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 TECHNIQUES
MAY BE USEFUL
PHYSICAL
TRANSDUCER
BIOLOGICAL
MOLECULE:
Electronic, e.g. FET
ENZYMES
Electrochemical,
e.g Graphite/Ag-AgCl
electrodes
ANTIBODIES
Optical, e.g. fibre or
planar waveguides
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
Immobilised capture
antibody on the
surface of the fibre
Chemiluminescent
immunoassay
reagents
flow through
Thick (multimode)
optical fibre
Light out to optical
processing
Succesfully
developed at Dstl
Porton Down
but need extensive
support to collect,
concentrate and
measure the
analyte
Detection of air-borne agents at low concentrations
Airborne
threat
Aqueous
Buffer
Air
sampler
Cyclone
Concentrator
Control
circuitry
Best suited to a large vehicle
Assay
Reagents
Biosensor
Array
Display
Sensor
Outputs
Combined Water Filter and Optical Immunosensor
MULTI-ANALYTE TESTING COMMON
TO BOTH AREAS
EXAMPLE, DRUGS OF ABUSE
Acetaminophen
Ethanol
Amphetamine/ Methamphetamine
Methadone
Barbiturates
Opiates
Benzodiazepines
Phencyclidine II
Benzodiazepines-Serum
Propoxyphene
Cannabinoids
Salicylate
Cocaine Metabolite
Tricyclic Antidepressants
CHEMICALLY SENSITIVE FET CHIP:
A technique with potential in multi-gate sensing
ENCAPSULATED
AREA
METAL
CONTACT
PADS
FET (conventional)
50 mm
BARE GATE FETs
BARE GATE:
OVERLAY WITH THIN FILM
CONTAINING ORGANIC OR
BIOMOLECULE, e.g.
IONOPHORE: VALINOMYCIN
ENZYME: PENICILLINASE
Gate compensation voltage
constant Ids
RESPONSE OF A POTASSIUM SENSITIVE FET
Gate membrane - Valinomycin : Dioctyl phthalate : PVC 1:64:35
This success has not been carried through to more relevant analytes
Vg / mV
Gate compensation voltage
constant Ids
RESPONSE OF A PENICILLIN SENSITIVE FET
Gate membrane - Penicillinase entrapped in polyacrylamide
Extension from enzyme-based to antibody based FETs is desirable
Penicillin concentration / M
A standard immunoassay procedure
FLUORESCENT SANDWICH IMMUNOASSAY
UNBOUND LABELLED
ANTIBODY
FLUOROPHORE
BOUND LABELLED
ANTIBODY
ANALYTE
CAPTURE
ANTIBODY
SUBSTRATE (e.g. glass or plastic)
Low concentration detection essential in both areas
10-12
10-10
10-8
10-6
10-4
10-2 Analyte concn
moles / litre
Glucose
Digoxin
Oxytocin
Theophylline
Insulin
Therapeutic drugs
Cortisol
Aldesterone
hCG
Metabolites
Small hormones
Protein hormones
IgM
Antibodies
Rh
Cellular antigens
Influenza (elderly)
Influenza (Paediatric)
Hepatitis
Viral antigens
Tumour antigens
a - foetoprotein
106
108
1010
1012
1014
1016
Analyte molecules
per cm3
Water = 3.3x1022
CAPILLARY FILL FLUORESCENCE IMMUNOSENSOR
(Manufacture based on LCD cell fabrication)
UPPER GLASS FACE
THIN FILM
WAVEGUIDE
LOWER GLASS FACE
BUFFER
LAYER
EQUILIBRIUM RESPONSE CURVE
Sensitivity 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 problem
Microfluidics looks hopeful but yet to deliver
• Multigate devices
Several analytes
High specificity – several epitopes
Lack of a single detector molecule
array processing e.g. neural net
Internal calibration