**5. Insights into the future**

The first insight that is important to consider must be whether there are or not advantag‐ es in developing such a variety of biosensors prior to conventional detection systems. The most important advantage that one can think of refers to quick and in vivo early detec‐ tion of severe conditions, which will lead to mature diagnostics at the earlier stages of diseases that today are challenging.With that and searching for utilizing all information on materials and techniques earned from scientific issues of other natures, such as utiliz‐ ing the supramolecular chemistry to design new materials and coupled methods of detec‐ tion that confer richer and reliable information, biosensor development contributed to the development of a number of research fields with some common interests. For example, more accurate information on microfluidic electronics to build sensors; new organic, hy‐ brid and inorganic materials with interesting physical, chemical and morphological prop‐ erties needed to be proposed; better methods to prepare homogeneous and thin films; new supports and electrodes are constantly demanded; new techniques for characteriza‐ tion and properties evaluation, which ask for improvements and new approaches to ex‐ ploit all features of biosensors; new methods of modification and immobilization of biological elements, to cite some of these contributions.

Now, even greater perspectives are lying in the biosensor´s development into the nano‐ technology approach. It had been demonstrated that the use of nanobiosensors can pro‐ vide several advantages not yet considered for conventional systems. They can be built under the nanoscale limit, they need to use similar materials to those used in the large scale devices, but in much smaller sizes. We know for sure that nanoscaled materials pro‐ vide quite distinct properties, which could generate distinct biosensors, maybe even more sensitive and selective biosensors. For example, metallic nanoparticles have their bandgap energies widen at nanoscale, which turns to be a very important optical effect, since it generates a quantum confinement expressed by the observed spectral blue-shifts; magnet‐ ic materials show super magnetic behavior at nanoscale [72, 73, 74] other semiconducting nanoparticles present tunneling and Coulomb blockade effects [62]and all these impres‐ sive properties are not observed for the same thick materials. Some properties are clearly added to the biosensors processed at nanoscale, along with some thought advantages. The first ones that come directly to our minds are the possibility of using a reduced amount of materials in the device construction; reduced power is needed to make biosensors to work and, with it, they can be thought as portable, once they do not require a power source ratter then a small battery; they can be more stable with time; easier to recycle or dispose and, of course, since in nanoscale, we are leading with some new properties, it is expected that the nanobiosensors produced might posses new properties and so, new ca‐ pabilities. With respect to detection and operation of these devices, detection processes thought to be simpler and faster, in constructions that tend to be more friendly, since it do not need bulky detection systems, conferring also the direct advantage of low cost of construction.

showed by Guiseppi-Elie, [70] when polymers such as polypyrrole and polyaniline are combined to hydrogels, they generate bioactive polymers that act as bioreceptor hosting

**•** Aging research: optical biosensors based in fluorescence and bioluminescence emissions are proposed as devices for monitoring certain hormones dosage in the living body, as well as the release and the action of drugs administrated via dietary paths in these hormone levels. [71] The proposal is that an implantable biosensor could, in periods of days or even in the lifespan of an individual, inform about hormone fluctuations and valuable insights into the mode of action of the intervention could result from this monitoring. It is well known that in dietary restriction and other interventions, hormones such as insulin show profound changes. To be able to continuously monitor blood levels of these hormones, drugs or other factors by less invasive methods, could allow, for example, the adjustment of the hormone

The first insight that is important to consider must be whether there are or not advantag‐ es in developing such a variety of biosensors prior to conventional detection systems. The most important advantage that one can think of refers to quick and in vivo early detec‐ tion of severe conditions, which will lead to mature diagnostics at the earlier stages of diseases that today are challenging.With that and searching for utilizing all information on materials and techniques earned from scientific issues of other natures, such as utiliz‐ ing the supramolecular chemistry to design new materials and coupled methods of detec‐ tion that confer richer and reliable information, biosensor development contributed to the development of a number of research fields with some common interests. For example, more accurate information on microfluidic electronics to build sensors; new organic, hy‐ brid and inorganic materials with interesting physical, chemical and morphological prop‐ erties needed to be proposed; better methods to prepare homogeneous and thin films; new supports and electrodes are constantly demanded; new techniques for characteriza‐ tion and properties evaluation, which ask for improvements and new approaches to ex‐ ploit all features of biosensors; new methods of modification and immobilization of

Now, even greater perspectives are lying in the biosensor´s development into the nano‐ technology approach. It had been demonstrated that the use of nanobiosensors can pro‐ vide several advantages not yet considered for conventional systems. They can be built under the nanoscale limit, they need to use similar materials to those used in the large scale devices, but in much smaller sizes. We know for sure that nanoscaled materials pro‐ vide quite distinct properties, which could generate distinct biosensors, maybe even more sensitive and selective biosensors. For example, metallic nanoparticles have their bandgap energies widen at nanoscale, which turns to be a very important optical effect, since it generates a quantum confinement expressed by the observed spectral blue-shifts; magnet‐ ic materials show super magnetic behavior at nanoscale [72, 73, 74] other semiconducting

membranes of enzyme-based implantable biosensors.

levels, retarding aging processes and preventing aging diseases.

biological elements, to cite some of these contributions.

**5. Insights into the future**

132 State of the Art in Biosensors - General Aspects

Nanobiosensors are thought to be as simple as possible, so, in the most recent proposed devices, the more acceptable approach is the label-free nanobiosensor. In this way, in a bi‐ osensor, the recognition element does not need to interact with other molecules or labels. There is no need to target the analyte or activate the biosensor by processes as conjuga‐ tion with an enzyme, resonant energy transfer to generate the desired fluorescence, or chemical processes generated by the incorporation of molecules in order to functionalize the recognition element to produce a luminescent response, and others. In these biosen‐ sors, the probe and target-binding or substrate reactions are expected to be recorded by the transducer in the absence of any labelrequirement. Nevertheless, applications of such nanodimensioned devices are of a great variety, it is evident that the major target is the diagnostic and medical ones. Since these biosensors consist of a nanoscale detection meth‐ od, they can sense target molecules in very low concentration into the body, which con‐ sist of a key factor in early detection of diseases such as breast cancer and AIDS. In fact, this is the idea behind the home method to detect AIDS, the OraQuick® HIV test present‐ ed by Orasure Technologies Inc. Their portable sensor comprises a visually read, qualita‐ tive flow immunoassay for the detection of antibodies to HIV-1 and HIV-2. In the device, HIV-1 and HIV-2 antigens are immobilized on a nitrocellulose strip and reactive antibod‐ ies are visualized by colloidal gold labeled with protein-A. The oral fluid are collected di‐ rectly on the device and the positive test appears within 20 minutes as a purple line at the visor.[75]

Nevertheless, a point that needs to be made is, clearly miniaturization is the focus of many research that have been conducted in this theme, but it also can bring about some undesired properties, which need to be taken into account when engineering a biosensor. It means that not everything in nanoscale is adequate. One must have in mind which problem needs an answer, otherwise there is no scientific method, only the old fashioned "accidental discovery".

## **Author details**

Tatiana Duque Martins, Antonio Carlos Chaves Ribeiro, Henrique Santiago de Camargo, Paulo Alves da Costa Filho, Hannah Paula Mesquita Cavalcante and Diogo Lopes Dias

Chemistry Institute, Campus II, Federal University of Goias, Goiania, Brazil
