Lyme disease, the most common tick-borne illness in the United States, is a significant clinical diagnostic challenge. The current approach is standard or modified two-tiered tests (STTT/MTTT), which both offer limited accuracy. A biosensing platform with nanoscale plasmonic gratings to enhance signal from antibodies was developed to resolve these issues. Human serum samples with known Lyme disease status were tested on the biosensor. These samples included patients in early and late stages of the disease, as well as healthy controls. The results were analyzed with ROC analysis to determine diagnostic thresholds. Scoring the data with these thresholds showed improved accuracy over STTT and MTTT. Further machine learning analysis on the data yielded similar results to the ROC analysis.. Based on these results, this biosensor has the potential to improve clinical outcomes for Lyme disease by enabling earlier disease diagnosis through higher sensitivity toward early stages of Lyme disease.
Beyond the optical and analytical performance of the sensor itself, the development of an optical detection tool in response to a pressing research or diagnostic need requires consideration of a host of additional factors. This talk will provide an overview of two photonic sensor systems developed for profiling the human immune response to COVID-19 infection and/or vaccination. One, focused on the design goal of high multiplexing (many targets per sensor), was built on the Arrayed Imaging Reflectometry (AIR) platform. AIR is a free-space optics technique that relies on the creation and target molecule binding-induced disruption of an antireflective coating on the surface of a silicon chip. The second method, focused on low cost and high speed, uses a small (1 x 4 mm) ring resonator photonic chip embedded in a plastic card able to provide passive transport of human samples. This “disposable photonics” platform is able to detect and quantify anti-COVID antibodies in a human sample in a minute, making it attractive for high-throughput testing applications.
Detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. The urgent need for antibody detection tools has proven particularly acute in the COVID-19 era. Array-based tools are desirable as methods for assessing broader patterns of antigen-specific responses, as well as providing information on SARS-CoV-2 immunity in the context of pre-existing immunity to other viruses. Also, methods that rapidly and quantitatively detect antibody responses to SARS-CoV-2 antigens using small (fingerstick) quantities of blood are essential for monitoring immunity at a global scale. This talk will describe the development of two optical sensor platforms (Arrayed Imaging Reflectometry, and an integrated photonics platform fabricated at AIM Photonics) for quantifying antibodies to SARS-CoV-2 and other upper respiratory pathogens, and oriented towards the needs of multiplex detection and speed.
Continual development of optical testing methodologies for silicon photonic components and circuitry is instrumental for the overall growth of the field. A mature scheme capable of coupling light between the fiber core and single mode silicon-on-insulator (SOI) waveguides for wafer-scale testing are grating couplers. When silicon photonics are integrated into 3D architectures, the photonics layer may undergo multiple wafer flipping steps through bond/de-bond modules. Architectures such as this require optical testing on the front and backside of the wafer. Conventional grating couplers integrate reflective layers or additional layers of gratings to increase coupling efficiency. These techniques however will not work in both wafer orientations. In addition, including separate test structures for both front and backside fabrication increases device footprint and drives up manufacturing costs. We present an isotropic grating coupler that provides moderate coupling efficiency for both front and backside wafer-scale testing. The grating coupler has been designed for use in the AIM Photonics multi project wafer (MPW) platform, thus enabling non-contact optical interfacing irrespective of the wafer orientation. We have numerically demonstrated coupling efficiencies of 34% (-4.7dB) and 28% (-5.5 dB) for the wafer front and backside respectively while operating at a wavelength of 1550 nm. With proof of concept established, we foresee an eventual pathway for achieving higher efficiency isotropic grating couplers traversing into more 3D silicon photonic architectures.
As scaling becomes more challenging, new approaches to transistor design, new materials, and new devices are all being explored. Advanced transistor designs such as vertically stacked nanowire and nanosheet FETs (NW/NS FETs) provide a pathway to sub-10 nm devices. Ferroelectric High κ enables extension of FinFET and NW/NS FETs as well as providing a potential dielectric for memristive devices, including RRAM and ferroelectric tunnel junctions. NW/NS FETs provide a significant challenge for both processing and process control due to the geometries associated with their 3D structure. Increasing computational power will ultimately require more than scaling, however. Neuromorphic (brain like) computing and non-Von Neumann computing architectures are now being explored as alternative options for increasing computation capability. To develop efficient neuromorphic and non-Von Neumann hardware, new devices and materials integration strategies are required. This paper provides an overview of advanced NW/NS transistors and new memristor devices and materials and their characterization and metrology.
