Biosensors are analytical
devices which are capable
of providing either
qualitative or quantitative
results.
Clinical relevance
Point of Care (PoC) analysis
becoming increasingly important
primary and secondary care
Biosensor devices - where speed
makes difference in early diagnosis
and Infection
trying to reduce the time between diagnostic
information and when treatment is provided.
particulary in an area where time is of essence e.g in
some disease cases. (allows information to be
available in minutes rather than days)
Enable personalised medicines -
allows for stratified clinical
interventions and improved patient
outcome
reduces waste
How does the natural world
sense things
Drug/ explosive sniffer
dogs better than any
artificial devices
Moth Pheromones Able to detect
ONE MOLECULE!
Human sense of
smell thousands of
smells at ppm
sensors
Integrated device detects its environment and
gives the user a response Sensitivity can be as
high as ppt detection Specificity often high
sometimes broader
physical sensors
heat, light, temperature,
radiation (smoke alarm)
pH, metal ions,
oxygen, toxic gases
these are all examples of
sensors but they are not
biosenseors
ppt= parts per trillion
compoents of a bio sensor
recognition component
All are, or rely
on, proteins
electronics
stability
environment
limitations of molecular recognition
Antibodies – size of target
Antibodies – toxicity in host
Enzyme - finding one suitable
Recognition - Catalytic
binding events
Enzymes
selective binding of analyte, enzyme mediated chemical
reaction, reaction products detected in transduction
system eg. Peroxides from oxidases, NADH from
dehydrogenases, only limited number of suitable enzymes
available, Km of enzyme dictates analytical range, can be
fragile / costly, can use chain of enzymes to achieve
results, immobilization can affect performance
Problem is that there is a limited
number of enzymes.
sensitivity and affinity
km is a function of the sensitivity of the
biosensor it is where you see half the
reaction velocity (1/2 vmax)
glucose sensors
e.g glucose oxidases
enzyme assay: glusose sensors all use the
same sensor. glucose oxidase. it oxidises
glucose down to gluconic acid. this reaction also
produces hyrogen peroxide which can be
detected very easily at the surface of an
electrode, the hdrogen peroxide is reduced and
produces electrons which go into the sensor
and that is what you see.
sense blood glucose levels and
glucose levels in sweat.
Recognition - Affinity
binding events
Antibodies
Binding only – no chemical reaction,
suitable for large molecules, less
useful for small molecules, raised via
animals , wide applicability, high
affinity, can be fragile and costly
sensitivity and affinity
Molecularly Imprinted
Polymers
suitable for large and
small molecules
Moderate affinity
Robust Cheap
possible improvements are increasing
affinity, Imprinting on surfaces, Novel
transduction methods, Computational
Molecular Modelling for design of
Polymer
how its done
(i) pre-polymerisable complex
(ii) polymerisation (iii) template
removal
In principle, the simplest form of
transduction weigh the analyte after binding
onto immobilized affinity receptor sites
in practice, v. tricky and
not a very convenient
sensor Can be very
sensitive to non-specific
changes
What would we need? Property of a
solid that changes due to minute
changes in the mass of that solid
Property that can be monitored very
accurately
Piezoelectric materials
a single crystal of quartz can be made to oscillate
at its resonant frequency Most crystals of current
interest resonate between 5 to 30 MHz
The resonant frequency can be measured
very accurately
When mass changes, resonant frequency of system changes This
change can also be measured very accurately The change is
proportional to the increase in mass Can be used to monitor binding
to an affinity surface
These devices are called: Quartz Crystal
Microbalances (QCMs)
Mass transduction: surface acoustic
waves
The speed a wave travels
across a surface changes
when mass increase
The increase in mass due to an
‘affinity binding event’ can therefore
be monitoring the time taken for wave
to move a set distance
Various modes of wave
propogation are available
Transverse (90deg to plane
of crystal and direction of
travel)
Longitudinal (In plane of crystal
and direction of travel
Shear (In plane of crystal
and 90deg to direction of
travel
Benefits of Biosensors
Fast
Suitable for PoC applications
Needs of an ageing population
Cheap
Instrument cheap, sensor can be v. cheap
often disposable if “one-shot”
Portable
Diagnose wherever it is needed
“hostile” environments OK
Non-skilled operation
No pr little sample prep.
Electronics interpret the signal
Can be robust
"a device that recognizes an analyte in an appropriate sample and
interprets its concentration as an electrical signal via a suitable
combination of a biological recognition system and an
electrochemical transducer.”
biorecognition is the part of the sensor
that interacts with the environment. it
reacts/ bind/ targets or reacts with one
specific molecule within a mixture of a lot
of molecules.