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    BIOSENSORS

 


tools for detecting biomolecules
 

Introduction

In everyday experience those who wear corrective eyeglasses will be aware that reflections at glass/air
interfaces can be annoying. For many years this level of annoyance has been diminished by the
development of lens coatings which act as 1/4 wave rectifiers.  Deliberate modifications of glass/air or
lasing medium/air interfaces could have very significant impacts on internal reflections at such interfaces
and subsequent dispersion of light. Dispersion losses are undesirable in lasers and optic fibres because
they diminish transmission and/or lasing. Such diminution could be measured. In optic fibres the results
would be light losses. In lasers the results would be significant or total losses in coherent light output. It is
suggested that measurement of such losses could afford very rapid detection of biological agents which
increase dispersion by binding to an agent-specific coating on the medium/air interface.

Lasers

The basic plan for a laser has been unchanged since its first demonstration. A lasing medium, gas, liquid,
or solid is excited by some form of incident energy. A laser, by definition, emits light. Light is trapped inside
the lasing medium by reflection at mirror surfaces (or by total internal reflection). If one mirror surface is
partially transparent, light escapes as a coherent series of wavefronts - laser light.

Appropriate coatings on the emitting face could serve to block or modulate coherent light output. Most
commercial microlasers are based upon transparent semiconductor materials which react to electrical
excitation by emitting photons of a defined wavelength corresponding to the energy potential of the hole
structure. Typical commercial semiconductor lasers are red, although green lasers are also available. Blue
lasers should be commercially available soon and have been demonstrated in the laboratory.

By coating the emitting surface with a suitable receptor structure it should be possible to make microlasers
which are sensitive to specific agents which bind to the receptor.

Already, the technology for specifically binding receptor molecules and a variety of other agents to glass,
metal and plastic surfaces has been well demonstrated.

By tailoring suitable carriers for receptor molecules and their binding agents, it should prove quite
straightforward to engineer an interaction layer which addresses the issue of light output/dispersion/
rectification. This should be an incredibly sensitive detector. Before switching off there may well be an
abrupt drop in coherent light emission, possibly associated with very minor changes in frequency. Such
changes might easily be detected by looking for the "beat" frequency. However, quite simply the extinction
itself should be the most obvious and sensitive probe.

It is of course conceivable that a 2 dimensional array of such probes, each unit or group of units treated for
a specific agent could constitute an easily usable monitor for multiple challenges of both epidemiological or
other interest. Groups of units could provide internal control and protection against false positives/negatives.
By incorporating suitable photodetector technologies these switchable lasers could become core components
of very sensitive detection tools.

Such tools would be extremely robust. With an appropriate power supply and telecommunications unit they
could simply be dropped - or conceivably fired - into an area of interest. Deployment in suitable arrays would
be straightforward and small size and simple engineering would make these cheap throw-away devices.

The major drawback of these detectors is that where the particle density in air is low, there is statistically
little chance of a suitable number of particles interacting with the small surface area constituted by the
substrate surface. This drawback can be offset by assuring that a large volume of sampled air passes over
the surface.

The very major advantage of the successful development of the system described is the capability of exploiting
real time detection and identification of biological agents of disease including living organisms, viruses and toxins.
 

Fibre optics

The same coating technology approach could be applied to a fibre optic detection system. I believe that this also
has certain attractions. Glass fibres, kilometres in length are used for fibre optic transmission. Such fibres are
highly flexible and incredibly transparent. They are usually confined within a cable for data transmission
purposes.

Dispersion losses arise because of microscopic inhomogeneities in the fibre surface or because of short range
variations in refractive index of the glass. In reality the fibres are very fine, much less than hair thickness, and
very flexible. They can be crushed, without breaking, almost like fishing line. Everyone is familiar with glass
wool, which resembles cotton wool balls. A fibre optic glass wool, like aerogel, is very light with a huge surface
area. By treating the glass surface, an enormous surface area for interacting with biological agents becomes
available.  When connected to a laser light emitter at one end and a photon counter at the other extremely
sensitive detection levels can be established.

By having several fibres, emitters and several corresponding detectors, a number of different agents could be
screened, as with a the laser microarray system.

In confidence some specific thoughts on these possibilities can be exchanged with
Karl Simpson.  Details on all the above ideas can be
obtained directly from Bénézech - Simpson.

We are delighted to develop our ideas in partnership with those having an
established presence in the markets of relevance.