Silicon photonic crystal nanocavity-coupled waveguides for error-corrected optical biosensing

A photonic crystal (PhC) waveguide based optical biosensor capable of label-free and error-corrected sensing was investigated in this study. The detection principle of the biosensor involved shifts in the resonant mode wavelength of nanocavities coupled to the silicon PhC waveguide due to changes in ambient refractive index. The optical characteristics of the nanocavity structure were predicted by FDTD theoretical methods. The device was fabricated using standard nanolithography and reactive-ion-etching techniques. Experimental results showed that the structure had a refractive index sensitivity of 10(-2) RIU. The biosensing capability of the nanocavity sensor was tested by detecting human IgG molecules. The device sensitivity was found to be 2.3±0.24×10(5) nm/M with an achievable lowest detection limit of 1.5 fg for human IgG molecules. Additionally, experimental results demonstrated that the PhC devices were specific in IgG detection and provided concentration-dependent responses consistent with Langmuir behavior. The PhC devices manifest outstanding potential as microscale label-free error-correcting sensors, and may have future utility as ultrasensitive multiplex devices.     

Porous silicon-based biosensor for pathogen detection

A porous silicon-based biosensor for rapid detection of bacteria was fabricated. Silicon (0.01 ohmcm, p-type) was anodized electrochemically in an electrochemical Teflon cell containing ethanoic hydrofluoric acid solution to produce sponge-like porous layer of silicon. Anodizing conditions of 5 mA/cm2 for 85 min proved best for biosensor fabrication. A single-tube chemiluminescence-based assay, previously developed, was adapted to the biosensor for detection of Escherichia coli. Porous silicon chips were functionalized with a dioxetane-Polymyxin B (cell wall permeabilizer) mixture by diffusion and adsorption on to the porous surface. The reaction of beta-galactosidase enzyme from E. coli with the dioxetane substrate generated light at 530 nm. Light emission for the porous silicon biosensor chip with E. coli was significantly greater than that of the control and planar silicon chip with E. coli (P<0.01). Sensitivity of the porous silicon biosensor was determined to be 101-102 colony forming units (CFU) of E. coli. The porous silicon-based biosensor was fabricated and functionalized to successfully detect E. coli and has potential applications in food and environmental testing.     

On the Performance of Highly Sensitive and Accurate Graphene-on-Aluminum and Silicon-Based SPR Biosensor for Visible and Near Infrared

We demonstrate the numerical analysis of surface plasmon resonance biosensor based on graphene on aluminum and silicon. Employing matrix method, it is found that the proposed sensor exhibits high imaging sensitivity ～400 RIU^?1 to 550 RIU^?1 in a large dynamic range from visible to near IR region. It is observed that the application of monolayer or bilayer graphene over aluminum not only protects it from oxidation but also enhances the adsorption of biomolecules, which results in the detection of large refractive indices ranging from aqueous solution to biomolecules (refractive index 1.330 to 1.480) with overall high performance in terms of imaging sensitivity and detection accuracy.     

Biosensing under an applied voltage using optical waveguide lightmode spectroscopy

An applied dc voltage offers a means of controlling immobilization during biosensor fabrication and detection during biosensing application. We present a method to directly and continuously measure the adsorption of biomacromolecules or other polyelectrolytes, under an applied potential difference, based on optical waveguide lightmode spectroscopy (OWLS). An indium tin oxide (ITO) film of thickness ca. 10 nm coated onto a silicon titanium oxide (STO) waveguiding film serves as the working (sensing) electrode. We observe the effective refractive index of the 0th transverse electric guided mode to increase significantly in the presence of an applied potential due to charging of the interfacial double layer and, possibly, modest electrochemical oxidation. Adsorption from solution onto the ITO electrode is detected by a further increase in the effective refractive index. We achieve accurate detection by employing an optical model in which the STO and ITO layers are combined into a single waveguiding film. No improvement is found using models treating the ITO as a separate layer, either dielectric or conducting. Using this method, we find the adsorption of human serum albumin and horse heart cytochrome c to be considerably enhanced in the presence of an applied potential exceeding 1 V. We attribute this behavior to adsorption at positions on the protein molecules of complementary charge.     

