Microcavity structures have recently found utility in chemical/biological sensing applications. The appeal of these structures over other refractive index-based sensing schemes, such as those based on surface plasmon resonance, lies in their potential for producing a highly sensitive response to binding events. High-Q devices, characterized by sharp line widths, are extremely attractive for sensing applications because the bound analyte provides an increased optical pathlength, thus shifting the resonant frequency of the device. In this work, we design and simulate resonant microrings using full-wave finite element models. In addition to structure design, integration of the biological recognition element on the resonator is also considered. This is equally important in dictating the sensitivity of the sensing device. To this end, we take a four-step theoretical approach to optimizing the sensor. We begin by using FEM analysis to obtain the characteristic resonant wavelength, line width, and quality factor for bare ring resonators absent of surface functionalization. Next, we simulate the structure with a biorecognition element attached to the surface. The third step is to model the functionalized microring to mimic the interaction with the target analyte. At each step, we derive the transmission spectra, electric field distributions and coupling efficiencies, as well as wavelength dependence using empirical data for the refractive indices of biorecognition element and analyte. Finally, the geometry of the microrings is optimized in conjunction with the constituent material properties and the recognition chemistry using FEM combined with an optimization algorithm to maximize the sensitivity of the integrated biosensor.

The progress in bioanalytics caused a growing demand of innovation in reliable, miniaturized and low cost optical sensor systems based on integrated optical devices. We present a detailed analysis of sensor elements for applications in aqueous solution based on two cascaded microring resonators (MRRs) by using the Vernier effect (VE). This approach is beneficial for ultra-high sensitivity at large fabrication tolerances, aspects of crucial importance for the practical detection of biomolecules such as peptides. The architecture consists of two silicon nitride microrings connected via a bus waveguide. The free spectral range (FSR) of individual rings is slightly different in order to achieve VE. Thereby the external refractive index of the reference ring is fixed; the second one varies due to the presence of the analyte. The precise operation is controlled by using spectral tuning via integrated micro-heaters. Theoretical analysis has been performed for different structural parameters. A sensitivity several orders of magnitude higher than in the case of a single ring can be predicted for TE and TM polarization, respectively. The first design of Vernier devices and its experimental characterization will be presented. The devices include tapered grating couplers in order to couple light between fibers and chip at moderate alignment tolerances in a reliable manner. Therefore, by combining the VE and the spectral tuning, cascaded MRRs are an optical configuration very promising for sensing applications.

A grating coupled porous silicon (pSi) Bloch Surface Wave (BSW) biosensor capable of supporting a surface mode is demonstrated for the real-time detection of both small and large molecules. In contrast to most pSi based sensor platforms that are unable to perform high sensitivity detection of large molecules that do not infiltrate into the porous matrix, the pSi BSW sensor has more than 15% of the field intensity confined to the surface of the structure, allowing for high sensitivity detection of surface-bound large molecules. Angular interrogated reflectance measurements were carried out to benchmark the performance of the pSi BSW against two common pSi sensor platforms, the waveguide and microcavity, after exposing each sensor to two different small molecules and one large molecule in a flow-cell environment. All of the sensors showed comparable sensitivity towards the detection of the small molecules, but the BSW sensor was clearly superior for detection of the large molecules. The experimental results were found to be in good agreement with simulations based on rigorous coupled wave analysis and the transfer matrix method.

Detection of biomolecules on microarrays based on label-free on-chip optical biosensors is very attractive since this format avoids complex chemistries caused by steric hindrance of labels. Application areas include the detection of cancers and allergens, and food-borne pathogens to name a few. We have demonstrated photonic crystal microcavity biosensors with high sensitivity down to 1pM concentrations (67pg/ml). High sensitivities were achieved by slow light engineering which reduced the radiation loss and increased the stored energy in the photonic crystal microcavity resonance mode. Resonances with high quality factor Q~26,760 in liquid ambient, coupled with larger optical mode volumes allowed enhanced interaction with the analyte biomolecules which resulted in sensitivities down to 10 cells per micro-liter to lung cancer cell lysates. The specificity of detection was ensured by multiplexed detections from multiple photonic crystal microcavities arrayed on the arms of a multimode interference power splitter. Specific binding interactions and control experiments were performed simultaneously at the same instant of time with the same 60 microliter sample volume. Specificity is further ensured by sandwich assay methods in the multiplexed experiment. Sandwich assay based amplification increased the sensitivity further resulting in the detection of lung cancer cell lysates down to concentrations of 2 cells per micro-liter. The miniaturization enabled by photonic crystal biosensors coupled with waveguide interconnected layout thus offers the potential of high throughput proteomics with high sensitivity and specificity.

