Biomolecular sensing with light at nanostructured surfaces (original) (raw)
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Semicond. Phys. …, 2009
In this work, we use a nanoimprint lithography fabrication technology to create uniformly-oriented and homogenous noble metal nanoparticle arrays with wellcontrolled size, shape and spacing, which can be the basis platform for the development of Localized Surface Plasmon Resonance (LSPR) sensors for biomolecular detection. Using this approach, we demonstrate proof-of-principle of an optical biosensor to quantify biomolecular interactions in a real-time mode using a UV-visible spectrophotometer. The sensor shows concentration-dependent kinetics of surface adsorption or binding of biomolecules and a capability to monitor antigen-antibody specific reactions, which is demonstrated by the reaction between bovine serum albumin (BSA) and anti-BSA immunoglobulin.
Plasmonics in Biology and Medicine V, 2008
In this work, we aim at enhancing the sensitivity of surface plasmon resonance sensors towards the detection of biomolecule interactions by means of nanopatterning of the sensor surface. Use of nanostructured interfaces in combination with SPR is a promising step towards realizing biosensors with high efficiency and sensitivity. Nanopatterned surfaces enable multi-dimensional control over the behavior of surface-immobilized probe molecules. By means of a combination of self-assembled monolayer technology, colloidal lithography, and reactive ion etching, nanopatterns with either antibody confining or non-confining characteristics were produced and analyzed via photoelectron spectroscopy and infrared reflection absorption spectroscopy. Antibody immobilization on the patterns and subsequent specific binding of antigen was traced in real time by means of a surface plasmon resonance sensor. It was found that confining nanopatterns yield an increase in antibody activity towards antigen capture on surface of up to 120%, depending on the protocol used for their immobilization.
Analytica Chimica Acta, 2012
The immobilisation of biological recognition elements onto a sensor chip surface is a crucial step for the construction of biosensors. While some of the optical biosensors utilise silicon dioxide as the sensor surface, most of the biosensor surfaces are coated with metals for transduction of the signal. Biological recognition elements such as proteins can be adsorbed spontaneously on metal or silicon dioxide substrates but this may denature the molecule and can result in either activity reduction or loss. Self assembled monolayers (SAMs) provide an effective method to protect the biological recognition elements from the sensor surface, thereby providing ligand immobilisation that enables the repeated binding and regeneration cycles to be performed without losing the immobilised ligand, as well as additionally helping to minimise non-specific adsorption. Therefore, in this study different surface chemistries were constructed on SPR sensor chips to investigate protein and DNA immobilisation on Au surfaces. A cysteamine surface and 1%, 10% and 100% mercaptoundeconoic acid (MUDA) coatings with or without dendrimer modification were utilised to construct the various sensor surfaces used in this investigation. A higher response was obtained for NeutrAvidin immobilisation on dendrimer modified surfaces compared to MUDA and cysteamine layers, however, protein or DNA capture responses on the immobilised NeutrAvidin did not show a similar higher response when dendrimer modified surfaces were used.
Topographically Engineered Large Scale Nanostructures for Plasmonic Biosensing
Scientific Reports, 2016
We demonstrate that a nanostructured metal thin film can achieve enhanced transmission efficiency and sharp resonances and use a large-scale and high-throughput nanofabrication technique for the plasmonic structures. The fabrication technique combines the features of nanoimprint and soft lithography to topographically construct metal thin films with nanoscale patterns. Metal nanogratings developed using this method show significantly enhanced optical transmission (up to a one-order-ofmagnitude enhancement) and sharp resonances with full width at half maximum (FWHM) of ~15nm in the zero-order transmission using an incoherent white light source. These nanostructures are sensitive to the surrounding environment, and the resonance can shift as the refractive index changes. We derive an analytical method using a spatial Fourier transformation to understand the enhancement phenomenon and the sensing mechanism. The use of real-time monitoring of protein-protein interactions in microfluidic cells integrated with these nanostructures is demonstrated to be effective for biosensing. The perpendicular transmission configuration and large-scale structures provide a feasible platform without sophisticated optical instrumentation to realize label-free surface plasmon resonance (SPR) sensing.
Plasmonic Nanostructured Devices for Chemical and Biological Sensing
2005
The focus of this NIRT project is to investigate the fundamentals of plasmonic phenomena in nanoscale metallic structures and to explore the use of plasmonic chip technologies in biochemical sensing. We investigate metal nanoaperture arrays as a medium for effective interactions among photons, plasmons, and anlytes, and also as a base structure that provides wavelength-dependent transmission of light. The plasmonic interaction in chemically functionalized nanoaperture arrays offers a new strategy for massively parallel detection of chemical and biological analytes. Modulation of the nanoaperture array's optical response by adsorbed analytes is expected to offer improved sensitivity and selectivity over conventional surface plasmon resonance (SPR) methods, which are widely used and commercialized for analysis in detecting biological and chemical agents. The conventional SPR measurement usually involves bulky optics and high-precision mechanics for angular or wavelength interrogation of metal films in contact with analytes. As such, it is difficult to implement and automate the conventional SPR technique in compact instrumentation. We investigate a new approach to SPR sensing of biochemical agents by exploiting the recent breakthroughs in plasmonics that involve metallic nanostructures. The devices being developed in this program are amenable to miniaturization and integration with a photodetector chip so that chip-scale sensor arrays, which will enable massively parallel detection of many analytes and on-chip processing of information in the electronic domain. Research in the first year of this NIRT project has focused on investigating the fundamental physics of optical interactions in nanoapertured metal layers and on chemically modifying the metal surfaces for biochemical sensing.
