This PDF file contains the front matter associated with SPIE Proceedings Volume 11258, including the title page, copyright information, table of contents, and author and conference committee lists.

Detection of biomarkers at low concentrations is essential for early diagnosis of numerous diseases. In many sensitive assays, the target molecules are tagged using fluorescently labeled probes and captured using magnetic beads. Current devices rely on quantifying the target molecules by detecting the fluorescent signal from individual beads. Here, we propose a compact fluorescence-based magnetically aggregated biosensors (MAB) system. Using the device to detect human Interleukin-8, we demonstrated a 0.1 ng/L limit of detection and a 4-log dynamic range, performance which is on par with the most sensitive devices, but is achieved without their bulk and cost.

To make transformative leaps in human health and wellness, our approach to healthcare must be reimagined. Researchers are pursuing multiple avenues, such as integrating health monitoring systems into wearable devices and leveraging machine learning methods to analyze health data. However, many of these approaches are pursued in isolation, and the resulting data is not cross correlated. By working directly with clinicians and clinician-researchers as well as bioinformaticians, we are identifying and addressing their critical needs. This presentation will discuss a recently developed instrument for measuring the elasticity of living tissue. Inspired by conventional mechanical compression testing, the portable instrument replaces the conventional pressure sensor with an array of optical fiber polarimetric sensors to improve both the resolution and sensitivity. These improvements allow the mechanical properties of unprocessed, living, resected tissue to be analyzed. To date, animal tissue samples (several organ systems and cartilage) have been measured. As a result of the improvement in resolution, micron-scale mechanical deformation behavior has been detected, in agreement with the tissue architecture. More complex investigations into the biomechanical properties of tumors (patient derived xenographs) are ongoing as well as improvements in the system design to accelerate data collection and analysis.

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.

Accurate measurement of Amyloid-β biomarkers in blood serum has been highly sought after for early detection of Alzheimer’s Disease (AD). However, non-specific binding and low levels of Amyloid-β in blood pose a problem for traditional immunoassays. Here, we propose a lipid-functionalized biosensor for real-time, label-free detection of Amyloid-β by interaction with whispering gallery modes (WGM) of a microtoroid optical resonator. Non-specific binding is reduced by uniform surface coverage of the lipid, and protein-lipid interactions enhance the shift in resonance frequency. The lipid surface functionalization scheme enables increased accuracy and sensitivity of Amyloid-β and potential for blood-based screening of AD.

Monitoring and controlling processes in industry, healthcare and environment encourage the demand and development of ultrasensitive sensors to detect physical and chemical analytes with very low concentrations. Optical methods based on resonant microstructures, that present high sensitivity, precision, selectivity, sensor lifetime and unit cost, are one of the most promising detection techniques. A fundamental limitation of optical microresonators is the realization of a reliable packaging approach that includes their readout element, e.g., tapered fibers. In this paper, the sensing response of packaged glass bottle microresonators have been demonstrated. Bottle-shaped structures support optical modes called whispering gallery modes along their curvature profile having a quality factor of 2.6 10⁶ at 1550 nm in air. Two simple and robust packages fabricated by 3D printing and glass structuring methods were proposed for temperature and refractive index experiments. A temperature sensitivity of 9.9 pm/K in the range from 17.1°C to 22.5°C was obtained with a taper-coupled bottle system assembled into a plastic package. A similar value has been found when a bottle structure was mounted on a thermally-stable glass base and subjected to temperature changes from 18.6°C to 26.3°C. Both values were theoretically corroborated. For refractive index measurements, the fiber taper has been partially encapsulated employing a low refractive index glue. This provides a free-vibration package solution. Preliminary results shows a refractive index sensitivity of 13 nm/RIU under a constant temperature of 22°C. The proposed fiber-coupled bottle package enables new possibilities for the development of practical sensors.

