This PDF file contains the front matter associated with SPIE Proceedings Volume 11087, including the Title Page, Copyright information, Table of Contents, Author and Conference Committee lists.

Development of simple techniques for detection of nucleic acids is essential for clinical diagnostics. MicroRNA (miRNA) have been identified as potential biomarkers in early detection of various diseases, including esophageal adenocarcinoma (EAC) and Barrett’s esophagus (BE). However, these small molecules have not been adopted into clinical practice because of challenging aspects in the lab. The technology described herein is a label-free nanoprobe referred to as “inverse molecular sentinel” (iMS) for gastrointestinal cancer diagnosis using surface-enhanced Raman scattering (SERS) detection. The results of this study provide evidence supporting the robust iMS method for miRNA sensing without the need for PCR.

Porous silicon nanoparticles (PSiNPs) have attracted increasing interest for imaging and treatment of diseases due to biocompatibility, large specific capacity for drug loading, non-toxic degradation products, and intrinsic photoluminescence (PL). In particular, the PL lifetime is typically on the order of microseconds, significantly longer than the nanosecond lifetimes exhibited by fluorescent molecules naturally presented in cells and tissues, thus allows discrimination of the silicon nanoparticle from the tissue autofluorescence. Herein, the long-lived PL is employed to monitor the status of drug payload elution, associated with biodegradation of the silicon nanocarriers, and demonstrated as a “self-reporting” system. Dissolution of the silicon matrix in physiological environment triggers drug release, along with decreasing intensity and blue shift of the PL spectra. Furthermore, by tracking the PL lifetime, the drug releasing status and the residual lifespan of the silicon nanocarriers are correspondingly acquired. The PL lifetime is a physically intensive property that can report only the inherent characteristics of the PSiNPs regardless of surrounding noise while the intensity-based reporting is substantially affected by many unwanted factors. We investigate a unique means to inform the lifespan of the PSiNPs as a biodegradable drug nanocarrier in vivo. This study presents a promising potential of the photoluminescent PSiNPs toward advanced drug delivery systems for translational medical platform including theranostics and visualized drug delivery tracking.

Silicon nanoparticles represent a new class of imaging agents with emission lifetimes in the 1 to 100 microsecond range. This important timescale--many cellular transport processes, neuronal transmission events, and biochemical reactions occur on microsecond timescales--offers opportunities for silicon nanoparticle probes to be deployed for such imaging problems. Furthermore, when in contact with cellular conditions, the emission spectrum from silicon nanoparticles evolves on a much longer timescale (minutes to days) based on slow oxidation and dissolution of the nanostructure. This presentation will discuss the photophysical properties that enable time-gated and related imaging modalities, and it will discuss chemical modifications that can be deployed to allow porous Si nanoparticles to traffic between the cellular surface (via peptide targeting) and the cell interior (via membrane fusogenic coatings) to improve fidelity of in vitro and in vivo images.

Spatially distributed biosensors are being developed for many healthcare applications. We have focused on such sensor arrays with the longer term goal of developing technologies for reading out and writing in information for brain circuits. In this presentation we highlight recent work where approaches to large scale cortical neural interfaces by entirely wireless means are developed, built as spatially distributed autonomous networks of wireless neural microsensors. From a systems level perspective, three key elements are critical: (i) individual sensor design and fabrication of hermetic, active electronic microdevices; (ii) implementation of high data rate wireless telecommunication methods, scalable for thousands of sensors; (iii) high performance computing platforms to decode and encode large amounts of physiological data for real-time analysis.

We are developing a voltage-sensitive magnetic resonance imaging (MRI) contrast agent capable of detecting neuronal activity deep within the brain, as well as sensing activation in the peripheral nervous system. The contrast agent will allow nervous system activity to be read out by an external device, with spatial resolution of 30 microns and temporal resolution of 10 milliseconds. The field sensitivity appears to be as low as 20 volts/meter, which is several orders of magnitude higher than the sensitivity of optical contrast agents. We have also validated that injection of a similar particle can be used to initiate behavioral changes in mice upon application of an external changing magnetic field. The external field is about 10 mT, which can be produced with a wearable device. We have also validated the ability to magnetically inject particles into the brain (in mice) intra-nasally, with efficiency that is several hundred times higher than non-magnetic inhalation. The combination of these two products will be useful as a neuroscience/neuroengineering imaging tool, a clinical diagnostic tool, and, in the future, as a robust brain-machine interface