P450-based porous silicon biosensor for arachidonic acid detection

A porous silicon biosensor based on P450 enzyme for arachidonic acid detection was developed. A new transduction method is presented with a simultaneous measurement of refractive index and fluorescence intensity changes when the analyte is binding to an enzyme on the porous silicon surface. A fluorophore bound to a cysteine residue in an allosteric position of the haem domain (BMP) of cytochrome P450 BM3 enhances its fluorescence intensity upon interaction with its substrate arachidonic acid, involved in diseases such as Alzheimer's, liver cancer and cellular inflammation processes. BMP has been anchored on porous silicon surface and the new transduction method has been successfully exploited to develop a biosensor for arachidonic acid, reaching a detection limit of 10 μM arachidonic acid in a dynamic range of 10-200 μM. Moreover, the change of the refractive index has been also monitored at the same time, displaying a higher detection limit of 30 μM. Preliminary test were also conducted in plasma proving the high specificity and selectivity of the sensor even in presence of interferents in the range of 50-100 μM. Here we suggest these two detection systems could be used simultaneously to increase the accuracy and the dynamic range of the sensor avoiding a false positive response.     

Hybridization assay of insect antifreezing protein gene by novel multilayered porous silicon nucleic acid biosensor

A fabrication of a novel simple porous silicon polybasic photonic crystal with symmetrical structure has been reported as a nucleic acid biosensor for detecting antifreeze protein gene in insects (Microdera puntipennis dzhungarica), which would be helpful in the development of some new transgenic plants with tolerance of freezing stress. Compared to various porous silicon-based photonic configurations, porous silicon polytype layered structure is quite easy to prepare and shows more stability; moreover, polybasic photonic crystals with symmetrical structure exhibit interesting optical properties with a sharp resonance in the reflectance spectrum, giving a higher Q factor which causes higher sensitivity for sensing performance. In this experiment, DNA oligonucleotides were immobilized into the porous silicon pores using a standard crosslink chemistry method. The porous silicon polybasic symmetrical structure sensor possesses high specificity in performing controlled experiments with non-complementary DNA. The detection limit was found to be 21.3nM for DNA oligonucleotides. The fabricated multilayered porous silicon-based DNA biosensor has potential commercial applications in clinical chemistry for determination of an antifreeze protein gene or other genes.     

Theoretical Investigation of an Interferometer-type Plasmonic Biosensor Using a Metal-insulator-silicon Waveguide

This work proposes and investigates theoretically a biosensor that is an integrated plasmonic Mach–Zehnder interferometer. The biosensor consists of three sections. The first and third sections are input and output dielectric waveguides whose core is a silicon film. The second section is a combination of a surface plasmon polariton waveguide and a metal-insulator-silicon waveguide, which are separated by a thick gold film. The former and the latter function as sensing and reference arms, respectively. The latter supports a mode whose fields are highly enhanced in a thin insulator, silicon nitride film, and it has relatively small propagation loss. It is shown that the biosensor has insertion loss lower than 2 dB, and that it is very compact since the length of its second section for sensing is shorter than 6 μm. In addition, it is discussed that it can be easily implemented by using simple fabrication processes. Analyzed are the characteristics of sensing a refractive index change of liquid covering the biosensor. Despite its compactness, they are similar to those of previous surface plasmon interferometers. Also, its characteristics as a DNA sensor are analyzed. The analysis demonstrates that the biosensor can detect sensitively target single-stranded DNAs whose total weight is smaller than 10 fg.     

Analysis of the response of planar polarization interferometer to molecular layer formation: fibrinogen adsorption on silicon nitride surface.

