shows the historical overview of biosensors in the period 1970–1992. Ever since the development of the i-STAT sensor, remarkable progress has been achieved in the field of biosensors. The field is now a multidisciplinary area of research that bridges the principles of basic sciences (physics, chemistry and biology) with fundamentals of micro/nano-technology, electronics and applicatory medicine. The database ‘Web of Science’ has indexed over 84000 reports on the topic of ‘biosensors’ from 2005 to 2015.

1. Biosensors and bioelectronics
Background
Biosensors
The historyof biosensorsdatesbacktoas earlyas 1906 whenM. Cremer demonstratedthatthe
concentrationof an acidin a liquidisproportionaltothe electricpotential thatarisesbetweenpartsof
the fluidlocatedonopposite sidesof aglassmembrane.However,itwasonlyin1909 that the concept
of pH (hydrogenionconcentration) wasintroducedby SorenPederLauritz Sorensenandan electrode
for pH measurementswasrealizedinthe year1922 by W.S.Hughes. Between1909 and 1922, Griffin
and Nelsonfirstdemonstratedimmobilizationof the enzyme invertaseonaluminumhydroxide and
charcoal.The first‘true’biosensorwasdevelopedby LelandC.Clark, Jr in 1956 for oxygendetection.He
isknownas the ‘fatherof biosensors’andhisinventionof the oxygenelectrode bearshisname: ‘Clark
electrode’.The demonstrationof anamperometryenzymeelectrode forthe detectionof glucose by
Leland Clark in1962 wasfollowedbythe discoveryof the firstpotentiometricbiosensortodetecturea
in1969 by Guilbaultand Montalvo,Jr. Eventuallyin1975 the firstcommercial biosensorwasdeveloped
by YellowSpringInstruments(YSI).Table 1 showsthe historical overview of biosensorsinthe period
1970–1992. Eversince the developmentof the i-STATsensor,remarkableprogresshasbeenachievedin
the fieldof biosensors.The fieldisnowamultidisciplinaryareaof researchthatbridgesthe principlesof
basicsciences(physics,chemistryandbiology) withfundamentalsof micro/nano-technology,electronics
and applicatorymedicine.The database ‘Webof Science’hasindexedover84000 reportson the topic of
‘biosensors’from2005 to 2015.
Table 1.
Importantcornerstonesinthe developmentof biosensorsduringthe period1970–1992
 1970 Discoveryof ion-sensitivefield-effecttransistor(ISFET) byBergveld
 1975 Fiber-opticbiosensorforcarbondioxide andoxygendetectionbyLubbersandOpitz
 1975 Firstcommercial biosensorforglucose detectionbyYSI
 1975 Firstmicrobe-basedimmunosensorbySuzuki etal.[10]
 1982 Fiber-opticbiosensorforglucose detectionbySchultz
 1983 Surface plasmonresonance (SPR) immunosensorby Liedbergetal.
 1984 Firstmediated amperometrybiosensor:ferroceneusedwithglucose oxidase forglucose
detection
 1990 SPR-basedbiosensorbyPharmaciaBiacore
 1992 Handheldbloodbiosensorby I-STAT

2. bioelectronics
The firstknownstudyof bioelectronicstookplace inthe 18th century,whenscientist Luigi Galvani
appliedavoltage toa pair of detachedfroglegs.The legsmoved,sparkingthe genesisof bioelectronics.
Electronicstechnologyhasbeenappliedtobiologyandmedicine since the pacemakerwasinventedand
withthe medical imagingindustry.In2009, a surveyof publicationsusingthe termintitle orabstract
suggestedthatthe centerof activitywasinEurope (43 percent),followedbyAsia(23 percent) andthe
UnitedStates(20 percent).
Introduction
Biosensors
A biosensor is a device that measures biological or chemical reactions by generating signals proportional to the
concentration of an analyte in the reaction. Biosensors areemployed in applicationssuch asdiseasemonitoring,
drug discovery,and detection of pollutants,disease-causingmicro-organisms and markers thatare indicatorsof a
diseasein bodily fluids(blood,urine,saliva,sweat).A typical biosensor isrepresented in Figure1; itconsists of the
followingcomponents.
 Analyte: A substanceof interest that needs detection. For instance,glucoseis an ‘analyte’in a biosensor
designed to detect glucose.
 Bioreceptor: A moleculethat specifically recognizes theanalyteis known as a bioreceptor. Enzymes, cells,
aptamers, deoxyribonucleic acid (DNA) and antibodies aresome examples of bioreceptors.The process of
signal generation (in the form of light,heat, pH, chargeor mass change, etc.) upon interaction of the
bioreceptor with the analyteis termed bio-recognition.
 Transducer: The transducer is an element that converts one form of energy into another. In a biosensor
the role of the transducer is to convert the bio-recognition event into a measurablesignal.This process of
energy conversion is known as signalization.Mosttransducers produceeither optical or electrical signals
that are usually proportional to the amount of analyte–bioreceptor interactions.
 Electronics: This is the partof a biosensor thatprocesses the transduced signal and prepares itfor display.
It consists of complex electronic circuitry thatperforms signal conditioningsuch as amplification and
conversion of signals fromanalogueinto the digital form.The processed signalsarethen quantified by the
display unitof the biosensor.
 Display: The display consists of a user interpretation system such as the liquid crystal display of a
computer or a direct printer that generates numbers or curves understandableby the user. This part
often consists of a combination of hardwareand software that generates results of the biosensor in a
user-friendly manner. The output signal on the display can benumeric, graphic,tabular or an image,
depending on the requirements of the end user.

3. Bioelectronics
At the firstC.E.C. Workshop,in Brussels in November 1991,bioelectronics was defined as 'the use of biological
materials and biological architectures for information processing systems and new devices'. Bioelectronics,
specifically bio-molecularelectronics,were described as 'the research and development of bio-inspired (i.e.self-
assembly) inorganicand organic materialsand of bio-inspired (i.e.massiveparallelism) hardwarearchitectures for
the implementation of new information processingsystems,sensors and actuators,and for molecular
manufacturingdown to the atomic scale'.The National Instituteof Standards and Technology (NIST), an agency of
the United States Department of Commerce, defined bioelectronics in a 2009 report as "the disciplineresulting
from the convergence of biology and electronics".
Sources for information aboutthe field includethe Institute of Electrical and ElectronicsEngineers (IEEE) with its
Elsevier journal Biosensors and Bioelectronicspublished since1990.The journal describes the scope of
bioelectronics as seekingto: "... exploit biology in conjunction with electronics in a wider context encompassing,
for example, biological fuel cells, bionics and biomaterials for information processing, information storage,
electronic components and actuators. A key aspect is the interface between biological materials and micro and
nano-electronics.