Biosensors: a brief tutorial No. 1: what is a biosensor?




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© Medical Device Technology 1994

Biosensors: a brief tutorial

No. 1: what is a biosensor?


Immunosensors and optrodes? Chemical canaries and SQUIDS? Evanescent waves and resonant mirrors? Enzyme electrodes and glucometers? Biochips and biocomputers? Jargon and more jargon used to describe certain types of biosensors and their sensing principles. For the last decade, biosensors have been touted as the means to revolutionise almost all aspects of medical technology- dramatically improving patient care and cutting overall operating costs, while nevertheless providing potentially billion-dollar markets for sensor manufacturers. The medical technologist must be aware of what biosensors are, what they can do and- perhaps as importantly- what they cannot.

In this and forthcoming issues of MDT, I hope to aid the reader to make sense of the "biosensor jungle"- this group of powerful but often overhyped devices. "Biosensor" is a word that is often quoted and often misused. The obvious point of departure is the obvious question- what is a biosensor? This is where the first problem crops up... There are as many definitions around as there are prototype biosensors and each has a different shade of meaning! So for what it is worth, here is my mine!

A biosensor is analytical device incorporating a deliberate and intimate combination of a specific biological element (that creates a recognition event) and a physical element (that transduces the recognition event).

This, not surprisingly, is still somewhat vague, so to gain a better understanding of the above, let us first dissect the word into its two, intimately-combined components; "bio" and "sensor". I shall pay most attention to the former- if biosensors are special, it is mainly due to the "bio".

The bioelement is usually an enzyme or an antibody, both of which merit further presentation. Enzymes are large protein molecules that catalyse chemical reactions. They are synthesised by cells and are used as tools to do the cell's. chemistry. In a simplified scheme, the enzyme participates actively in the transformation of chemical A (the substrate) to chemical B (the product) but remains unchanged at the end of the reaction (Figure 1).


Figure 1


+ gives


<<
which dissociates to give and



In the organism, enzymes are the tools that digest food substances; they synthesise many of the chemicals needed by the organism (including other enzymes); they degrade other proteins that have served their purpose, thus recycling the components; they participate in processes such as the clotting of the blood. All this complex chemical activity means one thing- as tools, enzymes must be extremely specific in their action- any given enzyme will always turn A into B and never C (if you want to make C from A, then there will be another, dedicated enzyme to do it). Equally, the same enzyme will never accept substance D and turn it into B. This specificity relies on the fact that by virtue of their exquisite three-dimensional structure, enzymes can recognise differences of a single atom in the substrate's chemical structure. This makes all the difference in whether the enzyme accepts a reactant or not.

In biosensors, enzymes are again being used as specific tools- because synthetic organic chemistry has not yet come up with anything that does the job as well. This specificity of enzymatic action is the basis for the specificity of enyzme-based biosensors (Figure 2)- if, in a biosensor, you incorporate an enzyme that is specific for reaction with glucose, you have the basis of a sensor for glucose and glucose alone. Your sensor will not detect a substance that is related very closely chemically. The signal should come only from the change in the transducer provoke by the interaction of glucose and the glucose-reactive enzyme (although in practice, non-specific, interfering signals do intervene-but that is another story...).



Figure 2- substance-specific recognition in the general biosensor principle





Onto the second major family of biomolecules used in biosensors- the antibodies. These are also proteins, produced by the immune system of higher animals in response to the entry of "foreign" materials into the body- for example, viruses and bacteria (and implanted medical devices!). In contrast to enzymes, antibodies do not (usually) catalyse chemical transformations but rather undergo a physical transformation- they bind tightly to the foreign material (the antigen) that provoked the response and mark it for attack by other elements of the immune system. Antibodies are also very specific- they need to be, in recognising and binding to the foreign substance only and not to materials native to the organism. This specificity is capitalised upon by biosensor researchers. Typically, antibodies specifically directed against the substance of interest (i.e. the desired analyte) are immobilised on the transducer of biosensor. Then, the sensor is exposed to the intended medium (e.g. blood or other biological fluid). If antigen is present in that medium, it will be bound by the antibody to form a larger, antigen-antibody complex. This will change some physicochemical parameter (usually mass or an optical parameter) of the environment at the transducer surface of the sensor (Figure 3) and that change is subsequently detected.



Figure 3. Schematic action of an antibody-based immunosensor.





So, how about the "other half" of the happy marriage of animal/vegetal and mineral? The sensor element can be just about any means that technology-crazy human-kind has come up with to detect physicochemical change- but here are the parameters most often sensed- in rough order of popularity;

electric current, electric potential, intensity and phase of electromagnetic radiation (usually visible light), mass, electric conductance, electric impedance, temperature, viscosity.

I will not dwell here on the sensor side as again, most of the novelty of biosensors comes from the "bio" side, and MDT readers may also be more familiar with the transducer technology. Most of the transducers have solid theoretical groundings and a long career of practical employment in physisensing.

As a concluding remark- and as a lead-in to the next article- I should like to emphasise that the exquisite specificity produced by 3 billion years of evolution has been harnessed by science to produce biosensors for almost every chemical of (medical) interest. But if biosensors are so great, then why is it taking so long for them to make a serious commercial impact? And which areas in health-care should they be invading? Now we know what biosensors are, we should ask what they can and cannot do in health-care- and how people are trying to turn those actions into products.


© Medical Device Technology 1994
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