Biomolecular interaction detection

SRU Biosystems (Woburn, MA) applied the principle of the colorimetric resonant grating reflection in the so-called BIND (Biomolecular Interaction Detection) system that allows parallel readout in 96- and 384-well microplate format (http //www.srubiosystems.com). A grating with a period shorter than the reflected wavelength range (550 nm) and a depth in the range of 170 nm is structured by... 

R Estrela, A.G. Stewart, F. Yan, and P. Migliorato, Field effect detection of biomolecular interactions. Electrochim. Acta 50, 4995-5000 (2005). 

P. Estrela, P. Migliorato, H. Takiguchi, H. Fukushima, and S. Nebashi, Electrical detection of biomolecular interactions with metal-insulator-semiconductor diodes. Biosens. Bioelectron. 20, 1580-1586 (2005). 

Immunosensors have been developed commercially mostly for medical purposes but would appear to have considerable potential for food analysis. The Pharmacia company has developed an optical biosensor, which is a fully automated continuous-flow system which exploits the phenomenon of surface plasmon resonance (SPR) to detect and measure biomolecular interactions. The technique has been validated for determination of folic acid and biotin in fortified foods (Indyk, 2000 Bostrom and Lindeberg, 2000), and more recently for vitamin Bi2. This type of technique has great potential for application to a wide range of food additives but its advance will be linked to the availability of specific antibodies or other receptors for the various additives. It should be possible to analyse a whole range of additives by multi-channel continuous flow systems with further miniaturisation. 

Time-resolved RET is capable of very sensitive detection of DNA hybridization. With a lanthanide chelate as the donor and an organic fluorophore like tetramethylrhodamin as the acceptor, time-resolved measurements can indicate the hybridization by strong changes in the intensity decay of the donor [186]. The development of new dyes for time-resolved RET with improved properties still is a major task [187,188]. But, so far, the detection of biomolecular interactions by time-resolved RET has not entered real applications in the DNA or protein array market. 

The use of ECL processes for the detection of biological compounds is a rapidly growing area of interest, both for quantitation of analytes and to measure biomolecular interactions. By using ECL active chromophores as labels for biological compounds, a variety of applications is possible, including assays for enzymatic activity, binding assays, immunoassays, and nucleic acid probe assays. 

The versatility of the SPR technique has been shown by a vast amount of publications in the past decades the method has matured into a well-accepted analytical tool for the characterization of interfaces and thin films as well as for the sensitive detection of interfacial biomolecular interaction. With a significant input from engineering, SPR has reached a decent signal-to-noise level with a lower limit for a reliable signal detection corresponding to an effective layer of about 0.3 A [6], which is sufficient for most thin film studies. However, the intrinsic label-free characteristic of SPR detection technique still imposes limitation on further sensitivity improvement, especially if the analysis involves small molecules. 

In contrast to SPFS, SPR, and SPDS are tools that can study biomolecular interactions without external labels. They share the same category of label-free biosensors with the reflectometry interference spectroscopy (RIfS) [46], waveguide spectroscopy [47], quartz crystal microbalance (QCM) [48], micro-cantilever sensors [49], etc. Although the label-free sensors cannot compete with SPFS in terms of sensitivity [11], they are however advantageous in avoiding any additional cost/time in labeling the molecules. In particular, the label-free detection concept eliminates undue detrimental effects originating from the labels that may interfere with the fundamental interaction. In this sense, it is worthwhile to develop and improve such sensors as instruments complementary to those ultra-sensitive sensors that require labels. 

Hashimoto S, Isobe T, Natsume T (2007) Biomolecular interaction analysis coupled with mass spectrometry to detect interacting proteins. In Walker JM (ed) The proteomics protocols handbook. Humana Press, Totowa, NJ... 

Beusink JB, Lokate AMC, Besselink GAJ, Pmijn GJM, Schasfoort RBM (2008) Anglescanning SPR imaging for detection of biomolecular interactions on microarrays. Biosens Bioelectron 23 839-844... 

HTRF is a homogeneous technology which combines an FRET process with time-resolved fluorescence detection to probe biomolecular interactions. This combination is made possible through the use of a long lifetime fluorescent FRET donor, a lanthanide cryptate. Cryptates are formed by the inclusion of a rare earth ion e.g. 

Biomolecular interaction analysis (BIA) is a relatively new technique which enables the detection of biomolecules and the monitoring of interactions between two or more species to be carried out in real time, without the use of labels. The detection principle used depends on the phenomenon of Surface Plasmon Resonance (SPR). 

Yeung, D., Gill, A., Maule, C. H., Davies, R. J. (1995) Detection and quantification of biomolecular interactions with optical biosensors. TrAC-Trends in Analytical Chemistry 14 49-56. 

Ochsenkuehn MA, Campbell CJ (2010) Probing biomolecular interactions using surface enhanced raman spectroscopy label-free protein detection using a g-quadmplex dna aptamer. Chem Comm 16 2799-2801... 

Other less common DNA sensors have been described, such as the use of magnetic microbeads on a solid substrate, to detect and characterize many individual biomolecular interaction events simultaneously using the concept of measuring changes in the intermolecular forces by arrays of microfabri-cated magnetoresistive DNA sensors, as developed by Baselt et al. [18]. 

Optical biosensors can be defined as sensor devices which make use of optical principles for the transduction of a biochemical interaction into a suitable output signal. The biomolecular interaction on the sensor surface modulates the light characteristics of the transducer (i.e., intensity, phase, polarization, etc.), and the biosensing event can be detected by the change in diverse optical properties such as absorption, fiuorescence, luminescence or refractive index, among others. 

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