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Bioelectronic Nanosensor Devices for Environmental and Biomedical Analysis

Risveden, Klas LU (2008)
Abstract (Swedish)
Popular Abstract in Swedish

Idag kan vi mäta mycket låga halter av gifter i t. ex. dricksvatten och livsmedel, bland annat

genom utvecklingen av nanosensorer. Sensorerna kan också använda's medicinskt, t. ex för att

väsentligt underlätta livet för diabetiker. Idag drabba's diabetespatienter ofta av nedsatt känsel

i fingrarna på grund av dagliga nålstick. Med hjälp av de nya sensorerna kan vi nu mäta så

låga halter och volymer av blodsocker att vi tror att det snart blir möjligt att ersätta blodprov

med prov från andra kroppsvätskor, t. ex ett salivprov.





Den unika nanosensorn som beskriv's i avhandlingen är baserad på... (More)
Popular Abstract in Swedish

Idag kan vi mäta mycket låga halter av gifter i t. ex. dricksvatten och livsmedel, bland annat

genom utvecklingen av nanosensorer. Sensorerna kan också använda's medicinskt, t. ex för att

väsentligt underlätta livet för diabetiker. Idag drabba's diabetespatienter ofta av nedsatt känsel

i fingrarna på grund av dagliga nålstick. Med hjälp av de nya sensorerna kan vi nu mäta så

låga halter och volymer av blodsocker att vi tror att det snart blir möjligt att ersätta blodprov

med prov från andra kroppsvätskor, t. ex ett salivprov.





Den unika nanosensorn som beskriv's i avhandlingen är baserad på jonkanalsfälteffekttransistorteknik

(RISFET = Regional Ion Sensitive Field Effect Transistor). I en RISFET-sensor

använd's ett elektriskt fält för att bilda en elektriskt ledande jonkanal i nanometerskala mellan

mätelektroderna. Bildningen av jonkanalen ökar sensorn's mätkänslighet.





För att skilja olika ämnen åt kan man använda enzymer. Ämnet som man vill analysera kan

antingen självt omvandla's med hjälp av ett enzym eller påverka ett enzym's förmåga att

omvandla ett annat ämne. Den enzymatiska omvandlingen av ämnet förändrar de elektriska

egenskaperna, bland annat den elektriska ledningsförmågan, ho's provlösningen. De elektriska

egenskaperna ho's provlösningen kan mäta's av sensorn med hög känslighet.





Genom att följa hur de elektriska egenskaperna ho's provet förändra's kan man alltså inte bara

ta reda på halten av ett specifikt provämne utan också få en uppfattning om ”hälsotillståndet”

ho's enzymet. En del av de gifter som vi kan stöta på i naturen, i dricksvatten eller i livsmedel

kommer från bekämpningsmedelsrester. I ett allvarligare scenario kan det gälla gifter som

avsiktligt spridit's ut (bioterrorism). Ett friskt enzym (acetylkolinestera's) har en hög

omvandlingshastighet av sitt naturliga substrat. Men om enzymet exponera's för gifter kan

enzymet påverka's kraftigt vilket kan registrera's av sensorn och utlösa en larmsignal.





Sensorn består av en liten platta, ett chip's, försedd med mätelektroder. Dessa ligger på en

isolator vilken täcker en ledande kiselbaserad platta. Vid mätning placera's en provdroppe på

chipset. Om man nu lägger en tillräckligt svag växelspänning mellan elektroderna kommer en

ytterst svag ström att flyta mellan elektroderna, varvid strömstyrkan beror på provet's

sammansättning. En elektrisk potential applicera's sedan mellan den ledande kiselbaserade

plattan och provdroppen, varvid ett elektriskt fält bilda's. Fältet koncentrerar provet's joner och

laddade partiklar till området mellan elektroderna vilket medför att den elektriska

ledningsförmågan markant ökar. Resultatet blir en betydligt starkare ström som sensorn kan

registrera.





En viktig aspekt ho's den nya sensorn är att strömmen mellan mätelektroderna lätt kan mäta's

med hjälp av en egentillverkad lågbrusig pikoampermeter i kombination med ett oscilloskop

och skräddarsydd programvara.





Tillverkningen av sensorchipsen har baserat's på konventionell mikro- och nanoprocessteknologi

och en serie chip's framställde's med varierande avstånd mellan mätelektroderna

(40 nm – 2500 nm). Tester visade att små elektrodavstånd gav en väsentligt högre

mätkänslighet än stora. Förutom betydelsen av korta elektrodavstånd för att få hög känslighet

är det många andra faktorer som spelar in, vilket också diskutera's i avhandlingen. För att ge

en fingervisning om den mätkänslighet som uppnått's kan nämna's att insektsgiftet karbofuran

kunde observera's i koncentrationer ner till ca 20 nanogram/liter det vill säga

0,000 000 02 gram/liter.





Som ett komplement till den RISFET-baserade nanosensorn har också ett system för

automatisk applicering av mätprover på chipsytan utvecklat's. Kombinationen lämpar sig för

kontinuerlig övervakning av gifter i dricksvatten.