The number of people with spinal cord injury living in the United States is currently estimated to be approximately 288,000 persons and about 42,000 are veterans. Spine injuries are more prevalent among Operation Iraqi Freedom and Operation Enduring Freedom veterans than among veterans of prior conflicts due to advances in body armor making injuries more survivable. Today, activity-based therapies are the only medical practices that can be used to enhance recovery after spinal cord injury. Several studies have now shown that spinal cord stimulation delivered at the right time can enhance a physical therapy rehabilitation program significantly, leading to restoration of volitional walking. Here, we will discuss efforts to develop a bi-directional tool for sensing and stimulating the spinal cord in order to bridge a gap ‘reconnect’ patches of eloquent tissue, without the need external systems. Our platform innovates on the use of high-density electrode arrays; the use of state-of-the-art artificial neural network designs, optimization methods, and neural network-accelerated hardware targets; and layout of a device regulatory pathway for fully implanted system for advanced future therapies. Such technological demonstration of a spine-machine-spine interface will be of immediate practical and therapeutic utility to the wounded warrior with SCI. More generally, such technology could be used across other axes of spinal cord injury, including chronic pain and achieve additive therapeutic outcomes.

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.

Point-of-care (POC) diagnostic devices hold great promise to significantly impact healthcare delivery and address health disparities by shifting the focus away from the utilization of high-cost specialized care for the treatment of late-stage diseases toward predictive, preventative, and personalized health for more effective disease monitoring and management. In the developed world, POC technologies are expected to offer effective and feasible means of reducing healthcare costs and improving patient care, whereas in the developing world POC technologies are urgently needed to address pressing healthcare needs with affordable and accessible solutions. In this talk, I will first provide a brief overview of the field of POC technologies for health diagnostics. To showcase an example, I will next present our work on ClotChip, a microfluidic sensor that utilizes dielectric spectroscopy for POC assessment of blood coagulation disorders with <10 uL of whole blood. Specifically, I will analyze a simple circuit model that accurately captures the frequency-dependent dielectric behavior of human whole blood placed within a microfluidic channel. I will then discuss how temporal variation in the dielectric properties of the blood sample undergoing coagulation provides information about molecular and cellular abnormalities in the hemostatic process. Finally, to establish the utility of ClotChip as a platform technology for POC assessment of hemostasis, I will share our results from a pilot clinical study with ClotChip on monitoring anticoagulation therapy with a new class of FDA-approved blood thinners. Results from correlative studies between ClotChip and several existing blood coagulation assays are also provided.

Describing the possibilities that can be achieved using the Myant's proprietary Textile Computing platform that can detect metrics ranging from Biochemistry, Biomechanics, Eletrophysiology and Heamodynamics.

The food industry such as meat producers and plant product processors have tremendous interest in detecting pathogenic organisms such as E.coli, Listeria, and Salmonella in very low concentrations down to a single cell. These pathogenic organisms when they are in the right environment can start multiplying exponentially. For example, E.coli cells can double every 20 minutes posing a tremendous danger for their growth in over many hours. We have designed an optical device that attaches to a smartphone providing an imaging and processing device that achieves an optical resolution of 1 micron. The optics is engineered to reduce aberrations in the system. We also developed a smartphone application that can track microbeads and bacteria in the video frames in real time using computer vision algorithms. We extract individual bacterial image segments in these videos to train neural network models to detect and differentiate different types of bacteria such as E.coli and B.subtilis. These trained models can detect and discriminate E.coli from B.subtilis with high accuracy of more than 80%. This approach has the potential to train different types of bacteria with a multiclass neural network classifier by training them with images from different genera and species of bacteria. Such a classifier can detect them in a wild sample containing many types of bacteria with low-cost smartphone optical device.

The mechanisms by which cells respond to mechanical stimuli are essential for cell function yet not well understood. Many rheological tools have been developed to characterize cellular viscoelastic properties but these typically have limited throughput or require complex schemes. We have developed quantitative phase imaging methods which can image structural changes in cells due to mechanical stimuli at the nanoscale. These methods are label free and can image cells in culture or flowing through microfluidic chips, providing high throughput measurements. We will present our single-shot phase imaging method that measures refractive index variance and relates it to disorder strength, which correlates to measured cellular mechanical properties such as shear modulus. Studies will be presented which relate mechanical properties to early carcinogenic events, investigate the role of specific cellular structural proteins in mechanotransduction and track water regulation due to mechanical stress.

