Label-free Detection Of Biomolecular Interactions Research Articles

Silicon-on insulator based thin-film resistor for chemical and biological sensor applications.

Efficient detection of specific or nonspecific interactions at solid ± liquid interfaces is becoming increasingly important for a wide variety of applications and technologies, which range from industrial and biomedical applications to basic research. 2] The most prominent example of applications in basic research is the label-free detection of biomolecular interactions. There is growing need for new detection schemes, as the common fluorescent labeling techniques are limiting the applicability of DNA or protein arrays. Increasingly sophisticated techniques are being developed to provide versatile techniques for labelfree detection methods. 5] The main requirement for new technologies is the highly sensitive and specific detection of molecules. At the same time, for the applicability of the technique towards screening of biomolecular interactions, the potential of simultaneous parallel detection is mandatory. Several different approaches have been developed to address these requirements. For the electrical detection of molecular interactions, physical principles of field-effect transistors are used in most cases: Variations of the surface potential induce changes in the charge carrier concentration and thus in the conductivity of the semiconductor. The most extensively studied technique to date is the technology of ion-sensitive field-effect transistors (ISFETs), which have been shown to be versatile tools for detecting chemical and enzymatic reactions. The direct electrical detection of cell signaling was realized with recently developed semiconductor chips. 8] The capacitive detection of inversion layers in silicon structures has successfully been used to monitor the hybridization of DNA molecules. A similar approach with a biofunctionalized, porous silicon electrolyte ± insulator ± semiconductor (EIS) structure as a sensing device was used to detect biomolecules, such as penicillin, with a sensitivity down to 10 nM. Here, we present a device based on silicon-on-insulator (SOI) substrates that enables the detection of changes of electrolyte concentrations and of small numbers of charged biomolecules. In the SOI substrates the conducting layer is limited to a thin surface layer, covered by a thin native oxide layer. Hence, the conductivity of this thin conductive layer is strongly dependent on variations of the surface potential and the distribution of the surface states, which results in variations of the space charge region. We utilized a four-point resistance measurement in a hallbar geometry to determine the conductivity of the sensing layer. A variation of the salt concentration of the electrolyte could be detected over five magnitudes and an excellent agreement with the Grahame equation was found. The unspecific adsorption of poly-L-lysine was detectable at concentrations of 1 nM (80 ngmL ). The measurements showed that variations of surface charges of 0.01 e per nm, or one electronic charge per 100 nm, could be detected by the device. For the experiments, commercially available SOI wafers (ELTRAN, Canon) were used. The silicon layer in these wafers was 30 nm thick and was slightly doped with boron (10 cm ). To control the concentration of charge carriers in this layer, a voltage was applied to the backgate of the substrate. For some experiments, this upper silicon layer was overgrown by molecular beam epitaxy (MBE) with a 50 nm thick, single crystalline layer of doped silicon. The p-doping concentration of boron was 10 cm 3 or 10 cm . A sketch of the SOI device is given in Figure 1. In the subsequent steps, the silicon layer was patterned

Colloidal gold submonolayer-coated thin-film glass plates for waveguide-coupled surface plasmon resonance sensors.

A novel optical sensor based on spectroscopic measurement of the plasmon absorption of a colloidal gold submonolayer immobilized upon a planar waveguide has been developed for label-free detection of biomolecular interactions at the sensor's surface. We fabricated the sensor by locally modifying a 50-microm-thick glass plate with hemoglobin (Hb) and then self-assembling gold colloids from the aqueous solution onto the Hb-modified area of the glass plate. Polychromatic light from a xenon-arc lamp was launched into the thin-film glass plate by use of a broadband fiber-coupling method. With the use of a CCD detector to monitor the light beam emitted from an end face of the glass plate, the plasmon absorption spectrum of the colloidal gold submonolayer was determined to depend on the polarization states of the guided light and to change with the refractive index of the medium in contact with the colloids. In addition to simplicity of fabrication and the ease of use, the sensor yields a larger absorbance sensitivity than the normal transmission measurement.