Ring resonators fabricated in silicon or silicon nitride constitute one of the most versatile and widely studied platform photonic technologies for biosensing. As part of an effort by AIM Photonics to advance the photonics manufacturing infrastructure of the United States, we have designed, fabricated, and tested a series of silicon nitride ring resonators for biosensing. Optimized designs will be incorporated into the AIM Photonics photonic design kit (PDK) and made available to the broader community. This talk will describe the evolution of our designs and their performance, with a particular focus on the detection of cytokines under microfluidic flow.

In this research we present a novel configuration allowing to perform high precision sensing of various vital bio-signs obtained from a fiber-based sensor performing the measurements in a non-tight contact with the skin of the measured subject. We will discuss usage of various types of fibers: single as well as multi-mode. Laser beam is injected into the fiber. In the case of a single mode fiber along the fiber, special artifacts that are breaking the total internal reflection condition, are inserted. Those artifacts are causing to some portion of the injected light to escape the fiber and to interact with the nearby surrounding of the fiber, realizing a smart photonic drip. Changes in the resulted interferencebased intensity at the output of the fiber-sensor is analyzed and associated with various bio-medical signs. In the case of a multi-mode fiber, a detector analyzes the temporal-spatial changes of the 2-D speckle pattern imaged at the tip of the fiber. In both cases the fiber strain, temperature change and vibration associated movements occurring in the proximity of the fiber or in the fiber itself, cause change of the fiber propagating photons phase, polarization and amplitude which leads to temporal-spatial changes in the analyzed speckle pattern or in the resulted interference based intensity measured at the output of the fiber-sensor. After applying proper artificial intelligence (AI) algorithmic, one may correlate those small changes with various vital bio-signs such as heart rate, heart rate variability (HRV), heart sound (phono-cardiogram), respiration rate and sound and even blood pressure.

Understanding the kinetics and dynamics of single enzymes is crucial for understanding biomolecular processes at a fundamental level. Sensors that provide sensitivity to single enzyme conformational changes at micro/nanoseconds time resolution are required to study these motions. Here, we present an optical sensor based on plasmonically enhanced whispering gallery modes capable of studying the dynamics of single enzymes over timescales of ns-hours. By combing surface chemistry methods for attachment of single enzymes in a preferred orientation with lock-in measurement techniques, we detect signals from single enzyme-substrate interactions in the microsecond timescale. Specific immobilization of enzymes on gold nanoparticles is achieved via histidine groups added to one of the termini of the enzyme. This enables reversible attachment of recombinantly expressed and purified enzymes. The molecular motions of the enzyme and its interactions with the substrate is measured as a shift in the whispering gallery mode resonance frequency. A Pound-Drever-Hall lock is used to track the resonance shift with a microsecond time resolution. Combined with advanced signal processing and simulations, this will enable studying the functional conformational movements of enzymes at the single-molecule level. Future work includes adding microfluidics for fast and automated sample delivery, addition of multiple channels of excitation by combing different wavelengths and polarizations of light. This work provides a proof-of-concept next generation optical sensor for single-molecule enzymology, fundamental protein research, drug discovery and point-of-care devices.

We propose to develop a Vernier effect digital sensor from three fiber Bragg gratings. A sensing head in the form of a single mode tapered fiber is placed in one of the cavity. We show, via simulations, that our digital sensor has the detection limit of 3 × 10^-6 RIU which is almost three times of what was previously proposed with cascaded ring resonators.

We present a novel active fiber cavity platform for biosensing applications at 1550nm. We employed the phase shift-cavity ring down spectroscopy to the amplified fiber cavity and demonstrate sensing of sugar solutions with sensitivity and detection limit of 2659o/RIU and 1.11 × 10^-5 RIU, respectively.

Morphological parameters of biological nanoparticles (BNPs) have strong implications on their fate and functionality in vivo e.g., circulation, biodistribution, and clearance. Although interferometric scattering microscopy modalities have demonstrated the label-free detection of sub-100 nm BNPs including viruses and exosomes; they have an insufficient spatial resolution roughly limited to the illumination wavelength. Here, we introduce computational imaging to interferometric scattering microscopy with asymmetric illumination and demonstrate a two-fold resolution enhancement. We demonstrate high-resolution imaging of nanoparticles across a large field-of-view of 100 µm × 100 µm. This novel imaging platform enables ultrasensitive and label-free morphological visualization of low-index sub-diffraction-limited BNPs in a high-throughput manner at subwavelength resolution.

