Quantum Instruments Stud Sensor Sensor User Guide

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Sensors & Transducers Journal (ISSN 1726-5479) is a peer review international journal published monthly online by International Frequency Sensor Association (IFSA).  
Available in electronic and CD-ROM. Copyright © 2007 by International Frequency Sensor Association. All rights reserved.  
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Sensors & Transducers Journal  
Contents  
Volume 76  
Issue 2  
ISSN 1726-5479  
February 2007  
Research Articles  
Biosensors: Future Analytical Tools  
Vikas, Anjum, C. S. Pundir…………………………………………………………………………………...  
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945  
Advances in Biosensing Methods  
Reema Taneja, Kennon C. Shelton, Raymond Carlisle, Ajit Sadana …………………………………..  
Interface Layering Phenomena in Capacitance Detection of DNA with Biochips  
Sandro Carrara, Frank K. Gürkaynak, Carlotta Guiducci, Claudio Stagni, Luca Benini, Yusuf  
Leblebici, Bruno Samorì, Giovanni De Micheli…………………………………………………………….  
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978  
A Simple and Sensitive Flow Injection Optical Fibre Biosensor Based on Immobilised  
Enzyme for Monitoring of Pesticides  
B. Kuswandi, N. W. Suwandari ……………………………………………………………………………..  
Design and Characterization of a Solid-State Piezoelectric Transducer Chemical Sensor for  
Chromium Ions Contamination in Water  
Selemani Seif………………………………………………………………………………………………….  
991  
Influence of Liquid Petroleum Gas on the Electrical Parameters of the WO3 Thick Film  
R. S. Khadayate, J.V. Sali and P. P. Patil……………………………………………………………........  
1001  
Synthesis, Characterization and Acetone Sensing Properties of Novel Strontium(II)-added  
ZnAl2O4 Composites  
J. Judith Vijaya, L. John Kennedy, G. Sekaran, K.S. Nagaraja …………………………………………  
1008  
1018  
Short Communication  
Investigating Solids, Liquids and Gases by Surface Photo-Charge Effect (SPCE)  
Ognyan Ivanov…………………………………………………………………………………………………………….  
Authors are encouraged to submit article in MS Word (doc) and Acrobat (pdf) formats by e-mail: [email protected]  
International Frequency Sensor Association (IFSA).  
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Sensors & Transducers Journal, Vol.76, Issue 2, February 2007, pp.935-936  
Sensors & Transducers  
ISSN 1726-5479  
© 2007 by IFSA  
Biosensors: Future Analytical Tools  
Vikas, Anjum and C S Pundir*  
Department of Biochemistry & Genetics, Maharashi Dayanand University, Rohtak-124001, India  
Tel.: 00 91 09215570591; e-mail: [email protected]  
Received: 10 October 2006 / Accepted: 22 February 2007 / Published: 26 February 2007  
Abstract: Biosensors offer considerable promises for attaining the analytic information in a faster,  
simpler and cheaper manner compared to conventional assays. Biosensing approach is rapidly  
advancing and applications ranging from metabolite, biological/ chemical warfare agent, food  
pathogens and adulterant detection to genetic screening and programmed drug delivery have been  
demonstrated. Innovative efforts, coupling micromachining and nanofabrication may lead to even more  
powerful devices that would accelerate the realization of large-scale and routine screening. With  
gradual increase in commercialization a wide range of new biosensors are thus expected to reach the  
market in the coming years.  
Keywords: Electrode, transducers, genetic screening, food analysis, bioterrorism, environment  
monitoring  
1. Introduction  
Modern economy is technology driven, promising revenues that are mind-boggling. Biosensor is one  
such product of biotechnology that is becoming increasingly popular in fields like environmental  
monitoring [1-2], bioterrorism [2-3], food analyses [4] and most importantly in the area of health care  
and diagnostics [5]. This rapidly expanding field has an annual growth rate of 60 %, with major  
impetus from the health-care industry (30% of the world’s total analytical market) supported with  
other analytical areas of food & environmental monitoring including defense needs [6]. There is  
clearly a vast market exponential potential as less than .1% of this market is currently using biosensors.  