Utilizing radioluminescent properties of materials is one of the oldest methods for ionizing radiation detection and dosimetry. In the context of radiation therapy dosimetry and quality assurance, dosimeters composed of materials with unique radioluminescent characteristics in conjunction with optical fibers have practical advantageous properties including the ability to perform in vivo and intracavitary measurements with high spatial and temporal resolution. In this work, our recent progress toward design and characterization of fiber-based radioluminescent probes for radiation therapy dosimetry using spectroscopic techniques and specialty fiber optics is briefly reviewed.

This paper contains structural and logical scheme of the research; theoretical information about the set of azimuthally invariant Mueller-matrix elements and their combinations; The work is aimed at the development of a set of techniques that form a new method of azimuthally invariant differential polarimetry of partially-depolarizing optically anisotropic biological layers. This method is based on the determination and diagnostic use of a set of physical relationships between the distributions of azimuthally invariant polarization parameters characterizing the optical anisotropy of partially depolarizing layers of biological tissues, and the distributions of the parameters of linear and circular birefringence of such objects.

Presented research materials: • coordinate maps of the degree of depolarization (CMD) of polycrystalline structures of histological sections of parenchymal (spleen) biological tissues of the deceased with different levels of blood loss; • magnitudes and ranges of changes in the statistical moments of the 1st - 4th orders characterizing the distribution of the magnitude of the CMD of biological organs (spleen, kidney) of the deceased with varying degrees of blood loss; • efficiency and accuracy of determining the degree of blood loss of the deceased by the method of diffuse Mueller-matrix polarimetry of polycrystalline structures of histological sections of parenchymal tissues of the deceased with different levels of blood loss.

A model of weak phase fluctuations of polycrystalline films of biological fluids is proposed. A correlation approach has been used to describe the polarization manifestations of the linear and circular birefringence of biological planar polycrystalline networks. Algorithms of polarization experimental measurement of the module (orientation map) and phase (phase map) of a set of "two-point" parameters of the Stokes vector are determined. The sets of orientation and phase maps of polycrystalline films of bile and blood are studied experimentally. The diagnostic possibilities of statistical analysis of the module and phase distributions of the "two-point" parameters of the Stokes vector of polarization-inhomogeneous images are considered. The magnitudes and ranges of changes in the set of statistical moments of the 1st and 4th orders that characterize the orientation and phase maps of polycrystalline films of bile and blood are found. The sensitivity, specificity and balanced accuracy of the method of polarization-correlation mapping in the diagnosis of early stage of cholelithiasis, as well as differentiation of the degree of blood losses, were determined.

The results of the multifunctional Stokes polarimetric mapping of the manifestations of phase and amplitude anisotropy of histological sections of the internal organs of rats are presented. The methods of statistical analysis of vector-parametric images are used. Criteria for the differentiation of pathological conditions are obtained.

The results of multifunctional polarization-phase mapping of histological sections of adenoma and prostate carcinoma are presented. Used methods of statistical and wavelet analysis. The criteria for differentiation of benign and malignant conditions are obtained.

Transition metal dichalcogenides (TMDs) are among the most appealing candidates for sensor applications due to their atomically thin layered structure, dangling bond free surface, and novel physical properties. Recently, TMD materials have been used to improve the performance of devices like metal-oxide semiconductor field-effect transistors (MOSFETs) and tunneling field-effect transistors (TFETs). TMD material based TFETs show a steep subthreshold slope (SS) due to the better gate control on the channel and band-to-band tunneling transport. This makes the TMD TFETs a potential candidate for sensing devices. The steep SS of TFETs and higher gate control is useful for detecting charged biomolecules such as protein and DNA. The presented device shows a SS of 50 mV/decade for 5 decade change in drain current and a sensitivity (ΔI_DS/I_DS) of 2.11 for a 5 mV change in gate voltage. Biomolecules were detected by measuring the variation of the drain current due to bimolecular charge.

Nanoparticle-based fluorescence DNA/RNA sensing offers promising applications in both research and medical diagnosis due to the ease of surface chemical modification and sample handling, allowing detection in complex media. The performance of the conventional fluorescence biosensors is often limited by the insufficient fluorescence signal. To overcome the disadvantage, we advanced silver-coated magnetic nanoparticles with strong plasmon resonance to enhance the molecular beacon (MB)-based nucleic acid nanosensors. The silver-coated magnetic nanoparticles were chemically synthesized to compose of 20 nm iron oxide magnetic nanoparticle core and 60 nm thick Ag coating, forming iron oxide/Ag core-shell nanoparticles. Fluorescently labeled DNA MBs were immobilized on the Ag surface which serves as the quencher for the closed MBs and provides fluorescence enhancement for the unfolded MBs in the presence of the complementary target sequence. More importantly, the improved Ag shell mitigates the strong optical absorbance in the visible range associated with the magnetic nanoparticles increasing the fluorescence intensity. The detection was performed by dispersing the nanosensors in a 20 μl analyte solution for 10 minutes for accelerated target capture through 3D diffusion and concentrating them magnetically for enhanced fluorescence signal acquisition. The rapid, label-free DNA detection resulted in a detection limit of 10 pM target DNA.

