Biosensing and nucleic acid analyses – Quantum Instruments Sensor User Manual

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Sensors & Transducers Journal, Vol.76, Issue 2, February 2007, pp.935-936

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Fig. 2. This "medical telesensor" chip on a fingertip can measure and transmit body temperature

(Courtesy: Oak Ridge National Laboratory, ref. 32).


3. Biosensing and Nucleic Acid Analyses


Over the past two decades, the practice of DNA sequence detection has become more ubiquitous and
will continue to increase exponentially in genetics (primary patient diagnosis, carrier detection and
prenatal diagnosis), pathology, criminology, food safety and biological warfare agents. This has been
driven partly by the quantity of DNA sequence information that we have collected on humans and
other organisms and partly by the increasing technological advances that provides us with the tools
needed to develop new techniques to monitor biorecognition and interaction events. Current
methods[33] for the identification of a particular DNA base sequence in a biological sample begin with
the isolation of intact, double-stranded DNA and employ the polymerase chain reaction (PCR) to
amplify the region of interest. The PCR product can then be subjected to electrophoresis or adsorbed
directly onto a membrane, which is then exposed to a solution containing a DNA probe which has been
chemically or enzymatically labeled with a radioactive material, chemiluminophore or hapten / ligand
such as biotin to provide detectable signal for DNA hybridization. Radioactive materials are extremely
sensitive, but have the obvious disadvantage of short self-life & high cost. Radioactive assay can not
be done in open or ordinary labs which are not well equipped for handling, storage & dumping of
radioactive materials. Fluorescent dye labels are expensive, they photobleach rapidly & are less
sensitive. Most recently, Luminescent semiconductor nanocrystals (or “quantum dots”, QD) have been
used as labels for bioanalytical applications [34-35]. Thermoquenching and extremely high cost are
potent disadvantages of Quantum dots and hence generally limited to use in sensitive research
experiments. There fore, large-scale, routine clinical screening based on gene diagnostics is limited by
the current available technologies. Remarkably, DNA Biosensor technology can provide rapid, simple
and low-cost on field detection of specific DNA sequence (pathogenic, virulent, transgenic) or point
mutations that are responsible for, or linked to, inherited diseases. Diseases such as cystic fibrosis,
muscular dystrophy, sickle-cell anemia, phenylketonuria,

β-thalassemia and hemophilia A are known

to be associated with specific changes in normal DNA base sequence. The list of known genetic
abnormalities that cause, or are associated with, disease states will continue to expand as the
sequencing of the human genome continues. During sensing of nucleic acids, single-stranded (ss)
oligonucleotide probe are immobilized onto transducer surface forming a recognition layer that binds
its complementary (target) DNA sequence to form a hybrid. The hybridization reaction is recognized
and analytical signal (light, current, frequency) is passed by the transducer to the processor to provide
a readable output. The measurement system (transducer and read out device or signal processor) can be
gravimetric [36], electrochemical [37], optical [38], electrical [39], surface plasma resonance [40]
based. Electrochemical DNA biosensor based detection show superior results over the other existing
measurement systems. Basic principle of DNA biosensor is based on the properties that 1) DNA is
double helical and has strong stacking interaction between bases along axis of double-helix and the
base-pairing interactions between complimentary sequences are both specific and robust. 2) Double

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