Proceedings Volume 10895

Frontiers in Biological Detection: From Nanosensors to Systems XI

cover
Proceedings Volume 10895

Frontiers in Biological Detection: From Nanosensors to Systems XI

Purchase the printed version of this volume at proceedings.com or access the digital version at SPIE Digital Library.

Volume Details

Date Published: 7 June 2019
Contents: 11 Sessions, 19 Papers, 16 Presentations
Conference: SPIE BiOS 2019
Volume Number: 10895

Table of Contents

icon_mobile_dropdown

Table of Contents

All links to SPIE Proceedings will open in the SPIE Digital Library. external link icon
View Session icon_mobile_dropdown
  • Front Matter: Volume 10895
  • Gratings and Interferometers
  • Photonic Crystals
  • Magnetics
  • Plasmonics
  • Advanced Sensing Methods I
  • Light, Sound, Heat
  • Photonics I
  • Photonics II
  • Advanced Sensing Methods II
  • Poster Session
Front Matter: Volume 10895
icon_mobile_dropdown
Front Matter: Volume 10895
The PDF file contains the front matter associated with SPIE Proceedings Volume 10895, including the Title Page, Copyright information, Table of Contents, and Author and Conference Committee lists.
Gratings and Interferometers
icon_mobile_dropdown
Layer-by-layer nano-assembly of charged polyelectrolytes for label-free optical biosensing with nanostructured materials: the case of nanostructured porous silicon interferometers
S. Mariani, V. Robbiano, L. M. Strambini, et al.
The nano-assembly of charged polyelectrolytes via layer-by-layer (LbL) technology on porous silicon (PSi) interferometers is here demonstrated as an effective biofunctionalization approach for high-sensitivity/selectivity labelfree optical biosensing, using streptavidin/biotin affinity detection as case study. Nanostructured PSi interferometers are biofunctionalized with a nano-assembly of a positively-charged polyelectrolyte, namely, PAH (poly(allylamine hydrochloride)), and a negatively-charged biotinylated polyelectrolyte, namely, b-PMAA (poly(methacrylic acid)), via LbL technology. The nano-assembly is stable under operating conditions and enables the selective and sensitive detection of streptavidin with a sub-picomolar detection limit (namely, DL=0.6 pM), which is 105-fold lower than that achieved with PSi interferometers biofunctionalized using standard silane chemistry. Remarkably, the analytical performance achieved for LbL-biofunctionalized PSi interferometers is comparable to those of state-of-the-art label-free photonic and plasmonic platforms.
Rapid diagnostic susceptibility testing of bacteria and fungi from clinical samples using silicon gratings
Heidi Leonard, Christopher Heuer, Daniel Weizman, et al.
Bacterial and fungal infections persistently plague society and have amounted to one of the most prevalent issues in healthcare today. Thus, significant research effort is directed towards developing rapid diagnostic techniques for determination of the correct antibiotic (or antifungal) for a patient-tailored therapy. We have developed a rapid phenotypic antimicrobial susceptibility testing (AST) in which photonic 2D silicon microarrays are employed as both the optical transducer element and as a preferable solid−liquid interface for bacterial/fungal colonization. We harness the intrinsic ability of the micro-architectures to relay optical phase-shift reflectometric interference spectroscopic measurements (termed PRISM) and incorporate it into a platform for culture-free, label-free tracking of bacterial/fungal colonization, proliferation, and death. For example, bacteria proliferation within the microtopologies results in an increase in refractive index of the medium, yielding an increase in optical path difference, while cell death or bacteriostatic activity results in decreasing or unchanged values. The optical responses of bacteria, including clinical isolates and samples derived from patients at neighboring hospitals, to various concentrations of relevant antibiotics are tracked in real time, allowing for accurate determination of the minimum inhibitory concentration (MIC) values within 2-3 hours in comparison to assay times of <8 hours (using standard broth microdilution techniques or state-of-the-art clinical automated systems. This has opened the door to the observation of unique bacterial behaviors, as we can evaluate bacterial adhesion, growth, and antibiotic resistance on different micro-architectures, different surface chemistries, and even different strains. Motility, charge, and biofilm abilities have been explored for their effect of bacterial adhesion to the microstructures as we further develop our method of rapid, label-free AST for full clinical application.
