROBOTS

Finger stick Testing

Most common method to monitor blood glucoseProcedure:- Drop of blood is obtained with lancet Blood sample placed on test strip Test strip inserted in glucose meter to display BGLSome diabetics may have to perform

testing four or more times daily

COMMERCIALLY USED GLUCOSE BIOSENSOR

Sub dermal implants

Measures glucose in skin fluids by implanting on skin. Sensors life span 72 hours

Contact lens surface is embedded with sensor & microchip.Measure glucose in tear fluid eye

Smart contact lens

Source-Google contact lens

Source RTS, Medtronic Inc

Based on ultrasonic, electromagnetic & heat capacitySpot measurement on ear clipSensor life span (6 months)

GlucoTrack (Integrity application)

Symphony (echo therapeutics)

Advanced micro abrasion system Enhances the flow of interstitial fluid & molecules across

skin to transdermal surface Sensor life span 24-48 hours

There is a great need to bring synergy among R&Dinstitutions and Government, Industrial houses that leads tosmooth transmission of technology.The level of sophistication, awareness, cost, reliability,

availability and marketing are all factors involved in deciding,whether biosensors would become popular in near future.Promising approach to medical diagnostics by patients or in

doctors officesOther important applications: pathogens, disease

biomarkers, DNA, peroxide, etc.Method of choice for blood glucose in diabeticsRapid diagnostics may lead to more timely and effective

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CONCLUSION

A Biosensor is a analytical device convert biological responseto electrical signalDiabetes mellitus is disease occur due to insufficient insulin

production or action or bothNanotechnology provides potential for early diagnosis of

diabetesMain glucose monitoring techniques are Nano biosensor,

“Smart tattoo”, Quantum dots & Nano robots.Commercially used sensors are Accu check , Smart contact

lens, gluco track etc.Progress in this field is rapid but ultimate goal for accurate,

continuous glucose monitoring in patient is yet to be achieved

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CONCLUSION

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FUTURE CHALLENGES/DIRECTIONS

The most important future challenges for biosensorsconsist of: size, remote operation, reliability,sensitivity, accuracy, sample handling, telemetryand range of analytes

The multidisciplinary arena of expertise necessaryfor the development of biosensors can be sustainedby the collaboration of many areas of academia andindustry. Though the result is a slow process butmost probably the only realistic path to successfulfuture advances in biosensor technology.

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REFERENCES

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