Det skall påpeka's att de minsta chipsbaserade mätkretsarna som använt's här utnyttjar

komponenter som är 100 gånger mindre än bakterier. Nanotekniken tillåter också att man

bygger olika mätceller mycket tätt och där varje enskild mätcell mäter sitt ämne med hjälp av

ett specifikt enzym. Sålede's medger nanotekniken att man konstruerar behändiga

multisensorer som simultant kan mäta ett stort antal komponenter i ett prov.





En viktig aspekt i utvecklingsarbetet har varit att kunna karakterisera och vid behov felsöka

de nyutvecklade chipsen. Därvid har tekniker såsom atomkraftsmikroskopi och

svepelektronmikroskopi varit oumbärliga. (Less)
Abstract
A new type of Bioelectronic Nanosensor Device with potential applications in medicine,biotechnology and environmental analysis was designed. The nanosensor is based on RISFET (Regional Ion Sensitive Field Effect Transistor) technology. The design of the nanosensor

involves use of a set of nano-sized electrodes on the surface of a silicon chip, giving the chip the ability to sense extremely low concentrations of specific analytes by means of an amplifying process. Analyte ions (or enzymatically generated product ions of these) are

focused by a charged field to become concentrated in a narrow region – a conducting channel – located between two sensing electrodes. The focusing process leads to significant changes in... (More)
A new type of Bioelectronic Nanosensor Device with potential applications in medicine,biotechnology and environmental analysis was designed. The nanosensor is based on RISFET (Regional Ion Sensitive Field Effect Transistor) technology. The design of the nanosensor

involves use of a set of nano-sized electrodes on the surface of a silicon chip, giving the chip the ability to sense extremely low concentrations of specific analytes by means of an amplifying process. Analyte ions (or enzymatically generated product ions of these) are

focused by a charged field to become concentrated in a narrow region – a conducting channel – located between two sensing electrodes. The focusing process leads to significant changes in conductivity, increasing the level of the current between the sensing electrodes. The current, registered by a pico-ammeter produced in-house, is a measure of analyte concentration.



To achieve specificity, the RISFET nanosensor is provided with immobilized enzymes in the form of minicolumns within a flow system. Studies were conducted exploring possibilities of simplifying the system, improving its effectiveness and making it more compact. It appears

that the enzymes should best be moved to an area of the chip in the vicinity of the sensing electrodes, and that branched nanowire structures (nanotrees) be placed on the chip-surface area located between the sensing electrodes to serve as carriers of the enzymes. The nanotrees would ensure an adequate load of enzymes without either the focusing of the ions or the sensing ability being disturbed. Features of this sort are seen as being particularly important for future high-density RISFET nanosensor arrays.



The basic properties of the sensor were investigated using such analytes as glucose, gluconolactone, acetylcholine and carbofuran. Specificity was found to be achieved when the

enzymes glucose oxidase and acetylcholine esterase were employed. The inhibition of acetylcholine esterase by carbofuran was detectable down to about 20 ng/L. An automatic online biosensor unit for the neurotoxic organocarbamate carbofuran was constructed and was

found to work satisfactorily.