Photonic Crystals
icon_mobile_dropdown
Towards an all-fiber system for detection and monitoring of ammonia
Detection of ammonia based on an all-fiber configuration is reported. The system consists of a hollowcore photonic-bandgap (HC-PBG) fiber with 20μm core diameter and transmission window from 1490 to 1680 nm. Absorption bands of ammonia at ~1538 nm are targeted using a supercontinuum source with central wavelength at 1550 nm. We present the method of achieving a complete fiber system while addressing the gas entry/exit path through the HC-PBG. Analysis of the ammonia absorbance in the fiber with respect to fiber length and response time is investigated. By operating in the near infrared, we demonstrate how the proposed system addresses several challenges associated with fiber-based gas-sensing, using readily available commercial components.
Label-free and fluorescence photonic crystal biochips for early cancer biomarker detection
We report on the development of a biosensing platform that combines label-free and fluorescence based detection on disposable Bloch surface wave biochips. This system is applied to the detection of the HER2-neu/ErbB2 clinical biomarker related to breast cancer development. We first describe the design and fabrication of the BSW biochips as well as the principle of operation of the optical reading instrument. Then, the approaches for surface functionalization and immobilization of proteins for specific detection on the biochips are discussed. Finally, experimental results on a sandwich immunoassay for ErbB2 detection in cell lysates are presented.
Magnetics
icon_mobile_dropdown
Portable optical diagnostics for early malaria detection
Andrea Armani, Dongyu Chen, Samantha McBirney, et al.
Malaria remains a significant global health problem with nearly half of the world’s population living in malaria-endemic regions and more than 500,000 deaths from malaria and its complications each year. Although significant success has been achieved in malaria therapeutic development, accurate early-stage diagnosis of the disease remains a barrier to eradication, especially in low-resource areas. Optical microscopy and antibody-based diagnostic tests are commonly used for identifying the infected population. However, the cost and reliability of these methods in low-resource environments limit the efficacy and accuracy of malaria screening. In this work, we designed, built, and validated a portable optical diagnostic system for malaria detection. The system is based on the detection of Hemozoin, which is a magnetic nanoparticle byproduct of the parasite. Therefore, the presence of Hemozoin is indicative of malarial infection. Unlike all other naturally occurring materials in the blood, hemozoin is paramagnetic. This property is the foundation of our magneto-optic detection system. In our experiments, β-hematin (a mimic for hemozoin) is used to allow for the verification of our device without the need to handle malaria-infected samples. The system is optimized and tested with spherical iron oxide magnetic nanoparticles and β-hematin in different concentrations of PEG solutions. Finally, β-hematin in whole rabbit blood is detected with this system. Detection limits of <8.1 ng/mL (corresponding to <26 parasites/μL) in 500μL of blood are demonstrated. The threshold for early stage malaria infection is 100 parasites/μL. Therefore, the present system is easily able to detect within a clinically relevant range.
Improving the sensitivity of fluorescence-based immunoassays by photobleaching the autofluorescence of magnetic beads
Shira Roth, Orr Hadass, Meir Cohen, et al.
One of the most common capture surfaces is a magnetic bead. However, magnetic beads exhibit strong autofluorescence, which often overlaps with the emission of the reporter fluorescent dyes and limits the analytical sensitivity of the assay. Here, we photobleached several widely used magnetic beads and reduced their autofluorescence to 1% of the initial value. The photobleached beads were stable over time and their surface functionality was retained. In a high sensitivity LX-200™ system using photobleached magnetic beads, human interleukin-8 was detected with a 3-fold improvement in analytical sensitivity and signal to noise ratio over results achievable with non-bleached beads.
Plasmonics
icon_mobile_dropdown
Rapid and multiplexed detection of Lyme disease using a grating coupled-fluorescent plasmonics (GC-FP) biosensor platform
Eunice Chou, Arturo Pilar, Ernest F Guignon, et al.
