With recent advances in nanotechnology, great progress has been made in biosensors based on nanomaterials, but there are still numerous challenges to overcome. We describe nanomaterial-based biosensors for researchers new to the field, paying particular attention to metal nanoparticles and carbon nanotube (CNT)-based label-free approaches. Label-free monitoring of biorecognition events provides a promising platform, which is simple, cost-effective, and requires no external modification to biomolecules. Using examples from recent reports, we illustrate the diversity of biological recognition events and the range of experimental techniques employed for metal-nanoparticle-based and label-free characterization.

Nanomaterial-based electrochemical biosensors for medical applications

Label-free optical biosensors are an intriguing option for the analyses of many analytes, as they offer several advantages such as high sensitivity, direct and real-time measurement in addition to multiplexing capabilities. However, development of label-free optical biosensors for small molecules can be challenging as most of them are not naturally chromogenic or fluorescent, and in some cases, the sensor response is related to the size of the analyte. To overcome some of the limitations associated with the analysis of biologically, pharmacologically, or environmentally relevant compounds of low molecular weight, recent advances in the field have improved the detection of these analytes using outstanding methodology, instrumentation, recognition elements, or immobilization strategies. In this review, we aim to introduce some of the latest developments in the field of label-free optical biosensors with the focus on applications with novel innovations to overcome the challenges related to small molecule detection. Optical label-free methods with different transduction schemes, including evanescent wave and optical fiber sensors, surface plasmon resonance, surface-enhanced Raman spectroscopy, and interferometry, using various biorecognition elements, such as antibodies, aptamers, enzymes, and bioinspired molecularly imprinted polymers, are reviewed.

Optical Biosensors for Label-Free Detection of Small Molecules

Reporting biomolecular interactions has become part and parcel of many applications of science towards an in-depth understanding of disease and gene regulation. Apart from that, in diagnostic applications where biomolecules (antibodies and aptamers) are vastly applied, meticulous monitoring of biomolecular interaction is vital for clear-cut diagnosis. Several currently available methods of analyzing the interaction of the ligands with the appropriate analytes are aided by labeling using fluorescence or luminescence techniques. However, labeling is cumbersome and can occupy important binding sites of interactive molecules to be labeled, which may interfere with the conformational changes of the molecules and increase non-specificity. Optical-based sensing can provide an alternative way as a label-free procedure for monitoring biomolecular interactions. Optical sensors affiliated with different operating principles, including surface plasmon changes, scattering and interferometry, can impart a huge impact for in-house and point-of-care applications. This optical-based biosensing permits real-time monitoring, obviating the use of hazardous labeling molecules such as radioactive tags. Herein, label-free ways of reporting biomolecular interactions by various optical biosensors were gleaned.

Label-free methods of reporting biomolecular interactions by optical biosensors

We present a high-throughput screening Raman spectroscopy (HTS-RS) platform for a rapid and label-free macromolecular fingerprinting of tens of thousands eukaryotic cells. The newly proposed label-free HTS-RS platform combines automated imaging microscopy with Raman spectroscopy to enable a rapid label-free screening of cells and can be applied to a large number of biomedical and clinical applications. The potential of the new approach is illustrated by two applications. (1) HTS-RS-based differential white blood cell count. A classification model was trained using Raman spectra of 52 218 lymphocytes, 48 220 neutrophils, and 7 294 monocytes from four volunteers. The model was applied to determine a WBC differential for two volunteers and three patients, producing comparable results between HTS-RS and machine counting. (2) HTS-RS-based identification of circulating tumor cells (CTCs) in 1:1, 1:9, and 1:99 mixtures of Panc1 cells and leukocytes yielded ratios of 55:45, 10:90, and 3:97, respectively. Because ...

High-Throughput Screening Raman Spectroscopy Platform for Label-Free Cellomics

Optical Biosensors for Therapeutic Drug Monitoring.

Potential of label-free detection in high-content-screening applications.

Reflectometry is classified in comparison to the commercialized refractometric surface plasmon resonance (SPR). The advantages of direct optical detection depend on a sophisticated surface chemistry resulting in negligible nonspecific binding and high loading with recognition sites at the biopolymer sensitive layer of the transducer. Elaborate details on instrumental realization and surface chemistry are discussed for optimum application of reflectometric interference spectroscopy (RIfS). A standard protocol for a binding inhibition assay is given. It overcomes principal problems of any direct optical detection technique.

Reflectometric Interference Spectroscopy

Adaptive compensation of the transmission errors in rack-and-pinion drives

Various applications of photodetectors in bioanalytics, medicine and pharmaceutical research ask for low-cost, disposable sensor systems. Amorphous silicon (a-Si) based thin film photodetectors offer the unique chance of direct low-temperature deposition on plastic substrates, and of a precise application-specific tailoring of their optical properties and spectral sensitivity. Here we report on the first steps of developing integrated thin film detectors for a label-free point-of-care testing (POCT) in a university hospital. Key features are the dynamic adjustment of the spectral response of a p–i–i–n photodiode by a variable read-out voltage, and the monolithic integration of the a-Si based detector into the reflectometric interference spectroscopy (RIfS) setup. This contribution presents the first successful detection of the growth of 12 nm thin protein layers with these detectors. Experimental and modeling results of the a-Si based p–i–i–n photodetectors show good agreement.

Amorphous silicon based p–i–i–n photodetector detects 12 nm thin protein layers

The invention relates to a carrier for a thin layer and a method for the analysis of molecular interactions on and/or in such a thin layer. A thin layer disposed on a carrier is illuminated with electromagnetic radiation from at least one radiation source and a reflected radiation part on boundary surfaces of the thin layer is detected by means of an optoelectronic converter that converts the detected radiation into a frequency- and intensity-dependant photocurrent. A reading voltage is applied to the optoelectronic converter. By changing the reading voltage, the spectral sensitivity of the optoelectronic converter is varied such that a substantially constant photocurrent is obtained. Alternatively or in addition to varying the spectral sensitivity by changing the reading voltage, the reflected radiation part is detected with an optoelectronic converter that is designed as a sensor layer in the carrier. The carrier is particularly characterized in that it comprises a substrate on which at least one sensor layer with optoelectronic properties is disposed.

Analysis of molecular interactions on and/or in thin layers

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