Research & Development in this field is wide and at the forefront of multidisciplinary science that  
involves the collaboration of physics, chemistry, biology, nanotechnology, electronics and software  
engineering. The concept of biosensors is just four decades old and the feasibility of biosensing was  
first demonstrated by an American scientist Leland C. Clark in 1962. He described how to make  
electrochemical sensors more intelligent by adding "enzyme transducers as membrane enclosed  
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Sensors & Transducers Journal, Vol.76, Issue 2, February 2007, pp.935-936  
sandwiches”[7]. This idea was commercially exploited in 1975 with the successful launch of the  
Yellow Springs Instrument Company’s glucose analyzer based on the amperometric detection of  
hydrogen peroxide (H2O2). Since then, many biosensors have been developed to detect a wide range of  
biochemical parameters, using a number of approaches, each having a different degree of complexity  
and efficiency. Recently, the most fascinating and prospective sensors includes Immunosensors [8-9]  
and Nucleic acid sensors [10-11], based on affinity reactions between Ab-Ag & hybridization reaction  
of complimentary ssDNA oligonucleotides respectively.  
In general, a biosensor is an analytical device, which detects, transmit and record the information  
regarding the physiological, biochemical change or the presence of a specific analyte (a chemical or  
biological substance that needs to be measured) by producing a signal proportional to the concentration  
of the target analyte. A basic biosensors assembly includes a receptor, transducer and processor  
(amplification and display) as shown in Figure 1.  
Fig. 1. Schematic diagram showing the main components of a biosensor. The biocatalyst (a) converts the  
substrate to product. This reaction is determined by the transducer (b) which converts it to a signal. The output  
from the transducer is amplified (c), processed (d) and displayed (e).  
(Reproduced with permission from ref. 6).  
Technically, it is a probe which incorporates a biological/ biologically derived sensing element (e.g.  
whole cells/ antibodies/ enzymes/ nucleic acids) forming a recognition layer, that is either integrated  
within or intimately associated to the second major component of biosensors that is a transducer via  
immobilization, adsorption, cross-linking and covalent bonding so that the close proximity of the  
biological component to the transducer is achieved. This is necessary so that the transducer can rapidly  
and easily generate the specific signals in response to the undergoing biochemical interactions,  
secondly the transmittance should be proportional to the reaction rate of biocatalyst with the measured  
analyte for a high range of linearity. The transducer critically acts like a translator, recognizes the  
biological/chemical event from the biological component and transforms it into another signal for  
interpretation by the processor that converts it in to a readable/ measurable out put. The transducer can  
take many forms depending upon the type of parameters being measured. They may be a)  
Amperometric: detect changes in current at constant potential [12], b) Potentiometer: detect changes in  
potential at constant current [13], c) Piezoelectric: detect the changes in mass [14], d) Thermal:  
measures changes in temperature [15], e) Optical: detects change in light transmission [16].  
Since, these devices offer an excellent combination of the selective biology with the processing power  
of nano-electronics to generate rapid, simple and sensitive signal proportional to the target analyte;  
they are regarded as potent substitutes to conventional analytical techniques. These low complexity  
devices are suited for use at the point of care by healthcare workers with minimal training. By  
eliminating a number of steps and much labor, the instrumentation may save a lot of money & time for  
laboratories and hospitals. It would therefore in the near future be possible to measure group of  
biochemical parameters simultaneously from a single finger prick blood sample. Besides, they allow  
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Sensors & Transducers Journal, Vol.76, Issue 2, February 2007, pp.935-936  
the clinical analysis to be performed at the bedside, in the critical care units and doctor’s clinic rather  
than in the centralized laboratories.  
2. Biosensors in Health Care and Diagnostics  
With rising healthcare costs and to improve patient care, diagnostic laboratories have been challenged  
to develop new tests that are reliable, cost–effective and accurate and to optimize existing protocols by  
making them faster and more economical. Although there are number of commercial successes, but  
most successful to date is the glucose biosensor [17] for routine monitoring of glucose in blood by  
individuals suffering from diabetes. The basic principle is that glucose is recognized by the bioreceptor  
layer i.e. the glucose oxidase enzyme to yield the redox active species like hydrogen peroxide (H2O2)  
and gluconic acid. Out of these H2O2 passes through a series of membranes and is finally detected at  
the working electrode. The resulting electrical current is amplified and recorded. Other compounds,  
which may give an artificial signal or foul the electrode, are excluded by the membrane system.  
Companies are fabricating implantable biosensors that can trace blood glucose levels and  
simultaneously deliver insulin. For example “Microchips” is testing a chip implant that offers long  
term, time-controlled drug delivery [18]. Compatibility with microfabrication and ability to store and  
release drugs on demand would have potential applications in medical diagnostics, industrial process  
monitoring and control, combinatorial chemistry, microbiology, and fragrance delivery[19]. More  
importantly, it may provide new treatment options to clinicians in their fight against disease. The next  
step is to develop a manually, wirelessly controlled biosensor that detects and treats an acute condition,  
and then a biosensor that will approximate an artificial organ. This will permit sensing a condition and  
responding automatically without user intervention.  