We experimentally demonstrate optical trapping of single B. subtilis spores using the enhanced field of a cavity at resonance in a planar silicon photonic crystal. By tracking the suppressed Brownian motion of a spore in three types of optical traps, generated with three types of cavities (H0, H1 and L3) we derive trap stiffnesses of around 7.6 pN/nm/W and find good agreement with calculated values obtained with 3D FDTD simulations. We envision that planar photonic crystals provide a suitable platform for the manipulation and sensing of bio-particles.

Resonant optical microcavites of two-dimensional photonic crystals (2D PhC) are responsive to refractive index changes in the immediate vicinity and thus provide a label-free platform for sensing biological molecules. Because their active sensing volume is ~ 1 μm³, exceptionally sensitive detection of biomolecules is, in principle, achievable from complex biological samples. Previously, we have demonstrated detection of human-IgG protein and virus-like particles by measuring changes in the optical transmission spectrum from the 2D PhC after it has been treated with analyte and dried. However, this drying step restricts practical utility of the platform especially in the case of clinical diagnostics wherein multiple samples need to be tested in short duration. In our progress toward this, we have demonstrated successful integration of microfluidic channels with the 2D PhC device and we further characterized the temperature and bulk refractive index sensitivity of the device.

We experimentally demonstrated a silicon photonic crystal (PC) microcavity biosensor with 50 femto-molar detection limit. Our devices have demonstrated sensitivities higher than than competing optical platforms at concentration of 0.1μg/ml across a range of dissociation constants KD 1 micro-molar to 1 femto-molar. High sensitivities were achieved by slow light engineering which reduced the radiation loss and increased the stored energy in the PC microcavity resonance mode which contributed to high Q as well as enhanced optical mode overlap with the analyte. By integrating subwavelength grating coupler, we showed that not only coupling efficiency increased but also the working device yield significantly improved

Chemical gradients drive many processes in biology, ranging from nerve signal transduction to ovulation. At present, microscopy is the primary tool used to understand these gradients. Microscopy has provided many important breakthroughs in our understanding of the fundamental biology, but is limited due to the need to incorporate fluorescent molecules into a biological system. As a result, there is a need to develop tools that can measure chemical gradient formation in biological systems that do not require fluorescent modification of the molecules in question, can be multiplexed to measure more than one molecule and is compatible with a variety of biological sample types, including in vitro cell cultures and ex vivo tissue slices. Work from our group centered on the development of microscale tools to measure chemical gradients will be presented. In this project, we have developed a microfluidic interface that allows for sampling from underneath a tissue slice or in vitro cell culture system. The sampling system can resolve up to 19 different ports and can be interfaced with either electrochemical or fluorescence-based detection methods. Using these two detection methods, we are capable of analyzing the release of either small molecule metabolites or proteins and peptides using immunoassays.

According to the CDC, breast cancer is the most common cancer and the second leading cause of cancer related deaths among women. Metastasis, or the presence of secondary tumors caused by the spread of cancer cells via the circulatory or lymphatic systems, significantly worsens the prognosis of any breast cancer patient. In this study, a technique is developed to detect circulating breast cancer cells in human blood using a photoacoustic flow cytometry method. A Q-switched laser with a 5 ns pulse at 532 nm is used to interrogate thousands of cells with one pulse as they flow through the beam path. Cells which are pigmented, either naturally or artificially, emit an ultrasound wave as a result of the photoacoustic (PA) effect. Breast cancer cells are targeted with chromophores through immunochemistry in order to provide pigment. After which, the device is calibrated to demonstrate a single-cell detection limit. Cultured breast cancer cells are added to whole blood to reach a biologically relevant concentration of about 25-45 breast cancer cells per 1 mL of blood. An in vitro photoacoustic flow cytometer is used to detect and isolate these cells followed by capture with the use of a micromanipulator. This method can not only be used to determine the disease state of the patient and the response to therapy, it can also be used for genetic testing and in vitro drug trials since the circulating cell can be captured and studied.

