Biosensors mass sensitive sensors

Earlier, the electrochemical detections were mostly employed in chemical sensors and biosensors, and until now they are most commonly used, especially in commercially available sensors, mainly for clinical and environmental analyses. An intensive development of optical sensors (optodes) in recent 30 years has resulted in numerous designs and commercial products, which are increasingly competitive to electrochemical sensors. A more limited importance, especially as mass production is concerned and applications in routine analyses, have thermal and mass-sensitive sensors and biosensors. 

The history of electrochemical sensors began in the thirties of the twentieth century, when the pH-sensitive glass electrode was deployed, but no noteworthy development was carried out till the middle of that century. In 1956, Clark invented his oxygen-sensor based on a Ft electrode in 1959, the first piezoelectric mass-deposition sensor (a quartz crystal microbal-ance) was produced. In the sixties, the first biosensors (Clark and Lyons, 1962) and the first metal oxide semiconductor-based gas sensors (Taguchi, 1962) started to appear. 

Abstract Brief historic introduction precedes presentation of main types of transducers used in sensors including electrochemical, optical, mass sensitive, and thermal devices. Review of chemical sensors includes various types of gas sensitive devices, potentiometric and amperometric sensors, and quartz microbalance applications. Mechanisms of biorecognition employed in biosensors are reviewed with the method of immobilization used. Some examples of biomimetic sensors are also presented. 

Since hydrogen peroxide is the product of reactions catalysed by a huge number of oxidase enzymes and is essential in food, pharmaceutical, and envitonmental analysis, its detection was and remains a necessity. Many attempts have been made in order to develop a biosensor that would be sensitive, stable, inexpensive and easy to handle. The most popular and efficient of them are amperometric enzyme biosensors, which utihsed different types of mediators and enzymes, mosdy peroxidase and catalase. Unfortunately many of the sensors developed do not mea the requirements for a practical device, which has a balance of technological charaaeristics (sensitivity, reliability, stability) and commercial adaptability (easy of mass production and low price). Thus a window of opportunity still remains open for future development. We hope that the present work will inspire other researches for further advances in the area of biosensors, in particular sensors for detection of such an important analyte as hydrogen peroxide. 

A piezoelectric biosensor, for the detection of several organophosphorus pesticides was developed (Halamek et al., 2005). The sensor was based on the immobilization of a reversible inhibitor of cholinesterase on the surface of the sensor. The binding of AChE to this inhibitor was monitored with a mass-sensitive piezoelectric quartz crystal. In the presence of an inhibiting substance in the sample, the binding of the enzyme to the immobilized compound was reduced, and the decrease of mass change was proportional to the concentration of the analyte in the sample. This sensor was applied to the determination of pesticides in river water samples. 

Aptamer-based biosensors, also called aptasensor have gain a wide interest in the last years due to the advantages of aptamers compared to antibodies. Similar to antibodies, a variety of immobilization methods is available to bind aptamers to the sensor element. Aptasensors can be coupled to an electrochemical, optical or mass-sensitive transducer [13]. One of the successful examples for aptasensor was the detection of thrombin which was widely investigated [14]. Xiao et al. [15] have made an interesting development a redox compound (methylene blue) was inserted into the thrombin aptamer. When the target bound to the aptamer, the induced conformation change inhibited the electron transfer from the methylene blue to the electrode. This change could be detected amperometrically. 

Usually in the operation of biosensors the flow conditions are adjusted to provide a mass transfer rate from the solution to the membrane system which is fast as compared with the internal mass transfer (exception implanted sensors). On the other hand, variations of the diffusion resistance of the semipermeable membrane are being used to optimize the sensor performance. A semipermeable membrane with a molecular cutoff of 10 000 and a thickness of 10 pm only slightly influences the response time and sensitivity. In contrast, thicker membranes, e.g. of polyurethane or charged material, significantly enhance the measuring time, but may also lead to an extension of the linear measuring range. 

The direct fixation of the biocatalyst to the sensitive surface of the transducer permits the omission of the inactive semipermeable membranes. However, the advantages of the membrane technology are also lost, such as the specificity of permselective layers and the possibility of affecting the dynamic range by variation of the diffusion resistance. Furthermore, the membrane technology has proved to be useful for reloading reusable sensors with enzyme. In contrast, direct enzyme fixation is mainly suited to disposable sensors. This is especially valid for carbon-based electrodes, metal thin layer electrodes printed on ceramic supports, and mass-produced optoelectronic sensors. Field effect transistors may also be envisaged as basic elements of disposable biosensors. 

Our goal is the development of a "user friendly" biosensor for small molecules such as pesticides. To reach this goal the sensor must have a number of characteristics. These include specificity, sensitivity, accuracy, precision, ruggedness and manufacturability. While they are for the most part self-explanatory, the characteristic of manufacturabilty deserves further comment. The best sensor is of little use if it cannot be mass produced at a reasonable cost. For this reason our search for a transduction mechanism for a biosensor has concentrated where possible on well proven technologies that lend themselves to mass production. The biosensor we present here combines two well established technologies antibodies and microelectronics. 

Campbell, G. A., Mutharasan, R. PEMC sensor s mass change sensitivity is 20 pg/ Hz under liquid immersion. Biosensors and Bio electronics 2006, 22 (1), 35—41... 

In spite of these limitations and problems, investment trends in sensors appear to have stabilized in the mid-1990s, and should increase steadily into the next century. The reason for this investment turnaround appears to be the maturing of chemical and biosensor companies and development efforts. Lead investigators in these efforts are more aware of the needs to develop sensors which are easily scaled up and mass produced. In addition, improved methods for the immobilization and stabilization of sensor active surfaces are being developed which promise both increased sensitivity/specificity for the sensors and simple and cost-effective mass production of highly stable sensors. 

Biosensor instruments such as Biacore (General Electric) exploit the sensitivity of a surface plasmon resonance response to the mass localised near the surface of a sensor chip. Various approaches can be used for kinases. Inhibition in solution assays involve immobilisation of a target definition compound (TDQ on the sensor surface.13,30 A buffer containing the kinase is flowed over the surface so that the protein is able to bind to the immobilised TDC, giving a signal. When test compounds are included in the buffer, they can compete for the TDC-kinase interaction, allowing estimation of Kd. 

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