Infection with the spirochete Borrelia burgdorferi leads to Lyme disease (LD), the most prevalent tick-borne illness in the Northern Hemisphere. If left untreated, the infection spreads throughout the body, causing multisystem disease. The current standard for LD diagnosis is a two-tiered approach (ELISA followed by Western blot), which targets the immune response to bacterial proteins. This approach, however, lacks sensitivity and specificity, leading to misdiagnosis. We developed a protein microarray assay to detect antibodies against B. burgdorferi proteins with high sensitivity using grating-coupled surface plasmon resonance, combined with fluorescence imaging (Grating Coupled-Fluorescent Plasmonics, GC-FP). Here, we use GC-FP for rapid and multiplexed detection of antibodies from B. burgdorferi in human serum. We confirmed the fluorescence enhancement capability of GC-FP analysis and optimized reagent concentrations for detection of serum antibodies present in human LD. By conducting GC-FP analysis of patient serum samples, we were able to accurately diagnose LD in patients with disseminated and early-stage infection. Our results show that GC-FP can detect IgG antibodies in highly dilute human sera (up to 1:1250X serum dilution) and we are currently establishing whether or not our GC-FP platform can detect serum antibodies with greater sensitivity and specificity compared to the standard Western blot approach. Altogether, our work provides a potential path towards replacement of the cumbersome two-tiered testing algorithm, and thus a streamlined approach to LD diagnosis.
Dark mode plasmonic cavity biosensor (Conference Presentation)
Local field enhancement of plasmonic nanoantennas below the diffraction limit plays an important role in a variety of applications, including surface-enhanced Raman scattering, spontaneous emission enhancement, nanolasing, enhanced nonlinear effects and biosensing. Yet due to the radiation and ohmic loss of these nanocavities, their quality factor (Q) is much smaller than a typical optical microcavity Q factor, such as that of a microsphere or microtoroid. Coupling a nanoantenna to an optical microcavity increases the Q of the hybrid plasmonic-photonic system, however, this dramatically degrades the Q of the original microcavity. Here, we propose a judicious hybridization of a plasmonic dark mode of a gold nanoring and whispering gallery mode (WGM) of a microtoroid. It is shown through finite element simulation that the hybridized WGM and dark mode of the proposed plasmonic gold nanoring solves the aforementioned issues in two ways. First, the small radiation loss of the dark mode minimizes Q degradation and allows the system to maintain its ultra-high Q. Second, the nanoring enhances the field on the microcavity’s surface which in turn increases the interaction between, for example, a biomolecular target and the WGM. We have shown that the proposed system generates larger resonance shifts compared to a microcavity loaded with same volume of conventional linear gold nanoantennas . This results in significant enhancement in the system’s sensitivity. We have repeated the same simulations for different materials and volumes.
Identification of body fluids using metal enhanced fluorescence substrate with glancing angle deposited Ag nanorods (Conference Presentation)
Naseem Abbas, Xun Lu, Mohsin ali Badshah, et al.
The identification of body fluids including blood, saliva, urine, sweat, semen, and vaginal fluid can be a vital evidence that can be used to identify a suspect and reconstructing the criminal case. Since the amount of evidence in the crime site is limited, a multiplex identification system for body fluid using a small amount of sample is prepared. In this research, we proposed a multiplex detection platform for semen and vaginal fluid, which were important for sexual crime using an Ag vertical nanorod metal enhanced fluorescence (Ag-MEF) substrate. The Ag-MEF substrate with a length of 500 nm was fabricated by glancing angle deposition and the Amin functionalization was conducted to improve the binding ability. The effect of incubation time was analyzed and an incubation time of 60 min was selected where the fluorescence signal was saturated. To examine the performance of the developed identification chip, an identification of the semen and virginal fluid was carried out. The developed sensor can selectively identify the semen and virginal fluid without any cross reaction. In addition, the limit of detection for semen was 10 times lower than that of the commercially available RSID-Semen kit.
Nanoplasmonic discrimination of organic solvents using a bimetallic optical tongue
Justin R. Sperling, Gerard Macias, Glenn A. Burley, et al.