The most sensitive optical method of interferometry was exploited for determination of changes in the refractive index following the adsorption of biological molecules onto the solid surface. Instead of having two waveguiding arms (the main and the reference) in traditional Mach-Zhender interferometer, two ortogonal TM and TE modes propagating through the SiO(2)-Si(3)N(4)-SiO(2) waveguide structure were employed in planar polarization interferometer (PPI). Multiperiodic PPI response was, therefore, formed due to the phase shift between TM and TE modes. A matrix simulation procedure was developed in order to investigate the influence of both the refractive index and molecular layer thickness on the PPI response. Nonspecifical binding of fibrinogen to silicon nitride surface was studied as a model object for PPI testing. The results obtained are in good agreement with the known information about fibrinogen adsorption on the different surfaces. An attempt to introduce the concept of 'surface molecular concentration and molecular polariziability' instead of 'molecular layer thickness and refractivity' was undertaken.     

All-Optical Surface Plasmonic Universal Logic Gate Devices

We have introduced optically controlled two-stage cascaded surface plasmonic two-mode interference waveguide structure (having silicon core and silver upper and lower cladding) as universal gates. GaAsInP cladding is used in left and right side of core for optical pulse controlled cladding refractive index modulation which controls propagation of excited modes. The universal logic gate operations have been shown with this structure. These universal gates have potential in development of large-scale integrated optical processor due to its compactness and high fabrication tolerance.     

A Highly Sensitive Dual-Core Photonic Crystal Fiber Based on a Surface Plasmon Resonance Biosensor with Silver-Graphene Layer

A highly sensitive dual-core photonic crystal fiber based on a surface plasmon resonance (PCF-SPR) biosensor with a silver-graphene layer is described. The silver layer with a graphene coating not only prevents oxidation of the silver layer but also can improve the silver sensing performance due to the large surface-to-volume ratio of graphene. The dual-core PCF-SPR biosensor is numerically analyzed by the finite-element method (FEM). An average spectral sensitivity of 4350 nm/refractive index unit (RIU) in the sensing range between 1.39 and 1.42 and maximum spectral sensitivity of 10,000 nm/RIU in the sensing range between 1.43 and 1.46 are obtained, corresponding to a high resolution of 1 × 10⁻⁶ RIU as a biosensor. Our analysis shows that the optical spectra of the PCF-SPR biosensor can be optimized by varying the structural parameters of the structure, suggesting promising applications in biological and biochemical detection.

     

A蛋白定向固定抗体用于椭偏光学生物传感器免疫检测

椭偏光学生物传感器是在椭偏光学显微成像技术的基础上发展的一项生物传感技术。它能够直接观测固体表面上的生物分子面密度,毋需任何标记辅助,适合发展成为一种无标记免疫检测技术。研究了在硅片表面上通过A蛋白定向固定抗体分子用于椭偏光学生物传感器免疫检测的可能性。实验结果表明,通过A蛋白固定抗体得到的抗体膜层的均一性和固定量的重复性能够保证椭偏光学生物传感器免疫检测结果的质量。通过A蛋白定向固定的抗体的抗原结合位点趋向一致,显著提高了抗体与抗原结合的能力。此外,通过蛋白A固定的免疫球蛋白G分子能够结合更多的多克隆抗体分子说明通过A蛋白固定的蛋白质分子能够较好地保持其空间构象。     

A label-free optical sensor based on nanoporous gold arrays for the detection of oligodeoxynucleotides