A number of chip configurations, involving use of different silicon technologies and different electrode arrangements, were designed and characterized. In addition, a study of a Quartz Crystal Microbalance (QCM) biometric sensor was carried out; the sensor surface was functionalized by use of molecularly imprinted nanoparticles specific for (R)- or (S)-propranolol. Frequent use was made in the work as a whole of Atomic Force Microscopy (AFM), Scanning Kelvin Probe Microscopy (SKM) and Scanning Electron Microscopy (SEM). The usefulness of multifunctional nanobiosensor array systems for the surveillance of liquids regarding the presence of many different toxic and biomedically relevant analytes, and in medical, environmental and biotechnological analyses generally is discussed. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Frank, Bier, Fraunhofer Institut für Biomedizinische Technik IBMT, Potsdam-Golm, Germany
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Regional Ion Sensitive Field Effect Transistor, Region Ion Sensitive Field Effect Transistor, RISFET, Conducting channel, Bioelectronic Nanosensor, Bioelectronic, Biosensor, Nanosensor, Chemical Sensor, Sensor, Semiconductor sensor, Single molecule trapping, Scaling, Protein trapping, Nanoelectronics, Lab-on-a-chip, pico-ammeter, Nanobiosensor, Sample Applicator, Sequential Batch Analysis, Sequential Batch Analysis System, SBAS, Nanowire, Branched nanowire structure, Nanotree, Nanorod, Nano processing, Micro processing, Electron Beam Lithography, EBL, UV-lithography, Molecular Imprinting, DUV-lithography, Moleculary Imprinted Polymers, MIP, Biomimetics, QCM, Biomimetic sensor, Quartz Crystal Microbalance, QCM-D, Nanoparticles, Acetylcholine esterase, Glucose oxidase, Glucose, Gluconolactone, Propranolol, Gluconate, Carbofuran, Neurotoxic, Environmental analysis, Biomedical Analysis, Biotechnology, Medicine, Pesticide, Food Technology, Analyis, Flow Injection Analysis, FIA, Scanning Probe Microscopy, Scanning Kelvin Probe Microscopy, SPM, KPM, AFM, SKM, KPFM, SKPM, Nanostructures., Atomic Force Microscopy, KFM
pages
234 pages
publisher
Tryckeriet i E-huset, Lunds universitet
defense location
Hörsal C, Kemicentrum, Getingevägen 60, Lund
defense date
2008-03-13 13:15
ISBN
ISBN 978-91-628-7421-6
language
English
LU publication?
yes
id
e524775b-6571-464b-a871-367dce0c5bf1 (old id 1033528)
date added to LUP
2008-02-18 16:13:55
date last changed
2016-09-19 08:45:15
@misc{e524775b-6571-464b-a871-367dce0c5bf1,
  abstract     = {A new type of Bioelectronic Nanosensor Device with potential applications in medicine,biotechnology and environmental analysis was designed. The nanosensor is based on RISFET (Regional Ion Sensitive Field Effect Transistor) technology. The design of the nanosensor<br/><br>
involves use of a set of nano-sized electrodes on the surface of a silicon chip, giving the chip the ability to sense extremely low concentrations of specific analytes by means of an amplifying process. Analyte ions (or enzymatically generated product ions of these) are<br/><br>
focused by a charged field to become concentrated in a narrow region – a conducting channel – located between two sensing electrodes. The focusing process leads to significant changes in conductivity, increasing the level of the current between the sensing electrodes. The current, registered by a pico-ammeter produced in-house, is a measure of analyte concentration.<br/><br>
<br/><br>
To achieve specificity, the RISFET nanosensor is provided with immobilized enzymes in the form of minicolumns within a flow system. Studies were conducted exploring possibilities of simplifying the system, improving its effectiveness and making it more compact. It appears<br/><br>
that the enzymes should best be moved to an area of the chip in the vicinity of the sensing electrodes, and that branched nanowire structures (nanotrees) be placed on the chip-surface area located between the sensing electrodes to serve as carriers of the enzymes. The nanotrees would ensure an adequate load of enzymes without either the focusing of the ions or the sensing ability being disturbed. Features of this sort are seen as being particularly important for future high-density RISFET nanosensor arrays.<br/><br>
<br/><br>
The basic properties of the sensor were investigated using such analytes as glucose, gluconolactone, acetylcholine and carbofuran. Specificity was found to be achieved when the<br/><br>
enzymes glucose oxidase and acetylcholine esterase were employed. The inhibition of acetylcholine esterase by carbofuran was detectable down to about 20 ng/L. An automatic online biosensor unit for the neurotoxic organocarbamate carbofuran was constructed and was<br/><br>
found to work satisfactorily.<br/><br>
<br/><br>
A number of chip configurations, involving use of different silicon technologies and different electrode arrangements, were designed and characterized. In addition, a study of a Quartz Crystal Microbalance (QCM) biometric sensor was carried out; the sensor surface was functionalized by use of molecularly imprinted nanoparticles specific for (R)- or (S)-propranolol. Frequent use was made in the work as a whole of Atomic Force Microscopy (AFM), Scanning Kelvin Probe Microscopy (SKM) and Scanning Electron Microscopy (SEM). The usefulness of multifunctional nanobiosensor array systems for the surveillance of liquids regarding the presence of many different toxic and biomedically relevant analytes, and in medical, environmental and biotechnological analyses generally is discussed.},
  author       = {Risveden, Klas},
  isbn         = {ISBN 978-91-628-7421-6},
  keyword      = {Regional Ion Sensitive Field Effect Transistor,Region Ion Sensitive Field Effect Transistor,RISFET,Conducting channel,Bioelectronic Nanosensor,Bioelectronic,Biosensor,Nanosensor,Chemical Sensor,Sensor,Semiconductor sensor,Single molecule trapping,Scaling,Protein trapping,Nanoelectronics,Lab-on-a-chip,pico-ammeter,Nanobiosensor,Sample Applicator,Sequential Batch Analysis,Sequential Batch Analysis System,SBAS,Nanowire,Branched nanowire structure,Nanotree,Nanorod,Nano processing,Micro processing,Electron Beam Lithography,EBL,UV-lithography,Molecular Imprinting,DUV-lithography,Moleculary Imprinted Polymers,MIP,Biomimetics,QCM,Biomimetic sensor,Quartz Crystal Microbalance,QCM-D,Nanoparticles,Acetylcholine esterase,Glucose oxidase,Glucose,Gluconolactone,Propranolol,Gluconate,Carbofuran,Neurotoxic,Environmental analysis,Biomedical Analysis,Biotechnology,Medicine,Pesticide,Food Technology,Analyis,Flow Injection Analysis,FIA,Scanning Probe Microscopy,Scanning Kelvin Probe Microscopy,SPM,KPM,AFM,SKM,KPFM,SKPM,Nanostructures.,Atomic Force Microscopy,KFM},
  language     = {eng},
  pages        = {234},
  publisher    = {ARRAY(0x9880fb8)},
  title        = {Bioelectronic Nanosensor Devices for Environmental and Biomedical Analysis},
  year         = {2008},
}