Optical sensor arrays serve as excellent tools for the recognition and discrimination of a variety of liquid and gas mixtures. They achieve this via pattern-based recognition from signals across multiple sensing regions, where each region is modified to produce a different interaction, such as partial-selectivity, with desired analytes. As their use progresses towards rapid, highly personalized diagnosis and component identification devices, reduction in complexity and data-acquisition time is key. One way to achieve this is through reducing the number of elements in the array without compromising the differential capabilities of the device. Here, we present a device with elements consisting of plasmonic sensors of two superimposed plasmonic nanoarrays; one fabricated using gold and the other aluminum. Each material produces a distinct plasmonic response while also allowing us to selectively functionalize each pattern with a different ‘sensing chemistry.’ This allows for the development of different partially-selective elements, via modification with functional thiols and silanes, respectively. Since optical sensing arrays of this type require multiple sensing regions, each producing a different optical response, our bimetallic method results in twice as much data from one measurement, providing the same amount of data necessary to allow for successful differentiation with fewer elements in the sensing array. We demonstrate that by altering the surface chemistry of the nanostructures we can tune their partial selectivity to organic solvents. We believe this technology could be useful in areas that rely on assays for simultaneous determination of multiple analytes, such as the medical, food and drug, and security industries.
Advanced Sensing Methods I
icon_mobile_dropdown
Double emulsion optofluidic microlasers
Han Zhang, Chen Zhang, Yuze Sun
Double emulsion droplets have found diverse applications in biosensing, chemical synthesis, drug delivery, and highthroughput screening and production. In this work, we demonstrate monodisperse double emulsion optofluidic microlasers with a dye-doped thin shell structure. In particular, robust generation of water-in-oil-in-water (W/O/W) double emulsion droplets in a hydrodynamic flow focusing microfluidic device is demonstrated. With careful arrangement of the three liquid components in the double emulsion, an optical microcavity is formed which supports the whispering gallery modes (WGMs) that locate near the surface of the shell layer. Low-threshold lasing has been achieved in W/O/W double emulsion droplets. Lasing emission from double emulsion droplets with different diameter and different shell layer thickness are characterized on the flow. Due to the high degree of control provided by the microfluidic device, both droplet size and shell layer thickness can be conveniently tuned, and thus the lasing properties. The unique two-phase core-shell structure of the double emulsion droplets provides great flexibility and potential in the development of biosensing platform based on the optofluidic laser system demonstrated in this work, especially in the high-throughput bioanalysis.
Fluorescence imaging immuno-assay biosensors on biological photonic crystals (Conference Presentation)
Kenneth Squire, Paul LeDuff, Gregory L. Rorrer, et al.
Optical biosensing has achieved remarkable levels of sensitivity and has enabled early detection of various toxins and biomarkers. Fluorescence spectroscopy is among the most common and powerful optical detection techniques, capable of single molecule detection. This is done by exciting the sample using a light source, collecting the fluorescence light inherent in the sample or on a reporter molecule, and measuring the fluorescence spectrum using a spectrometer. This modality is effective for multiplex sensing as full spectral data is acquired. However, fluorescence spectroscopy requires multiple measurements at multiple points to achieve a representative sampling of a sensor. Fluorescence imaging is a detection modality similar to fluorescence spectroscopy, but replaces the spectrometer with an imager such as a camera thus reducing cost and complexity. Imaging allows data acquisition at multiple points in a large area of your sensor in a single measurement making it a more efficient sensing method but does not acquire spectral data. Both fluorescence sensing modalities have been shown to be very powerful in pristine laboratory settings but when the equipment or measurement area are not ideal, additional enhancement is needed. This can be achieved by implementing a sensing substrate capable of enhancing fluorescence signals to practical detection levels. Diatoms are unicellular marine organisms that grow a biosilica shell called a frustule. These frustules are porous with nanostructured patterns and represent naturally occurring photonic crystals which are known to enhance excitation and emission of fluorophores. In addition to the optical enhancements of diatoms, the large surface area allows for large numbers of analytes to aggregate making fluorescence signals stronger. In this work, we employ naturally occurring photonic crystal diatoms to create a sensor capable of enhancing the fluorescence of a standard sandwich immunoassay. Using this sensor, we achieved detection down to 10-16 M using fluorescence spectroscopy and 10-15 M for fluorescence imaging. These represent a 100× and 10× enhancement for the two respective detection modalities over equivalent, non-diatom sensors. This highlights the capability of our sensor to enhance fluorescence optical signals and its potential to be used in point-of-care biosensing applications.