Interest in using nanoporous materials for sensing applications has increased. The present study reports a method of preparing well-ordered nanoporous gold arrays using a porous silicon (PSi) template. Gold nanolayer could be electrodeposited on the surface of the PSi template at low electrolysis currents in low concentration of chloroauric acid (HAuCl₄) solution. Surface morphology characterizations and optical measurements revealed that a PSi-templated nanoporous gold (Au–PSi) array well replicated the nanoporous structure and retained the optical properties of PSi. Fourier transform reflectometric interference spectra showed that a characteristic blue-shifted effective optical thickness (EOT) was observed due to the low refractive index of the gold film. An optical DNA biosensor was then fabricated via the self-assembly of single-stranded DNA (ssDNA) with a specific sequence on the surface of Au–PSi. The attachment of ssDNA and its hybridization with target oligonucleotides (ODNs) persistently caused the blue shift of the EOT. Consequently, a relationship between the EOT shift and the ODN concentration was established. The mechanism of the optical response caused by DNA hybridization on the Au–PSi surface was qualitatively explained by the electromagnetic theory and electrochemical impedance spectroscopy (EIS). The lowest detection limit for target ODNs was estimated at around 10⁻¹⁴ mol L⁻¹, when the baseline noise, a variation in the value of EOT is around 5 nm. The fabricated Au–PSi based optical biosensor has potential use in the discovery of new ODN drugs because it will be able to detect the binding event between ODNs and the target DNA.     

Whole blood optical biosensor

The future of rapid point-of-care diagnostics depends on the development of cheap, noncomplex, and easily integrated systems to analyze biological samples directly from the patient (e.g. blood, urine, and saliva). A key concern in diagnostic biosensing is signal differentiation between non-specifically bound material and the specific capture of target molecules. This is a particular challenge for optical detection devices in analyzing complex biological samples. Here we demonstrate a porous silicon (PSi) label-free optical biosensor that has intrinsic size-exclusion filtering capabilities which enhances signal differentiation. We present the first demonstration of highly repeatable, specific detection of immunoglobulin G (IgG) in serum and whole blood samples over a typical physiological range using the PSi material as both a biosensor substrate and filter.     

Optical microsensors for pesticides identification based on porous silicon technology

A simple and low cost optical sensor, based on porous silicon nanotechnology, has been used to detect and quantify the presence of atrazine pesticide in water and humic acid solutions. In both cases, a well defined optical signal variation can be registered, even at low concentration as 1 ppm. The phenomenon can be ascribed to the capillary infiltration of liquid into the pores, which changes the average refractive index of the structure. Due to the resonant cavity enhanced operation of the proposed sensors, very low detection limits can be reached.     

Improving the Sensitivity of Fiber Surface Plasmon Resonance Sensor by Filling Liquid in a Hollow Core Photonic Crystal Fiber

Inspired by the classic theory, we suggest that the performance of a D-shaped fiber optical surface plasmon resonance (SPR) sensor can be improved by manipulating the fiber core mode. To demonstrate this, we propose a novel fiber SPR sensor based on a hollow core photonic crystal fiber with liquid mixture filled in the core. The fiber sensor design involves a side-polished fiber with gold film deposited on the polished plane and liquid filling. Numerical simulation results suggest that by tuning the refractive index of the liquid mixture, the predicted sensitivity will be over 6,430 nm/refractive index unit for an aqueous environment, which is competitive for fiber chemical sensing. This optimization method may lead to an ultrahigh sensitivityfiber optical biosensor.     

Application of an interferometric biosensor chip to biomonitoring an endocrine discruptor

RecombinantE. coli ACV 1003 (recA::lacZ) releasing β-galactosidase by a SOS regulon system, when exposed to DNA-damaging compounds, have been used to effectively monitor endocrine disruptors. Low enzyme activity of less than 10 units/mL, corresponding to a μg/L (ppb) range of an endocrine disruptor (tributyl tin, bisphenol A,etc.), can be rapidly determined, not by a conventional time-consuming and tedious enzyme assay, but by an alternative interferometric biosensor. Heavily boron-doped porous silicon for application as an interferometer, was fabricated by etching to form a Fabry-Perot fringe pattern, which caused a change in the refractive index of the medium including β-galactosidase. In order to enhance the immobilization of the porous silicon surface, a calyx crown derivative (ProLinker A) was applied, instead of a conventional biomolecular affinity method using biotin. This resulted in a denser linked formation. The change in the effective optical thickness versus β-galactosidase activity, showed a linear increase up to a concentration of 150 unit β-galactosidase/mL, unlike the sigmoidal increase pattern observed with the biotin.     