We describe a biosensing module in which live bacteria, genetically “tailored” to respond to the presence of a specific target material, constitute the core sensing element, reporting their response by bioluminescence. The module is constructed of two channels: an ‘induced’ channel that measures the bioluminescent light emitted by bacteria exposed to the inspected area, and a ‘reference’ channel that measures in parallel the bioluminescent light emitted spontaneously by bacteria of the same batch. This enables to overcome signal variations generated by different batches of bacteria, and due to varying environmental operating conditions. A special low-noise optoelectronic circuit was constructed to detect the bioluminescence emitted by the bacteria in both channels. The bacteria are encapsulated in polymer beads that also contain nutrients and water, enabling long-term maintenance-free operation. The beads are packaged in special cassettes at the bottom of the module, so that the induced channel cassette is in direct contact with the ground underneath the module, whereas the reference channel cassette is isolated from the ground. The module contains, in addition, a digital signal processing unit, and a wireless communication unit. The module is designed to operate outdoors as an autonomous network element designed for large scale in-situ deployment. The module described herein was developed for the detection of buried landmines, by sensing the presence of 2,4-dinitrotoluene (DNT) vapors released by the mine, accumulating in the ground above it. Detection of DNT in the sub-ppm range is demonstrated.

A lot of individuals residing in resource limited settings where timely access to medical care is a challenge and healthcare infrastructure is usually poor have no access to laboratory facilities. Disease diagnosis in such sites is dependent on the presence of point-of-care (POC) devices. These POC diagnostics play a key role in ensuring rapid patient care because they are simple to use, inexpensive, portable, instrument independent and do not require a trained technician to operate. In this study, we used a smartphone camera as a spectrometer for measurement of rhodamine at different concentrations. Rhodamine was used as the analyte of choice for proof of concept purposes. The smartphone platform was able to detect the absorption within the visible spectral range from 400 to 700 nm. The results obtained showed that the performance of the smartphone based platform correlates with the conventional microplate reader. From this study, we therefore envision an inexpensive and portable smartphone based devise with connectivity to the internet for POC diagnostics in resource limited settings.

Deep learning is a class of machine learning techniques that uses multi-layered artificial neural networks for automated analysis of signals or data. The name comes from the general structure of deep neural networks, which consist of several layers of artificial neurons, each performing a nonlinear operation, stacked over each other. Beyond its main stream applications such as the recognition and labeling of specific features in images, deep learning holds numerous opportunities for revolutionizing image formation, reconstruction and sensing fields. In this presentation, I will provide an overview of some of our recent work on the use of deep neural networks in advancing computational microscopy and sensing systems, also covering their biomedical applications.

We report the use of a peptide-based capture agent as an alternative to antibodies and nucleic acid-based bioreceptors for porous silicon biosensors. Click chemistry is employed to attach azide-functionalized streptavidin-binding peptides to alkyne-modified porous silicon films. The attachment of the streptavidin-binding peptide and subsequent detection of streptavidin molecules are verified using optical reflectance and Fourier transform infrared spectroscopy measurements.

Biological macromolecules such as antibodies, enzymes, proteins and aptamers have good molecular recognition ability which makes them good candidates for biosensing applications. In this study, glass substrates were treated with silane in order to immobilize HIV gp41 antibodies on their surfaces. The HIV pseudovirus was added to the treated substrates followed by addition of antibodies conjugated to nanoparticles. The surfaces were characterised by using water contact angle, atomic force microscopy (AFM) and Raman spectroscopy. Our preliminary data displayed that the antibodies were indeed immobilized on the glass substrates which made it possible for capturing the intact HIV pseudovirus. Further, Raman spectroscopy revealed the presence of disulphide bonds indicating successful conjugation of the HIV gp41 antibodies to the HIV pseudovirus.