X-ray readout for implanted medical sensors (Conference Presentation)
Passive chemical and mechanical sensors were developed with readout via X-ray projection imaging (plain radiography). Physicians routinely use X-rays to image anatomy and associated pathologies because they penetrate through deep tissue and show contrast between air, soft tissue, bone, and metal hardware. However, X-rays are usually blind to local biochemical information (e.g., pH) and insensitive to small biomechanical changes (e.g., in mechanical strain and pressure). Such information is critical for studying, detecting, and monitoring pathologies associated with implanted medical hardware, such as fracture non-union and implant-associated infection. We developed sensors attached to implanted medical devices to augment plain radiographs with chemical or mechanical signals shown on a radiopaque dial. For example, a polyacrylic acid-based hydrogel with pH-dependent swelling was attached to an orthopedic plate; the local pH was then determined by measuring the position of a radiopaque tungsten indicator pin embedded within the hydrogel. The pH sensor was calibrated in standard pH buffers and tested during bacterial growth in culture. Its response was negligibly affected by changes in temperature and ionic strength within the normal physiological range. Radiographic measurements were also performed in cadaveric tissue with the sensor attached to an implanted orthopedic plate fixed to a tibia. Pin position readings varied by 100 µm between observers surveying the same radiographs, corresponding to 0.065 pH unit precision in the range pH 4-8. We have also developed mechanical pin and hydraulic fluid-level sensor to amplify and display mechanical strain/bending of orthopedic implants for monitoring bone fracture healing.
Light, Sound, Heat
icon_mobile_dropdown
Speckle based sensing of chemicals by an acoustic excitation in aqueous solutions
Hadar Genish, Nisan Ozana, Zeev Zalevsky
The optical activity of glucose in aqueous solutions offers a very high specificity in detecting the presence of glucose. In this presentation we will present several concepts for non-invasive detection of glucose, being realized in-vitro as well as in-vivo. In all cases the sensing concept is based upon analysis of time changing spatial statistics of back scattered speckle patterns when being analyzed by properly defocused optics. We will focus on an experimental approach in which we try to employ contactless measurement of acoustic excitations in solutions containing various chemical while using analysis of those time changing speckle pattern. Solutions containing glucose should response differently than those where glucose is absent. To perform this measurement, we excited acoustic waves in a solution and measured the changes in the speckle pattern. The basic concept is that while the solution is acoustically excited the acoustic waves modulate the density of the fluid under examination. This modulation will have two effects on the speckle pattern, the first is a spatial and time-varying modulation of the effective refractive index, and the second is a spatial and time-varying modulation of the optical rotation which is induced by the presence of glucose. Both of these effects should change the speckle pattern, which if recorded with an exposure time which is longer than the acoustic period, will be seen as a smearing of the pattern. By analyzing properties such as speckle size, contrast and/or correlation between images, it is possible to extract a signal which is proportional to the amplitude of the acoustic excitation.
Monitoring of ammonia in an aqueous environment using a supercontinuum-based photoacoustic sensing system
We demonstrate a robust photoacoustic medium for measuring the concentration of ammonia in an aqueous solution. We target the near-infrared (NIR) overtone absorption band (~1540 nm) of ammonia with a supercontinuum (SC) laser-based excitation system and an immersion-based acoustic transducer as the detection system. We further present how such a simple system can be used to perform effective in-situ measurements of ammonia over a range of concentrations with a sensitivity of parts per million (ppm) by volume and linearity of <96%. We demonstrate how the sensing system can be readily tailored to monitor the concentrations of other miscible gases in the aqueous solution.