Porous silicon-based optical microsensor for the detection of L-glutamine

The molecular binding between the glutamine-binding protein (GlnBP) from Escherichia coli and L-glutamine (Gln) is optically transduced by means of a biosensor based on porous silicon nano-technology. The sensor operates by the measurement of the interferometric fringes in the reflectivity spectrum of a porous silicon Fabry-Perot layer. The binding event is revealed as a shift in wavelength of the fringes. Due to the hydrophobic interaction with the Si-H terminated surface of the porous silicon, the GlnBP protein, which acts as a molecular probe for Gln, penetrates and links into the pores of the porous silicon matrix. We can thus avoid any preliminary functionalization process of the porous layer surface, which is also prevented from oxidation, at least for few cycles of wet measurements. The binding of Gln to GlnBP has also been investigated at different concentration of GlnBP.     

Long Range Surface Plasmons for Observation of Biomolecular Binding Events at Metallic Surfaces

A long range surface plasmon (LRSP) is an electromagnetic wave propagating along a thin metal film with an order of magnitude lower damping than conventional surface plasmon (SP) waves. Thus, the excitation of LRSP is associated with a narrower resonance and it provides larger enhancement of intensity of the electromagnetic field. In surface plasmon resonance (SPR) biosensors, these features allow a more precise observation of the binding of biomolecules in the proximity to the metal surface by using the (label-free) measurement of refractive index (RI) variations and by SP-enhanced fluorescence spectroscopy. In this contribution, we investigate LRSPs excited on a layer structure consisting of a fluoropolymer buffer layer, a thin gold film, and an aqueous sample. By implementing such structure in an SPR sensor, we achieved a 2.4- and 4.4-fold improvement of the resolution in the label-free and fluorescence-based detection, respectively, of the binding of biomolecules in the close proximity to the surface. Moreover, we demonstrate that the sensor resolution can be improved by a factor of 14 and 12 for the label-free and fluorescence-based detection, respectively, if the biomolecular binding events occur within the whole evanescent field of LRSP.     

Application of a Plasmonic Biosensor for Detection of Human Blood Groups

A recently published plasmonic biosensor based on birefringent solid-core microstructured optical fiber is applied for the detection of human blood groups. The birefringent behavior is obtained by removing five central air holes of a two-ring hexagonal lattice of holes in a gold-covered silica fiber with the blood layer surrounding the fiber. The sensing performance of two resonant modes (I based on a phase matching point and II based on a loss matching point) are analyzed. For an increase of the refractive index from 1.3768 (human blood group A) to 1.3796 (human blood group O), the resonance spectral width δλ _0.5 is decreased from 26.8 to 25.8 nm for the core mode I and δλ _0.5 is increased from 28.3 to 33.2 nm for the core mode II. In addition, the amplitude sensitivity S _A is increased from 329.7 to 372.2 RIU^?1 for the core mode I and S _A is decreased from 298.2 to 283.7 RIU^?1 for the core mode II. The average value (26.20 nm for core mode I and 31.07 nm for core mode II) of δλ _0.5 from the human blood groups A, B, and O for our plasmonic biosensor is smaller in comparison with a recently published average value (39.10 nm) of the full width at half maximum (FWHM). Our biosensor can be calibrated for a glycerol-water solution by using the linear dependence between the refractive index n _a and the mass fraction w of the solutes.     

Optical properties of porphyrin molecules immobilized in nano-porous silicon

The paper aims at studying optical properties of porous silicon powders and thin films which were impregnated with different porphyrin molecules. It has been shown that introducing porphyrins into porous silicon matrix results in quenching of luminescence from porous silicon, while luminescence of porphyrins survives, though its structure changes. At the same time, porphyrins in porous silicon matrix which was preliminarily oxidized does not alter luminescence from porphyrins. Generation of singlet oxygen by illuminated porphyrin/porous silicon composite is confirmed by additional oxidation of porous silicon and by the observation of characteristic 1270 nm luminescence band.