The objective of the present work is to determine the opportunities and challenges for Biophotonics business development in Europe for the next five years with a focus on sensors and systems: for health diagnostics and monitoring; for air, water and food safety and quality control. The development of this roadmap was initiated and supported by EPIC (The European Photonics Industry Consortium). We summarize the final roadmap data: market application segments and trends, analysis of the market access criteria, analysis of the technology trends and major bottlenecks and challenges per application.

The BioPhotonics community is buzzing at the prospect that ulta-small bio-nanoparticles such as Polio virus and protein can be detected label-free in their native state and sized one at a time. As the awareness that the claim of label-free single protein sensing through the frequency shift of a bare microcavity by A.M. Armani et al in Science in 2007 fades from lack of independent experimental confirmation or a viable physical mechanism to account for the magnitude of the reported wavelength shifts, a new approach has captured the community’s interest. It is a product of a marriage between nano-optics and micro-photonics, and is poised to take label-free sensing to the limit.

A capillary microresonator platform for label-free refractometric sensing is demonstrated by coating the interior of thick-walled silica capillaries with a sub-wavelength layer of high refractive index, dye-doped polymer. No intermediate processing, such as etching or tapering, of the capillary is required. Side illumination and detection of the polymer layer reveals a fluorescence spectrum that is periodically modulated by the presence of whispering gallery modes within the layer. The fabricated capillary resonators exhibited sensitivities to changes in internal refractive index of up to 29.44 nm/RIU, demonstrated by flowing through aqueous dilutions of glucose. Thick walled capillaries are used in order to readily allow interfacing with existing biological and chemical sensing and separation platforms such as capillary electrophoresis or gas chromatography where such capillaries are routinely used. The interior polymer coating method described here could enable the use of a wide range of materials for the design of optofluidic label-free sensors integrated with industry standard (bio)chemical analytical separation platforms.

The novel platform presented in this paper is design to answer the unmet challenge of real time label free in-vivo sensing by bringing together a refractive index transducing mechanism based on Whispering Gallery Modes in dye doped microspheres combined with Microstructured Optical Fibers. In addition to providing the provides the remote excitation and collection of the WGM signal, the fibre also allows easily manipulation of the microresonator and the use this sensor in a dip sensing architecture, alleviating the need for a complex microfluidic interface. Here, we demonstrate the ability of this sensing platform to be operated above its lasing threshold, enabling enhanced performance.

This study focuses on the design, fabrication and characterization of a tapered optical fiber platform for the label-free detection of aqueous and gaseous biomolecules. Single mode fibers were tapered to a diameter of approximately 10 microns, and this tapered surface was functionalized with biomolecules for aqueous (antibody) detection of analytes. Molecular binding to the surface changes the refractive index and thickness of the biolayer, which interacts with propagating light, causing a measureable phase shift in the output.

In this research, hybrid hydrogels of poly (vinyl alcohol)/ porous silicon (PSi)/theophylline were synthesized by the freezing and thawing method. We evaluated the influence of the synthesis parameters of the poly (vinyl alcohol) (PVA) hydrogels in relation to their ability to swell and drug released. The parameters studied (using an experimental design developed in Minitab 16) were the polymer concentration, the freezing temperature and the number of freezing/thawing (f/t) cycles. Nanostructured porous silicon particles (NsPSi) and theophylline were added within the polymer matrix to increase the drug charge and the polymer mechanical strength. The hybrid hydrogels were characterized by Infrared Spectroscopy Fourier Transform (FTIR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Differential Scanning Calorimetry (DSC), drug delivery kinetics were engineered according to the desired drug release schedule.