High-throughput droplet-based microfluidic optical calorimeter
Michael I. Recht, Jacob Chamoun, Ashish Pattekar, et al.
Calorimetry is a powerful label-free technique for characterizing biochemical interactions. However, conventional calorimeters are limited by large sample requirements and low throughput, relegating their use to a limited number of high-value measurements. To increase the throughput and sensitivity of calorimetry, we have developed a novel microfluidic calorimeter that uses optical methods to measure the temperature change caused by reactions occurring in sub-nanoliter droplets. In this calorimeter, a microfluidic system creates a mixed droplet of reactants, a thermochromic liquid crystal (TLC) reporter converts the temperature change to a spectral shift, and a sensitive optical detector measures the spectral shift. Experimental measurements of the temperature change induced in droplets by the exothermic binding of EDTA to Ca2+ show good agreement with a thermal multiphysics model. Our ongoing work to improve the microfluidic mixing of reactants and increase the temperature resolution of the calorimeter has yielded a temperature resolution for this calorimeter of 2.4 mK, which corresponds to an energy resolution of 16 nJ. This resolution is on the same order as commercial isothermal titration calorimeter (ITC) systems and 10-fold better than most nanocalorimeters.
Photonics I
icon_mobile_dropdown
Packaged microbubble resonators as a robust field sensing device
Abraham J. Qavi, Jie Liao, Royce Dong, et al.
Whispering Gallery Mode (WGM) microresonators are a powerful class of optical devices in which light is confined within a small volume. These devices offer the advantages of high sensitivity, affordable cost of fabrication, and ease of integration with conventional electronic systems. In particular, microbubble resonators are a unique type of WGM devices in which the optical and fluidic elements are combined into a single component. We have developed a packaged, silica microbubble resonator device for field applications using 3-D printed substrates. These devices offer Qfactors at high as 106.
Pedestaled subwavelength grating metamaterial waveguide for sensitivity enhancement (Conference Presentation)
Ching-Wen Chang, Xiaochuan Xu, Swapnajit Chakravarty, et al.
Silicon photonics has been studied intensively for biosensing applications due to the potential of leveraging the matured fabrication process to integrate thousands of sensors on a single chip and massively produce sensing chips at an affordable cost. However, the high index contrast of silicon does not only enable ultra-compact sensors, but also limits the interaction between optical field and analytes. To enhance the sensitivity, silicon subwavelength grating metamaterial (SGM) microring resonator was proposed to improve the interaction between photons and analytes and has demonstrated significant sensitivity improvement. Due to the asymmetric index profile along the vertical direction, further increasing the sensitivity becomes challenging. To reduce the asymmetricity, in this paper, we propose pedestaled SGM which allows further increasing the interaction between optical field and analytes. We analyzed and demonstrated enhanced bulk sensitivity and limit of detection (LOD) in SGM microring resonators with pedestal structure. To compare the bulk sensitivity and LOD of regular SGM microring resonator (Sample A) and pedestal SGM microring resonators, the devices with same structure design as Sample A were soaked in buffered oxide etch (BOE) for 30 seconds (Sample B) and 50 seconds (Sample C) to make pedestal shape. Real time monitoring of the resonance shift measurement shows the detection of streptavidin at a low concentration of 0.1 ng/mL for Sample C and a similar response for 1 ng/mL, 10 ng/mL, 100 ng/mL, 1 μg/mL, 10 μg/mL, and 100 μg/mL. Our results suggest that such pedestaled SGM microring resonators have great potential for specific biomarkers diagnosis.
