ethanol methadone opiates phencyclidine ii propoxyphene salicylate tricyclic antidepressants...

BIOELECTRONICS AND SAFETY/SECURITY

Common aim of much biological/medical diagnostic research and security research

• detection of biological organisms and organic molecules • detection of drugs and explosives at ports and airports;• detection of drugs in general;

Other areas of medical research, e.g. epidemiology, may also play a role in wider considerations of chemical and biological

defence strategies.

BIOSENSOR TECHNIQUESMAY BE USEFUL

PHYSICALTRANSDUCER

Electronic, e.g. FET

Electrochemical, e.g Graphite/Ag-AgCl electrodes

Optical, e.g. fibre or planar waveguides

BIOLOGICAL MOLECULE:

ENZYMES

ANTIBODIES

Gives the sensor specificity to complex organic molecules

Most efforts at developing PCR technology have been aimed at the HTS laboratory where parallelism and automation are used to maximise throughput. For point-of-care or field testing, new approaches are required to allow the rapid processing of single or low numbers of discrete samples. Remote testing often requires that the test has to be carried out by unskilled operators and it may not be possible, in the field, to utilise the control measures used routinely within the lab to minimise contamination.

Martin A Lee, Identification Group, Dstl Porton Down

Flow through Evanescent Field Immunosensor

Thick (multimode)optical fibre

Immobilised captureantibody on the

surface of the fibre

Light out to opticalprocessing

Chemiluminescentimmunoassay

reagentsflow through

Succesfully developed at Dstl

Porton Down

but need extensive support to collect, concentrate and

measure the analyte

CycloneConcentrator

Airsampler

AqueousBuffer

AssayReagents

BiosensorArray

DisplaySensorOutputs

Controlcircuitry

Airbornethreat

Detection of air-borne agents at low concentrations

Best suited to a large vehicle

Combined Water Filter and Optical Immunosensor

MULTI-ANALYTE TESTING COMMONTO BOTH AREAS

EXAMPLE, DRUGS OF ABUSE

Acetaminophen

Amphetamine/ Methamphetamine

Barbiturates

Benzodiazepines

Benzodiazepines-Serum

Cannabinoids

Cocaine Metabolite

Ethanol

Methadone

Opiates

Phencyclidine II

Propoxyphene

Salicylate

Tricyclic Antidepressants

CHEMICALLY SENSITIVE FET CHIP:A technique with potential in multi-gate sensing

ENCAPSULATEDAREA

METALCONTACT PADS

BARE GATE:OVERLAY WITH THIN FILMCONTAINING ORGANIC ORBIOMOLECULE, e.g.IONOPHORE: VALINOMYCINENZYME: PENICILLINASE

BARE GATE FETs

FET (conventional)

50 m

RESPONSE OF A POTASSIUM SENSITIVE FETGate membrane - Valinomycin : Dioctyl phthalate : PVC 1:64:35

This success has not been carried through to more relevant analytes

Gat

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Penicillin concentration / M

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RESPONSE OF A PENICILLIN SENSITIVE FETGate membrane - Penicillinase entrapped in polyacrylamide

Extension from enzyme-based to antibody based FETs is desirable

FLUORESCENT SANDWICH IMMUNOASSAY

UNBOUND LABELLED ANTIBODY

BOUND LABELLED ANTIBODY

ANALYTECAPTURE ANTIBODY

SUBSTRATE (e.g. glass or plastic)

FLUOROPHORE

A standard immunoassay procedure

Metabolites

Therapeutic drugs

Small hormones

Protein hormones

Antibodies

Cellular antigens

Viral antigens

Tumour antigens

Analyte concn

moles / litre10-12 10-210-10 10-8 10-410-6

GlucoseTheophyllineDigoxin

Oxytocin Aldesterone Cortisol

Insulin hCGIgM

Rh

Hepatitis

Influenza (elderly) Influenza (Paediatric)

- foetoprotein

106 1016108 1010 10141012Analyte molecules per cm3

Water = 3.3x1022

Low concentration detection essential in both areas

CAPILLARY FILL FLUORESCENCE IMMUNOSENSOR (Manufacture based on LCD cell fabrication)

BUFFERLAYER

UPPER GLASS FACE

THIN FILM WAVEGUIDE

LOWER GLASS FACE

EQUILIBRIUM RESPONSE CURVESensitivity lost on incorporation into CFFD sensor

CAPILLARY FILL FLUORESCENCE IMMUNOSENSOR Internal Standards – important in both remote sensing and

in medical sensing (to meet FDA requirements)

BIOSENSORS AND SAFETY/SECURITY

• Sensitivity - sacrificed - major problemMicrofluidics looks hopeful but yet to deliver

• Multigate devices Several analytes High specificity – several epitopes

Lack of a single detector moleculearray processing e.g. neural net

Internal calibration