We demonstrate a novel optofluidic micropipette device for filter-free fluorescence-based biosensing. The optofluidic micropipette tube composed of a glass capillary microtube and a polymer-based structure designed to load analyte solution using a regular micropipette and serves as an optical waveguide. Ray-tracing simulations suggest that the excitation light can be effectively guided along the glass capillary with a small amount of leakage through the scattering at the solutionair interface. Fluorescence emission of the analyte propagates in the radial direction of the glass capillary which can be efficiently captured by a smartphone camera through a miniaturized objective lens. Fluorescence intensity and spectra were characterized using Rhodamine 6G (R6G) with various concentrations. The emission was collected via a microscope with 5X magnification and a smartphone camera. Both experimental and simulation results suggest that the excitation rays are efficiently coupled into the glass micropipette tube for fluorescence excitation. The fluorescence emissions from the analyte will either pass along the glass tube or propagate in the radial direction collected by the detector. A limited amount of excitation leakage scattered from the liquid-air interface showed a minimal effect on fluorescence detection. We demonstrated the platform that combines the optofluidic micropipette and smartphone camera to detect steroid hormone.

Protein phosphorylation is one of the most prevalent signal transduction mechanisms that occurs within cells. This biochemical reaction follows an enzymatic reaction mechanism where the enzyme or kinase facilitates the transfer of the phosphate group from adenosine triphosphate (ATP) to the substrate protein. By monitoring this reaction in real-time, outside of the cell, the knowledge gained can be applied towards intracellular research in the future. Our goal is to combine microfluidic reactor technology with confocal Raman spectroscopy to investigate biochemical reactions such as protein phosphorylation in order to profile the reaction along the reactor path. By developing an approach that can monitor structural and conformational changes of proteins during biochemical reactions we can provide insight towards signal transduction mechanisms. Our reactor design is based off fluid dynamic principles and continuous reactor design equations. The change in concentration of a reagent during a reaction can be determined by a change in the intensity of its spectral response. The individual reagents for this particular protein phosphorylation reaction include protein kinase A, casein, ATP, a pseudosubstrate, as well as the three phosphorylatable amino acids: L-serine, L-threonine and L-tyrosine. Raman spectroscopy of varying concentrations of each individual reagent will quantify a change in concentration during the reaction. Concentration calibration curves were acquired on solutions inside the microreactor. Lower limit concentration detectability of the Raman instrument was also determined. Full Raman characterization of solid individual reagents was employed as a baseline for comparison of concentration measurements to monitor changes in reagents.

This report contains theoretical algorithm for the differential representation of a phase-inhomogeneous biological object as a set of consecutively located optically anisotropic layers; theoretical algorithms for the decomposition of the Mueller-matrix of the diffuse biological layer in the basis of differential matrices of the 1st and 2nd orders; analytical relations for determining the magnitude of the set of elements of differential matrices of the 1st and 2nd orders;information and characteristics of optical schemes of experimental devices.

In this paper are presented next research materials: • structural-logical scheme for diagnosing the limitation of death (LD) by the methods of polarizing microscopic tomography of the polycrystalline structure of vitreous preparations; • the temporal dynamics of necrotic changes in the coordinate distributions of the magnitude of the linear birefringence (LB) of the crystalline fraction of VB layers of the deceased; • the magnitudes and ranges of the temporal variation of the statistical moments of the 1st to the 4th orders characterizing the distributions of the LB value of the crystal fraction of the VB layers of the deceased; • efficiency and accuracy of LD determination by the method of polarization microscopic tomography LB polycrystalline component of the VB layers of the deceased; • the effectiveness of the use of wavelet analysis of the coordinate distributions of the LB value of a polycrystalline fraction of VB layers of the deceased in certain LD.

We investigated the effectiveness of the penetration of CNDs of various sizes into the articular cartilage of various degrees of degeneration affected by osteoarthritis. We performed quantitative evaluations by the intensity of the fluorescent image of the degenerated area of the articular cartilage in vitro. Using colorimetric MTT assay, we found that our CNDs did not have cytotoxic effects on the cellular level in vitro, and this allowed us to emphasize the prospects for using these nanoparticles as dyes for a considerable amount of observation time.