Biosensors also offer enormous potential in detecting wide range of analytes that are regularly needed  
to show a patient’s metabolic state especially for those who are hospitalized, more so if they are in  
intensive care. Critical care is one of the most challenging (and stressful) areas of medicine, in the  
sense that the decision makers (primarily doctors, nurses and ambulance staff) must take their  
decisions quickly. At the moment of first examination, the patient’s clinical state is usually unknown,  
and once known, it is prone to rapid change. The earlier these fundamental clinical data are provided; a  
reasoned therapeutic decision can be taken instantly for enhancing success rate. Biosensors that  
facilitate the measurement of calcium[20], lithium[21], lactate[22], cholesterol[23], urea[24], uric  
acid[25], oxalate[26], triglycerides[27], ascorbic acid[28] and creatinine[29] have been demonstrated  
and needs refinement for commercial viability. External biosensors are used in emergency rooms as  
point-of-care diagnostic units – such as I-Stat’s “lab on a chip”, which can reveal almost immediately  
whether a patient is under cardiac arrest by testing blood chemistry[30]. Similarly, it will be extremely  
helpful to have instantaneous on-site determinations for creatinine, sodium, potassium, chloride, and  
CO2 levels of patients in the dialysis unit of a hospital or at a hemodialysis center.  
Several variants of the classical biosensors are already thriving in the medical field. A new biosensor  
technology based on magneto-resistive sensors is introduced by Philips [31]. This biosensor measures  
the magnetic field created by magnetic nano-particles that bind to target molecules in a biological  
assay. Compared with optical sensing methods, the use of magnetic nano-particles eliminates the  
additional steps required to bind optical labels to the target molecules and improves sensitivity.  
Oak Ridge National laboratory (ORNL) has developed “Medical Telesensor” chip (Fig-2) which can  
measure and transmit data related to body temperature [32]. Similar chips are being developed as a  
defense need for military personals to transmit data essential data to the remote monitor. This monitor  
alerts the medical team in critical circumstances.  
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Sensors & Transducers Journal, Vol.76, Issue 2, February 2007, pp.935-936  
.
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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Sensors & Transducers Journal, Vol.76, Issue 2, February 2007, pp.935-936  
stranded DNA shows long- range electron transfer through π stacks of aromatic rings of base pairs [41-  
42]. The first example of a DNA chip, called the eSensorTM, was produced by Motorola Life Sciences  
Inc. [43]. eSensorTM bioelectric chips also successfully detected 86% of the HPV types contained in  
clinical samples[44]. Toshiba’s electrochemical DNA hybridization detection system is called the  
GenelyzerTM [45]. It contains an electrochemical DNA chip that is able to analyze and type single-  
nucleotide polymorphisms (SNPs) and common DNA sequence variations by using the redox-active  
dye Hoechst33258 [46].  
4. Applications in Food Analyses and Quality Assurance  
Safety monitoring and quality control of foods are essential for food industry and the use of biosensors  
allows the assessment of food safety in real time. Hence biosensors have been developed for  
automated process control and provide a good alternative to other methods which are tedious, time &  
energy consuming and may require expensive instruments and reagents in addition to considerable  
technical skills4. The importance of on-line measurement compared to a laboratory measurement in  
terms of process control is firstly its response time. Sampling and subsequent analysis in a laboratory  
involves a time delay which can be sometimes several days. Although laboratory instruments have  
some inherent advantages, on-line biosensor describes the real time state of the process. Data  
generated from the biosensor provide rapid and/or continuous feedback information which can help the  
food processor both reduce wastage and increase productivity by incorporating microbiological and  
quality control into processing line. Because foods are highly unstable materials and can quickly  
undergo rapid and often detrimental changes, process control is an uncertain and doubtful strategy.  
Because of this, food industry needs instruments which will simultaneously monitor the parameters of  
production lines and report data to the computer for feedback control.  
Most of the electrodes used in biosensors are often based on the measurement of O2 consumption  
because there are at least 50 known oxidases acting on fatty acids, hydroxy acids, sugars, amino acids,  
aldehydes, etc. Using this concept ethanol, methanol, lactose, lactic and acetic acid, glucose and  
galactose on line biosensors have been developed by different researchers.  
Beer, wine, bread and dairy industry suffer from lack of monitoring the growth conditions of  
microorganisms which must be kept at certain limits. On-line biosensors offer these industries  
feedback control of both the component and microbial levels of these and similar processes by  
continual on-line monitoring.  
A unique situation that recently has come to light in India is the adulteration of milk with materials that  
are toxic or production of synthetic milk using ingredients such as urea. Biosensors have already been  
developed to check this menace. For example, urea is detected in milk samples by employing the  
enzyme unease. Urea and water are converted to ammonium and bicarbonate ions in the aqueous  
medium. Bicarbonate ions are weak ions so contribute less to the pH change but the alkaline ions due  
to their high alkaline nature contributes maximally to the pH change which is detected by the  
potentiometric transducer.  
