Photonic crystals: A platform for label-free and enhanced fluorescence biomolecular and cellular assays

2008 ◽  
Vol 1133 ◽  
Author(s):  
Brian T. Cunningham ◽  
Leo Chan ◽  
Patrick C. Mathias ◽  
Nikhil Ganesh ◽  
Sherine George ◽  
...  

Abstract Photonic crystal surfaces represent a class of resonant optical structures that are capable of supporting high intensity electromagnetic standing waves with near-field and far-field properties that can be exploited for high sensitivity detection of biomolecules and cells. While modulation of the resonant wavelength of a photonic crystal by the dielectric permittivity of adsorbed biomaterials enables label-free detection, the resonance can also be tuned to coincide with the excitation wavelength of common fluorescent tags - including organic molecules and semiconductor quantum dots. Photonic crystals are also capable of efficiently channeling fluorescent emission into a preferred direction for enhanced extraction efficiency. Photonic crystals can be designed to support multiple resonant modes that can perform label free detection, enhanced fluorescence excitation, and enhanced fluorescence extraction simultaneously on the same device. Because photonic crystal surfaces may be inexpensively produced over large surface areas by nanoreplica molding processes, they can be incorporated into disposable labware for applications such as pharmaceutical high throughput screening. In this talk, the optical properties of surface photonic crystals will be reviewed and several applications will be described, including results from screening a 200,000-member chemical compound library for inhibitors of protein-DNA interactions, gene expression microarrays, and high sensitivity of protein biomarkers.

2010 ◽  
Vol 15 (2) ◽  
pp. 120-135 ◽  
Author(s):  
Brian T. Cunningham

Photonic crystal (PC) surfaces can be designed to provide a wide range of functions that are used to perform biochemical and cell-based assays. Detection of the optical resonant reflections from PC surfaces enables high sensitivity label-free biosensing, whereas the enhanced electromagnetic (EM) fields that occur at resonant wavelengths can be used to enhance the detection sensitivity of any surface-based fluorescence assay. Fabrication of PCs from inexpensive plastic materials over large surface areas enables them to be incorporated into standard formats that include microplates, microarrays, and microfluidic channels. This report reviews the design of PC biosensors, their associated detection instrumentation, and biological applications. Applications including high-throughput screening of small molecules, cell membrane integrin activation, gene expression analysis, and protein biomarker detection are highlighted. Recent results in which PC surfaces are used for enhancing the detection of surface-enhanced Raman spectroscopy, and the development of high-resolution PC-based laser biosensors are also described.


2014 ◽  
Vol 492 ◽  
pp. 301-305 ◽  
Author(s):  
Faida Bougriou ◽  
Touraya Boumaza ◽  
Mohamed Bouchemat

The use of photonic crystals (PCS) in biosensor applications has lead to the development of highly sensitive and selective microfluidic sensor elements. Two main advantages of these devices for sensing applications are their high sensitivity and their reduced size, which makes it possible, in one hand, to detect very small analytes without the need of markers (label-free detection), and to integrate many of these devices on a single chip to perform a multi-parameter detection on the other hand. In the present paper, we analyze the design of a highly sensitive microfluidic sensors based on 2D photonic crystal slab waveguide formed by increasing the radii of air holes localized at each side of the line defect and filling with homogenous de-ionized water (nc =1.33). The transmission spectrum of the sensor has been obtained with the use of Finite Difference Time Domain (FDTD) method and it has been observed that a 306 nm wavelength position of the lower band edge shift was observed corresponding to a sensitivity of more than 927 nm per refractive index unit (RIU). Development of microfluidic sensor designs that enhance sensitivity is especially important because it allows detection of lower concentrations of analytes.


2009 ◽  
Vol 17 (15) ◽  
pp. 13222 ◽  
Author(s):  
Ian D. Block ◽  
Patrick C. Mathias ◽  
Nikhil Ganesh ◽  
Sarah I. Jones ◽  
Brian R. Dorvel ◽  
...  