When metallic nanoparticles are put in the vicinity of semiconductor quantum dots and driven by a coherent light source, their intrinsic plasmonic fields can be replaced with a new type of fields (coherent-plasmonic fields). These fields are generated via coherent coupling of excitons in quantum dots and localized surface plasmon resonances (LSPRs). We show the coherent-plasmonic field of a metallic nanoparticle can lead to a significantly larger field enhancement than that caused by its LSPR. Utilizing this, we investigate how such a coherent field enhancement can improve the sensitivities plasmonic nanosensors for detection single biological molecules. The results demonstrate application of quantum coherence in quantum dot-metallic nanoparticle systems for chemical and biological sensing applications.

We initiate a fundamental study of modal-plasmonic interactions in nanostructured resonance elements with the aim to develop new hybrid multiparametric sensors. The proposed hybrid sensor operates under guided-mode resonance (GMR) and surface-plasmon resonance (SPR) in unison. Numerical simulations of gold-integrated periodic resonant films show effective spectral conversions due to interplay between these mechanisms. In some cases, we find enhancements in sensitivity and attendant reduced resonance linewidths improving sensor resolution. Initial experimental results incorporating modal-plasmonic interactions in a resonant system containing a dielectric grating on a thin gold film agree qualitatively with theory. The research is important as the SPR and GMR concepts are independently the basis for commercial sensor systems with major economic impact.

There is a great need for rapid detection of bio-hazardous species particularly in applications to food safety and biodefense. It has been recently demonstrated that the colonies of various bio-species could be rapidly detected using culture-specific and reproducible patterns generated by scattered non-coherent light. However, the method heavily relies on a digital pattern recognition algorithm, which is rather complex, requires substantial computational power and is prone to ambiguities due to shift, scale, or orientation mismatch between the analyzed pattern and the reference from the library. The improvement could be made, if, in addition to the intensity of the scattered optical wave, its phase would be also simultaneously recorded and used for the digital holographic pattern recognition. In this feasibility study the research team recorded digital Gabor-type (in-line) holograms of colonies of micro-organisms, such as Salmonella with a laser diode as a low-coherence light source and a lensless high-resolution (2.0x2.0 micron pixel pitch) digital image sensor. The colonies were grown in conventional Petri dishes using standard methods. The digitally recorded holograms were used for computational reconstruction of the amplitude and phase information of the optical wave diffracted on the colonies. Besides, the pattern recognition of the colony fragments using the cross-correlation between the digital hologram was also implemented. The colonies of mold fungi Altenaria sp, Rhizophus, sp, and Aspergillus sp have been also generating nano-colloidal silver during their growth in specially prepared matrices. The silver-specific plasmonic optical extinction peak at 410-nm was also used for rapid detection and growth monitoring of the fungi colonies.

The struggle against tuberculosis is one of the World Health Organization priorities. Identifying in a short time, patients with active tuberculosis, would bring a tremendous improvement to the current situation. Recovering from this infectious and deadly disease (2 million of death per year) is possible with a correct diagnosis to give an appropriate treatment. Unfortunately, most common tuberculosis diagnoses have few drawbacks: - skin tests: not reliable at 100% and need an incubation of 2 days before the diagnosis, - blood tests: costly and sophisticated technology, - chest X-ray: the first step before the sputum tests used for a bacterial culture with a final diagnosis given within 2 weeks. A tuberculosis test based on exhaled breath analysis is a prospective and noninvasive solution, cheap and easy to use and to transport. This test lies on a fluoregenic detection of niacin, a well-known mycobacterium tuberculosis specific metabolite. In this paper, it is assumed that the selected probe is specific to niacin and that exhaled breath does not contain any interfering species. To address this problem, a fluorimeter is developed with a cheap and cooled CCD ( 2k$) as a sensor, to easily determine the suitable “fluorescent zone”. In comparing aqueous solutions with and without niacin, 250 pM of niacin have been detected. With a commercial fluorimeter (Fluorolog from Horiba), only 200 nM of niacin are detected. The present detection remains 10 times above the estimated targeted value for a tuberculosis test. The excitation source is a LED, which typically emits 20 W at 265 nm through an optical fiber. The emission signal is detected around 545 nm. A typical light exposure lasts 700 seconds. Analysis of biomarkers with a liquid fluorimeter is generic and promising as health diagnosis.