5. Biosensors for Environmental Monitoring  
With several countries on the path to acquiring chemical and biological weapons there is now a need to  
develop biosensors for the early detection of these agents in accidental release during production and  
deliberate use by terrorists. Defense applications have become very prominent, particularly since the  
atrocities of September 11th 2002 and the subsequent anthrax attacks. To circumvent this latest threat  
to human health, efforts are underway to develop biosensors that could be used under these situations.  
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Biological and chemical warfare agents have broad threat spectrum, ranging from relatively simple  
chemical agents to complex bioengineered microorganisms. Traditional chemical agents (nerve,  
vesicant, and blood agents) have acute toxicities in the range of 10–3 g/person and are relatively easy to  
detect. Emerging chemical agents (toxic chemicals and aerosols) and bioregulators (neuropeptides and  
psychoactive compounds) are more varied in their chemical structure, requiring more sophisticated  
analytical methods for identification and detection. The most difficult chemical agents to detect are the  
cytotoxins and neurotoxins with chronic toxicities as low as 10–10 g/person. To identify and detect this  
complex array of chemicals, the ideal instrument would respond within min, cover the 15 to 200,000  
dalton threat beside field portability. Despite the public’s anticipation that biosensors with real-time  
detection will be able to monitor biological and chemical weapons, the technology hasn’t caught up  
with expectations. Presently, biosensors in environmental monitoring stations, worldwide can detect  
compounds like anthrax – but detection can take 12 to 24 hours. Sandia National Laboratories, USA is  
developing the µChemLab, a system that detects biotoxins in 5 minutes [2]. Currently they are trying  
to upgrade the µChemLab to integrate both gas-based and liquid-based analysis into one handheld  
device. This type of biosensor could be incorporated into military uniforms and eventually into high  
security buildings.  
6. Future Prospects and Popularization of Biosensors  
Simplicity, quick results and economic advantages are enabling new procedures in hospitals while  
increasing the possibilities for self-care. For the biosensor to be of optimal use, it must be at least as  
precise and standardized as other available technology. Personnel with minimum training should be  
able to use these devices. Collecting and analyzing specimen at the bedside or in the clinic will  
enhance the superior turnaround time of biosensors. Reducing blood specimen volumes to micro (µ)  
level may permit continuous on-line monitoring of critical blood chemistries and has the advantage of  
creating less blood to clean up hence reducing the potential for infectious contamination from patient  
blood. It is anticipated that the health care worker at the bedside of a hospital patient µl aliquot of  
whole blood directly into the chip, and insert the chip into a portable biosensor instrument. In addition,  
a single chip insert may measure multiple parameters. This multi-specialty in itself will save  
considerable time and effort over the specimen processing that constitutes a substantial part of today’s  
laboratory workload. In addition, mass-produced disposable biosensors will make medical diagnosis  
cheaper. The world total analytical market is approx 12000, 000, 000/ year and less than .1% of this  
market is currently using biosensors. Despite huge market potential & except for few commercial  
successes, many of the prototypes of biosensors in our laboratories are not commercially viable. The  
gap between research and the market place still remains wide and commercialization of biosensor  
technology has continued to lag behind the research by several years. Some of the many reasons  
includes: cost considerations, stability and sensitivity issues, quality assurance and competitive  
technologies. Until all these issues are addressed it would be difficult to move these devices from the  
research lab to market place. Biosensors undisputedly have got tremendous applications in healthcare,  
but the level of sophistication, reliability, awareness, cost, availability and marketing of these devices  
are important for deciding whether biosensors will be popular in the near future.  
7. Conclusion  
Biosensors are analytical devices which can transform biological recognition into a measurable signal.  
Our fascination with biosensor world is due to its exponential potential in analytical market. This  
multidisciplinary field offers potential applications in clinical diagnostics, defense, food and beverage  
industry, pollution control. In addition to sensitivity, simplicity and fast processing power, micro  
fabrication technology enhances biosensors with desired specifications. There is a great need to bring  
synergy among R&D institutions and Government, Industrial houses that leads to smooth transmission  
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Sensors & Transducers Journal, Vol.76, Issue 2, February 2007, pp.935-936  
of technology. The level of sophistication, awareness, cost, reliability, availability and marketing are  
all factors involved in deciding, whether biosensors would become popular in near future.  
Acknowledgment  
Biosensor work in author’s lab is funded by Department of Biotechnology and Department of Science  
& Technology, New Delhi.  
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