2014 ◽  
Vol 105 (6) ◽  
pp. 063118 ◽  
Author(s):  
Daquan Yang ◽  
Shota Kita ◽  
Feng Liang ◽  
Cheng Wang ◽  
Huiping Tian ◽  
...  

2017 ◽  
Vol 22 (10) ◽  
pp. 1203-1210 ◽  
Author(s):  
Katrin Beeman ◽  
Jens Baumgärtner ◽  
Manuel Laubenheimer ◽  
Karlheinz Hergesell ◽  
Martin Hoffmann ◽  
...  

Mass spectrometry (MS) is known for its label-free detection of substrates and products from a variety of enzyme reactions. Recent hardware improvements have increased interest in the use of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS for high-throughput drug discovery. Despite interest in this technology, several challenges remain and must be overcome before MALDI-MS can be integrated as an automated “in-line reader” for high-throughput drug discovery. Two such hurdles include in situ sample processing and deposition, as well as integration of MALDI-MS for enzymatic screening assays that usually contain high levels of MS-incompatible components. Here we adapt our c-MET kinase assay to optimize for MALDI-MS compatibility and test its feasibility for compound screening. The pros and cons of the Echo (Labcyte) as a transfer system for in situ MALDI-MS sample preparation are discussed. We demonstrate that this method generates robust data in a 1536-grid format. We use the MALDI-MS to directly measure the ratio of c-MET substrate and phosphorylated product to acquire IC50 curves and demonstrate that the pharmacology is unaffected. The resulting IC50 values correlate well between the common label-based capillary electrophoresis and the label-free MALDI-MS detection method. We predict that label-free MALDI-MS-based high-throughput screening will become increasingly important and more widely used for drug discovery.


2017 ◽  
Vol 22 (10) ◽  
pp. 1246-1252 ◽  
Author(s):  
Kishore Kumar Jagadeesan ◽  
Simon Ekström

Recently, mass spectrometry (MS) has emerged as an important tool for high-throughput screening (HTS) providing a direct and label-free detection method, complementing traditional fluorescent and colorimetric methodologies. Among the various MS techniques used for HTS, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) provides many of the characteristics required for high-throughput analyses, such as low cost, speed, and automation. However, visualization and analysis of the large datasets generated by HTS MALDI-MS can pose significant challenges, especially for multiparametric experiments. The datasets can be generated fast, and the complexity of the experimental data (e.g., screening many different sorbent phases, the sorbent mass, and the load, wash, and elution conditions) makes manual data analysis difficult. To address these challenges, a comprehensive informatics tool called MALDIViz was developed. This tool is an R-Shiny-based web application, accessible independently of the operating system and without the need to install any program locally. It has been designed to facilitate easy analysis and visualization of MALDI-MS datasets, comparison of multiplex experiments, and export of the analysis results to high-quality images.


2019 ◽  
Author(s):  
Frank Biedermann ◽  
Garima Ghale, Ghale ◽  
Andreas Hennig ◽  
Werner M. Nau

<p>The spatiotemporally resolved monitoring of membrane translocation, <i>e.g.,</i> of drugs or toxins, has been a long-standing goal. Herein, we introduce the fluorescent artificial receptor-based membrane assay (FARMA), a facile, label-free method. With FARMA, the permeation of more than hundred organic compounds (drugs, toxins, pesticides, neurotransmitters, peptides, etc.) through vesicular phospholipid bilayer membranes has been monitored in real time (µs-h time scale) and with high sensitivity (nM-µM concentration), affording permeability coefficients across an exceptionally large range from 10<sup>–9</sup>‑10<sup>–3</sup> cm s<sup>–1</sup>. From a fundamental point of view, FARMA constitutes a powerful tool to assess structure-permeability relationships and to test biophysical models for membrane passage. From an applied perspective, FARMA can be extended to high-throughput screening by adaption of the microplate reader format, to spatial monitoring of membrane permeation by microscopy imaging, and to the compartmentalized monitoring of enzymatic activity.<b></b></p>


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