Photonics II
icon_mobile_dropdown
A multiplexed platform for point of care diagnostics based on optical waveguide technology (Conference Presentation)
Optical waveguides are proving to be an optimal platform for on-the-spot biosensors. Optical signal transduction provides high discrimination, where even a single fluorescent molecule can be detected. The use of evanescent wave illumination, where the light field extends a fraction of the wavelength above a sensor surface, provides a clean signal for surface reactions with minimal background. By only illuminating a volume extending above the surface by a few hundred nanometers, evanescent wave sensors often don’t require wash steps or other sample processing complexities. The cost of optical technology has been reduced considerably over the past decade with the explosion of digital imaging. All of these factors combine to make for a very practical biosensor design. We will present the architecture and design features of the MBio Diagnostics LightDeck® evanescent planar waveguide sensor, and two of the applications where these practical features enable commercial devices: testing for antibiotic residues in milk, and tests to manage sepsis. Antibiotic residue testing in milk products is widely performed and requires prompt results on-site at a dairy processor. The cost constraints are quite severe. We detail the approach using waveguide sensors, and present data on residue testing. In a second application, sepsis presents a complex disease state that requires a number of results in real time. With multiple biomarkers, and often algorithmic approaches to analysis, a multiplex platform is essential to delivering the necessary data on-the-spot. We detail host response biomarker panels with applications in risk stratification and therapy optimization.
Development of silicon nitride photonic microring resonator arrays as a biosensing platform for multiplex detection of biologically relevant protein targets (Conference Presentation)
Michael Bryan, Benjamin L. Miller
There is considerable interest in the development of photonic-based biosensing technologies to enable low-cost point-of-care detection and diagnostics. Ring resonator arrays have emerged as a promising format to realize multiplexed assays for biologically relevant protein targets. Much of the published work on ring resonator-based biosensors utilize traditional telecommunications laser sources between the O and L bands, where silicon and silicon dioxide are transparent, but absorption by an aqueous cladding is relatively high. We hypothesized that ring resonator-based biosensors designed to operate near a “notch” in the absorption spectrum of water would yield superior performance characteristics. To that end, we have designed ring resonators in silicon nitride to operate with an 840 nm wavelength laser source. These designs were fabricated at the American Institute for Manufacturing Integrated Photonics (AIM Photonics) foundry. Here we report our progress designing, characterizing, and demonstrating these devices in the application of multiplex assays for biologically relevant protein targets.
Cost-effective optical biosensing using integrated photonics (Conference Presentation)
Cost-effective Point-of-Care (POC) diagnostics are of considerable interest to modern healthcare. Current POC devices are typically disposable, low-complexity, and qualitative, with quantitation only achievable at significant additional cost. Clinical diagnostic tools in centralized labs provide better quantitation, but are cumbersome, time-inefficient, expensive, and require trained operators. We hypothesized that Si3N4 and SU-8 photoresist ring resonators would allow for quantitative and inexpensive sensing of clinically relevant serum biomarkers. To test this hypothesis, we designed silicon nitride-based ring resonators that were then fabricated at the American Institute for Manufacturing Integrated Photonics (AIM Photonics). We also designed SU-8 polymer ring resonators, and fabricated those using in-house facilities. Single mode waveguides were designed for transverse electric and transverse magnetic polarizations at λ=1550 nm using COMSOL Multiphysics® and PhoeniX OptoDesigner. Devices were addressed by end-fire coupling and characterized by assessing spectral features including quality factor, finesse, and free spectral range. Bulk solution refractive index sensitivity was achieved using sucrose solutions. Specific interaction was shown by spiking C-Reactive Protein (CRP), an indicator of inflammatory response, into fetal bovine serum and identifying concentration dependent wavelength shift. This discussion will focus on device design, characterization, and the ability of silicon photonics to sense clinically relevant biomolecules in the label-free regime.
Long-range surface plasmon waveguide biosensors for disease detection
We review long-range surface plasmon-polariton waveguide biosensors and their application to disease detection in complex fluids. The biosensors are constructed from metal stripe waveguides cladded in Cytop with etched microfluidic channels to expose the stripe surface to the sensing fluid. Application of waveguide biosensors to the detection of leukemia in patient blood serum and dengue infection in patient blood plasma is reviewed. In addition, a novel bioassay for HIV detection in complex fluids is proposed and preliminary results are demonstrated. The biosensors are compact and mass manufacturable using semiconductor fabrication tools and processes.
Advanced Sensing Methods II
icon_mobile_dropdown
A fast and reproducible ELISA laser platform
Xiaotian Tan, Qiushu Chen, Hongbo Zhu, et al.
