Microdevices as Nanolevel Biosensors

Innovative enhanced tools for genetic analysis for biomedical and industrial needs are still under development. One development currently being studied is the eSensor™ DNA Detection System by Motorola Inc., by which reliable DNA testing can be achieved. The living being uses DNA to store its genetic code that describes everything about the organism. Specific fractions of the human DNA reveal valuable data. These data can be utilised for health care and medication. Some of the biosensor applications include:

• Forensics and genetic screening

• Stress response analysis

• Antibody gene expression in transgenic cells

• Identification of patients with high tumor risk

• Biowarfare agents

• Drug discovery

The development of DNA sensors (a DNA sensor is a biosensor) is considered to be the most innovative molecular biology technology due to the fact that these micro or nano systems allow for an easy, accurate, fast and reliable way to analyse many DNA samples simultaneously. The basic element of the DNA sensor is the DNA probe(s). The technology is based on the recognition of oligonucleotides (An oligonucleotide corresponds to a single very short DNA strand) by their complementary genomic sequences (The relative order of base pairs, whether in a DNA fragment, gene, chromosome, or an entire genome). The process of recognition is called hybridisation (Fig.1.2(a)). Hybridisation can be achieved by the optical method, the surface stress method or by electrical detection. The optical method is a traditional method in which the color of the solution changes. The surface stress based hybridization process uses a probe of micro cantilever structures, coated with a detector film that reacts with the specific biomolecules being tested. A biochemical reaction on the cantilever surface changes in the surface stress. The surface stress causes a bending of the cantilever. A piezoresistor integrated with the cantilever reflects the bending variable, and hence detects the presence of DNA. The stress-based detection method is ideal where limited sample preparation is expected as the electrical characteristic based process uses microelectrodes. In this case, the DNA probe is attached to electrodes. There are two opposite electrodes and the electrical resistance between the electrodes is infinite. Similar to the cantilever based method, each probe must be prepared beforehand, i.e., the DNA has to be coated with the probe. The probe has a specific molecular sequence. The active element made from pairs of gold electrodes is sometimes placed in a circular compartment onto which a DNA strand with known sequences is attached. A solution of unknown sequence (target) DNA strands is then brought. Compatible DNA strands bind to the attached probes and the unreacted strands do not. Any DNA that hybridises with the probe is the DNA to be detected. Upon hybridisation, a bridge-like structure is formed on the electrodes. The formation of the bridge the causes electrical resistance between the electrodes to form, which then drops the resistance from infinite to few thousand ohms. This change in resistance is the measure of the presence of DNA. Appropriate instrumentation can be integrated to observe the effect. Such a type of detection method is called a single molecule based detection scheme and is very useful for the detection of specific DNA molecules. Fig.1.2(b) shows how a typical bridge has been formed by the use of an electrical characteristic based hybridisation process. The electrical characteristic based detection of a specific single DNA molecule fragment is very efficient as compared to the surface stress based method. Note that the sensor is a microstructure, but the hybridization phenomenon is at the nanoscale level.

Fig. 1.2. DNA hybridisation (Source: Fuller, Rochester institute of Technology)

Fig. 1.2. DNA hybridisation (Source: Fuller, Rochester institute of Technology)

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Brain Blaster

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