Detection of antibodies in the blood is an important clinical technique for diagnosing active infections and previous exposures. The grating-coupled fluorescent plasmonics (GC-FP) biosensing platform has been used to detect Lyme disease serum antibodies in patients and has been shown to be more sensitive than the current standard tests. In this study, we sought to design an affordable GC-FP detection system without sacrificing the sensitivity of data output. We further optimized our analysis strategies to achieve highly sensitive and consistent diagnostic results. This work ultimately aims to fill an unmet need for better detection of human Lyme disease.
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.
Infection with the spirochete Borrelia burgdorferi leads to Lyme disease, the most common tick-borne disease in North America, Europe, and Asia. Currently, Lyme disease is diagnosed using a two-tiered approach of ELISA/immunofluorescence, followed by Western blot analysis. These assays measure serological immune response to the infection, namely levels of IgG or IgM antibodies that bind to B. burgdorferi antigens. However, the existing approach is non-quantitative, lacks sensitivity, and may contribute to delayed diagnosis. In this study, grating-coupled fluorescence plasmonics (GC-FP) was used for rapid, highly-multiplexed detection of antibodies that bind B. burgdorferi proteins in human and mouse blood serum. GC-FP is an optical plasmonic method that enables quantitative detection of molecular interactions and can be incorporated into microfluidic format for highly multiplexed testing. We have demonstrated that this technique allows us to use only three microliters of blood serum to quantitatively detect multiple target antibodies within 30 minutes. We have also shown that GC-FP is faster and more sensitive than the traditional two-tiered Lyme disease testing scheme, making it attractive for diagnostic purposes. This proof-of-concept study provides foundations to develop GC-FP as a highly sensitive diagnostic tool to enhance the efficiency of assessment for Lyme disease patients, which will ultimately improve treatment outcomes.
Nanotechnology has recently been applied to a wide range of biological systems. In particular, there is a current push to
examine the interface between the biological world and micro/nano-scale systems. Our research in this field has led to
the development of novel strategies for spatial patterning of biomolecules, electrical and optical biosensing,
nanomaterial delivery systems, single-cell manipulation, and the study of cellular interactions with nano-structured
surfaces. Current work on these topics will be presented, including work on novel, semiconductor-based DNA detection
methods and mechanical, atomic force microscopy (AFM)-based characterization of bacterial biofilms in threedimensional
microfluidic systems.
Microfluidic devices are currently being utilized in many types of BioMEMS and medical applications. In
these systems, the interaction between the surface and the biological specimen depends critically on surface properties.
The surface roughness and chemistry as well as the surface area to which the biomolecules or cells are exposed affect
this interaction. Modification of the surface of microfluidic channels can improve the operation of the device by
influencing the behavior of the biological specimens that are flowing through it. SU-8 is an epoxy-based, negative
photoresist that has been previously used to create covered channels. Once cured, it is both chemically and thermally
stable. It is also optically transparent above 360 nm, which allows optical measurements, including fluorescence
imaging, to be taken inside the channel. SU-8 microchannels have been fabricated with a porous layer on the sidewalls
by the photo-lithographic process, which is reproducible with precisely controlled channel dimensions. In order to attain
these porous sidewalls, no additional fabrication steps are required outside the standard photo-lithographic process. The
porosity of the sidewalls is a result of incomplete cross-linking of the polymer. The obtained porous surfaces can be
specially treated to provide conditions preferable for biological interactions. The porous layer increases the internal
surface area available on the sidewalls, which make these microfluidic channels preferable for biological applications.
This paper describes the details of the fabrication process and the experiments that verify the benefit of using SU-8
microchannels with porous sidewalls.
Cancerous tumors are dynamic microenvironments that require unique analytical tools for their study. Better
understanding of tumor microenvironments may reveal mechanisms behind tumor progression and generate new strategies for diagnostic marker development, which can be used routinely in histopathological analysis. Previous studies have shown that cell invasion and intravasation are related to metastatic potential and have linked these activities to gene expression patterns seen in migratory and invasive tumor cells in vivo. Existing analytical methods for tumor microenvironments include collection of tumor cells through a catheter needle loaded with a chemical or protein attractant (chemoattractant). This method has some limitations and restrictions, including time constraints of cell collection, long term anesthetization, and in vivo imaging inside the catheter. In this study, a novel implantable device was designed to replace the catheter-based method. The 1.5mm x 0.5mm x 0.24mm device is designed to controllably release chemoattractants for stimulation of tumor cell migration and subsequent cell capture. Devices were fabricated using standard microfabrication techniques and have been shown to mediate controlled release of bovine serum albumin (BSA) and epidermal growth factor (EGF). Optically transparent indium tin oxide (ITO) electrodes have been incorporated into the device for impedance-based measurement of cell density and have been shown to be compatible with in vivo multi-photon imaging of cell migration.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.