Optofluidic bio-lasers are currently of high interest for sensitive, intra-cavity, biochemical analysis. In comparison with conventional methods such as fluorescence and colorimetric detection, lasers provide us with a method for amplifying small concentration differences in the gain medium, thus achieving high sensitivity. Our previous research has demonstrated that sandwich IL-6 ELISA performed in capillary-based optofluidic laser cavity was able to achieve ultrahigh detection sensitivity (LOD between 1-10 fg/ml) with a small sample volume (~20 μL). However, such approach has several limitations such as low repeatability and long assay time (~8 hours in total, 7 hours for laser measurements). Here, we developed a novel on-chip ELISA laser platform by directly fabricating micro-wells on dielectric mirrors for immunosorbent reactions. Polystyrene microbeads of 30 μm in diameter were placed in the wells to optically enhance the resonance cavity during laser measurement, thus significantly improving reliability, shortening assay time (~1.5 hours, 30 minutes for laser measurements) while maintaining the attractive features such as small sample volume and very high sensitivity (LOD ~0.1 pg/mL for IL-6). This work pushes the ELISA laser one step closer to solving problems in realworld biochemical analysis.
Poster Session
icon_mobile_dropdown
Direct laser writing of optical biosensor based on photonic Floquet topological insulator for protein detection
Photonic Floquet topological insulators (PFTI) allow scatter-free propagation of light along its edges. The PFTI of interest consists of helical waveguides arranged in a honeycomb lattice. When irradiated with an input beam on the edge of the PFTI, light propagates from one end of the waveguide-system to the other along the edges. The intensity and the final position of light is theoretically found to be dependent on the difference in the refractive indices of the core and cladding of the waveguides. For a system of helical-waveguides filled with a solvent, the effective refractive index of the system varies with the concentration of the analyte in the solvent and this can be measured by monitoring the position and intensity of the output-light. This paper discusses the design, principle, simulation and fabrication of such a PFTI based biosensor.
Design and FDTD simulation of photonic crystal based sensor for biosensing applications
Sello Manoto, Chemist Mabena, Rudzani Malabi, et al.
Photonic crystals (PhCs) is a unique and flexible class of optical devices that are able to manipulate the electromagnetic fields of light. PhCs is a subwavelength grating structure with a periodic arrangement of a high refractive index layer coated on a low refractive index material and can provide a strong light confinement depending on the size, periodicity and the refractive index. Finite difference time domain (FDTD) method can be used to simulate the electromagnetic properties of light through complex structures such as PhCs, because of the precision of the method in the description of geometry and properties of the material. In this study, FDTD software from Lumerical was used to design and simulate the electromagnetic properties of the PhCs based sensor for biosensing applications. The transmission, reflection and absorption characteristics through the proposed PhCs structure was analysed using a visible wavelength range of 400- 700 nm. The boundary conditions were correctly chosen and consisted of periodic boundary conditions and perfectly matched layers. The results revealed that the transmission and reflectance were dependent on the period of the PhCs and the enhanced electric field was confined in an area allowing for interaction with biological analytes.
Bio-inspired visual sensing enhances imaging techniques using integrated electro-optical switchable filters
Marquise N. Pullen, Adam K. Fontecchio
Traditional imaging systems are modeled after human vision, a static trichromatic vision, sensitive to visible light alone. However, in nature not all biological agents have the same visual/spectral constraints as humans; some can see ultraviolet, others visible, others infrared, and some a mixture. The design of the traditional imaging system only accounts for a small subset of the vision systems found in nature. Such limitations imposed by an imaging system limits the research of biological agents that see differently than humans. Different biological visual data is critical for having a complete understanding of the world, under ever-changing environmental conditions. To address the limitations of traditional imaging systems, a conceptualized design using electrooptical switchable filters to mimic the vision of biological agents, scalable to the varying number of color vision systems (e.g. dichromatic, trichromatic, etc.) found in nature and capable of demonstrating the physiological changes a biological vision system can experience has been developed. Electro-optical switchable filters have two optical modes, one for spectral transmission and another for spectral reflections; these two modes are used to model a biological agents color recognition or blindness abilities.