Development of plasmonic substrates for biosensing
2008
The transmission of normally incident light through arrays of subwavelength holes (nanoholes) in gold thin films is enhanced at the wavelengths that satisfy the surface plasmon resonance (SPR) condition. Our group has been active on the implementation of schemes for the application of this phenomenon for chemical sensing. For instance, we have shown that the interaction between adsorbates with nanoholes modified the SP resonance conditions, leading to a shift in the wavelength of maximum transmission. The output sensitivity of this substrate was found to be 400 nm RIU-1 (refractive index units), which is comparable to other grating-based surface plasmon resonance devices. The array of nanoholes was also integrated into a microfluidic system and the characteristics of the solution flow and detection systems were evaluated. In this work, we will concentrate on improving the efficiency of the nanohole arrays for applications in chemical in chemical sensing. Attempts to improve the sensitivity of the device will be discussed. In-hole sensing is suggested as an alternative to decrease the number of probe molecules, and enhance sensitivity. A biaxial sensing scheme will also be introduced. The biaxial scheme allows for polarization-modulation detection that can account for background fluctuations. A flow-through approach should lead to an optimized transport situation of the analytes to the immobilized species at the surface, which should significantly improve the time and sensitivity of the analysis. Finally, we will discuss the implementation of multiplexing detection using these arrays. Multiplexing detection in zero-order transmission is simpler to implement than the common multiplexing imaging from angle-resolved SPR.
Sensors
In this work we present a surface plasmon resonance sensor based on enhanced optical transmission through sub-wavelength nanohole arrays. This technique is extremely sensitive to changes in the refractive index of the surrounding medium which result in a modulation of the transmitted light. The periodic gold nanohole array sensors were fabricated by high-throughput thermal nanoimprint lithography. Square periodic arrays with sub-wavelength hole diameters were obtained and characterized. Using solutions with known refractive index, the array sensitivities were obtained. Finally, protein absorption was monitored in real-time demonstrating the label-free biosensing capabilities of the fabricated devices.
A surface plasmon resonance array biosensor based on spectroscopic imaging
Biosens Bioelectron, 2001
We have developed a multi-element transduction system which combines conventional SPR spectroscopy with one-dimensional SPR microscopy to create an effective platform for monitoring binding events on macro-or micro-patterned receptor arrays created on disposable sensor chips. This creates an effective platform for monitoring simultaneous binding events on each of the regions patterned with the receptors. This system has been specifically designed with commercially available components to allow relatively easy duplication. Furthermore, this system can use a proven, simple method to compensate for changes in the bulk index of refraction of the solution containing the analytes due to changes in temperature or solute concentration with simple modifications to the sensor chips alone. Preliminary results demonstrate how this system can be used to monitor several independent biospecific binding events simultaneously.
Localized surface plasmon resonance biosensors for real-time biomolecular binding study
A sensitive and low-cost microfluidic integrated biosensor is developed based on the localized surface plasmon resonance (LSPR) properties of gold nanoparticles, which allows label-free monitoring of biomolecular interactions in real-time. A novel quadrant detection scheme is introduced which continuously measures the change of the light transmitted through the nanoparticlecoated sensor surface. Using a green light emitting diode (LED) as a light source in combination with the quadrant detection scheme, a resolution of 10 −4 in refractive index units (RIU) is determined. This performance is comparable to conventional LSPR-based biosensors. The biological sensing is demonstrated using an antigen/antibody (biotin/ anti-biotin) system with an optimized gold nanoparticle film. The immobilization of biotin on a thiol-based selfassembled monolayer (SAM) and the subsequent affinity binding of anti-biotin are quantitatively detected by the microfluidic integrated biosensor and a detection limit of 270 ng/mL of anti-biotin was achieved. The microfluidic chip is capable of transporting a precise amount of biological samples to the detection areas to achieve highly sensitive and specific biosensing with decreased reaction time and less reagent consumption. The obtained results are compared with those measured by a surface plasmon resonance (SPR)-based Biacore system for the same binding event. This study demonstrates the feasibility of the integration of LSPR-based biosensing with microfluidic technologies, resulting in a low-cost and portable biosensor candidate compared to the larger and more expensive commercial instruments.
Scientific Reports, 2014
We demonstrate a high-throughput biosensing device that utilizes microfluidics based plasmonic microarrays incorporated with dual-color on-chip imaging toward real-time and label-free monitoring of biomolecular interactions over a wide field-of-view of .20 mm 2 . Weighing 40 grams with 8.8 cm in height, this biosensor utilizes an opto-electronic imager chip to record the diffraction patterns of plasmonic nanoapertures embedded within microfluidic channels, enabling real-time analyte exchange. This plasmonic chip is simultaneously illuminated by two different light-emitting-diodes that are spectrally located at the right and left sides of the plasmonic resonance mode, yielding two different diffraction patterns for each nanoaperture array. Refractive index changes of the medium surrounding the near-field of the nanostructures, e.g., due to molecular binding events, induce a frequency shift in the plasmonic modes of the nanoaperture array, causing a signal enhancement in one of the diffraction patterns while suppressing the other. Based on ratiometric analysis of these diffraction images acquired at the detector-array, we demonstrate the proof-of-concept of this biosensor by monitoring in real-time biomolecular interactions of protein A/G with immunoglobulin G (IgG) antibody. For high-throughput on-chip fabrication of these biosensors, we also introduce a deep ultra-violet lithography technique to simultaneously pattern thousands of plasmonic arrays in a cost-effective manner.