The properties of micro-porous ceramics are studied in the present work using a tunable diode-laser-based setup. The relative optical porosity is retrieved by using gas in scattering media absorption spectroscopy (GASMAS) – which yields the path length travelled by photons through the gas-filled pores – and frequency domain photon migration (FDPM) – which evaluates the mean optical path length (MOPL) through the whole ceramic. The relationship between the relative optical porosity and the physical porosity is also studied.

Breath analysis is an attractive non-invasive strategy for early disease recognition or diagnosis, and for therapeutic progression monitoring, as quantitative compositional analysis of breath can be related to biomarker panels provided by a specific physiological condition invoked by e.g., pulmonary diseases, lung cancer, breast cancer, and others. As exhaled breath contains comprehensive information on e.g., the metabolic state, and since in particular volatile organic constituents (VOCs) in exhaled breath may be indicative of certain disease states, analytical techniques for advanced breath diagnostics should be capable of sufficient molecular discrimination and quantification of constituents at ppm-ppb - or even lower - concentration levels. While individual analytical techniques such as e.g., mid-infrared spectroscopy may provide access to a range of relevant molecules, some IR-inactive constituents require the combination of IR sensing schemes with orthogonal analytical tools for extended molecular coverage. Combining mid-infrared hollow waveguides (HWGs) with luminescence sensors (LS) appears particularly attractive, as these complementary analytical techniques allow to simultaneously analyze total CO₂ (via luminescence), the ¹²CO₂/¹³CO₂ tracer-to-tracee (TTR) ratio (via IR), selected VOCs (via IR) and O₂ (via luminescence) in exhaled breath, yet, establishing a single diagnostic platform as both sensors simultaneously interact with the same breath sample volume. In the present study, we take advantage of a particularly compact (shoebox-size) FTIR spectrometer combined with novel substrate-integrated hollow waveguide (iHWG) recently developed by our research team, and miniaturized fiberoptic luminescence sensors for establishing a multi-constituent breath analysis tool that is ideally compatible with mouse intensive care stations (MICU). Given the low tidal volume and flow of exhaled mouse breath, the TTR is usually determined after sample collection via gas chromatography coupled to mass spectrometric detection. Here, we aim at potentially continuously analyzing the TTR via iHWGs and LS flow-through sensors requiring only minute (< 1 mL) sample volumes. Furthermore, this study explores non-linearities observed for the calibration functions of ¹²CO₂ and ¹³CO₂ potentially resulting from effects related to optical collision diameters e.g., in presence of molecular oxygen. It is anticipated that the simultaneous continuous analysis of oxygen via LS will facilitate the correction of these effects after inclusion within appropriate multivariate calibration models, thus providing more reliable and robust calibration schemes for continuously monitoring relevant breath constituents.

Several concepts have been developed in the recent years for nanomaterial based integrated MEMS platform in order to accelerate the process of biological sample preparation followed by selective screening and identification of target molecules. In this context, there exist several challenges which need to be addressed in the process of electrical lysis of biological cells. These are due to (i) low resource settings while achieving maximal lysis (ii) high throughput of target molecules to be detected (iii) automated extraction and purification of relevant molecules such as DNA and protein from extremely small volume of sample (iv) requirement of fast, accurate and yet scalable methods (v) multifunctionality toward process monitoring and (vi) downward compatibility with already existing diagnostic protocols. This paper reports on the optimization of electrical lysis process based on various different nanocomposite coated electrodes placed in a microfluidic channel. The nanocomposites are synthesized using different nanomaterials like Zinc nanorod dispersion in polymer. The efficiency of electrical lysis with various different electrode coatings has been experimentally verified in terms of DNA concentration, amplification and protein yield. The influence of the coating thickness on the injection current densities has been analyzed. We further correlate experimentally the current density vs. voltage relationship with the extent of bacterial cell lysis. A coupled multiphysics based simulation model is used to predict the cell trajectories and lysis efficiencies under various electrode boundary conditions as estimated from experimental results. Detailed in-situ fluorescence imaging and spectroscopy studies are performed to validate various hypotheses.

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