This PDF file contains the front matter associated with SPIE Proceedings Volume 10352 including the Title Page, Copyright information, Table of Contents, and Conference Committee listing.

Plasmonics is expected to make a tremendous impact in the field of life sciences, with applications in bioimaging, biosensing, targeted delivery and externally-triggered locoregional therapy. Plasmonic biosensors are considered to be highly promising for the development of simple, portable, sensitive, on-chip biodiagnostics for resource-limited settings such as at-home care, rural clinics, developing countries with low and moderate incomes and battle-field. While there has been a tremendous progress in the rational design of nanotransducers with high sensitivity and the development of hand-held read-out devices, the translation of these biosensors to resource-limited settings is hindered by the poor thermal, chemical, and environmental stability of the biorecogntion elements. “Cold-chain”, which is employed in the affluent parts of the world for reagent transport, storage, and handling, is expensive (capital cost of freezers, recurring cost of liquid nitrogen), environmentally unfriendly, and simply not feasible in resource-limited settings where electricity and refrigeration are not reliable or even available. Degradation of the sensitive reagents and biodiagnostic chips outside the cold-chain, compromises analytical validity, preventing accurate and timely diagnosis. We will present a novel class of plasmonic biosensors that rely artificial antibodies or peptide recognition elements with excellent thermal and chemical stability. In addition, we have recently introduced silk and metal-organic frameworks as protective coatings to stabilize natural antibodies bound to nanotransducers against thermal denaturation and loss of biorecognition. This multi-pronged approach overcomes the poor stability of existing plasmonic biosensors and takes them closer to real-world applications in resource-limited settings.

We demonstrate the advantage of using machine learning for surface enhanced Raman scattering (SERS) spectral analysis for quantitative detection of pyocyanin in Luria-Bertani media. Planar Au nanoparticle clusters were selfassembled on PS-b-PMMA diblock copolymer template using EDC crosslinking chemistry and electrohydrodynamic flow to fabricate SERS substrates. Resulting substrates produce uniform SERS response over large area with signal relative standard deviation of 10.8 % over 50 μm × 50 μm region. Taking advantage of the uniformity, 400 SERS spectra were collected at each pyocyanin concentration as training dataset. Tracking the intensity of pyocyanin 1350 cm-1 vibrational band shows linear regime beginning at 10 ppb. PLS analysis was also performed on the same training dataset. Without being explicitly “told” which spectrum to look for, PLS analysis recognizes the SERS spectrum of pyocyanin as its first loading vector even in the presence of other molecules in LB media. PLS regression enables quantitative detection at 1 ppb, 1 order of magnitude earlier than univariate regression. We hope this work will fuel a push toward wider adoption of more sophisticated machine learning algorithms for quantitative analysis of SERS spectra.

In recent years, the PROBE Lab at the University of Illinois at Urbana-Champaign has made significant developments in plasmonic nanoantenna technology by more closely exploring the rich parameter space associated with these structures including geometry and material composition, as well as the optical excitation conditions. Indeed, plasmonic nanoantennas are attractive for a variety of potential applications in nanotechnology, biology, and photonics due to their ability to tightly confine and strongly enhance optical fields. This talk will discuss our work with arrays of Au bowtie nanoantennas (BNAs) with an emphasis on how their field enhancement properties could be harnessed for particle manipulation and sensing. We also present our work with pillar-supported BNAs (p-BNAs) and discuss their potential for sensing applications, particularly when adapted for response in the near-IR. The talk will conclude with a brief discussion of some of the future work pursued by the PROBE lab, including adapting BNAs for lab-on-a-chip applications.

Phoropters are the most common instrument used to detect refractive errors. During a refractive exam, lenses are flipped in front of the patient who looks at the eye chart and tries to read the symbols. The procedure is fully dependent on the cooperation of the patient to read the eye chart, provides only a subjective measurement of visual acuity, and can at best provide a rough estimate of the patient’s vision. Phoropters are difficult to use for mass screenings requiring a skilled examiner, and it is hard to screen young children and the elderly etc. We have developed a simplified, lightweight automatic phoropter that can measure the optical error of the eye objectively without requiring the patient’s input. The automatic holographic adaptive phoropter is based on a Shack-Hartmann wave front sensor and three computercontrolled fluidic lenses. The fluidic lens system is designed to be able to provide power and astigmatic corrections over a large range of corrections without the need for verbal feedback from the patient in less than 20 seconds.

Ophthalmic surgery involves manipulation of delicate, layered tissue structures on milli- to micrometer scales. Traditional surgical microscopes provide an inherently two-dimensional view of the surgical field with limited depth perception which precludes accurate depth-resolved visualization of these tissue layers, and limits the development of novel surgical techniques. We demonstrate multimodal swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography (SS-SESLO-OCT) to address current limitations of image-guided ophthalmic microsurgery. SS-SESLO-OCT provides inherently co-registered en face and cross-sectional field-of-views (FOVs) at a line rate of 400 kHz and >2 GPix/s throughput. We show in vivo imaging of the anterior segment and retinal fundus of a healthy volunteer, and preliminary results of multi-volumetric mosaicking for ultrawide-field retinal imaging with 90° FOV. Additionally, a scan-head was rapid-prototyped with a modular architecture which enabled integration of SS-SESLO-OCT with traditional surgical microscope and slit-lamp imaging optics. Ex vivo surgical maneuvers were simulated in cadaveric porcine eyes. The system throughput enabled volumetric acquisition at 10 volumes-per-second (vps) and allowed visualization of surgical dynamics in corneal sweeps, compressions, and dissections, and retinal sweeps, compressions, and elevations. SESLO en face images enabled simple real-time co-registration with the surgical microscope FOV, and OCT cross-sections provided depth-resolved visualization of instrument-tissue interactions. Finally, we demonstrate novel augmented-reality integration with the surgical view using segmentation overlays to aid surgical guidance. SS-SESLO-OCT may benefit clinical diagnostics by enabling aiming, registration, and mosaicking; and intraoperative imaging by allowing for real-time surgical feedback, instrument tracking, and overlays of computationally extracted biomarkers of disease.

Sustained delivery of growth factors, proteins, drugs and other biologically active molecules is necessary for tissue engineering applications. Electrospun fibers are attractive tissue engineering scaffolds as they partially mimic the topography of the extracellular matrix (ECM). However, they do not provide continuous nourishment to the tissue. In search of a biomimetic scaffold for salivary gland tissue regeneration, we previously developed a blend nanofiber scaffold composed of the protein elastin and the synthetic polymer polylactic-co-glycolic acid (PLGA). The nanofiber scaffold promoted in vivo-like salivary epithelial cell tissue organization and apicobasal polarization. However, in order to enhance the salivary cell proliferation and biomimetic character of the scaffold, sustained growth factor delivery is needed. The composite nanofiber scaffold was optimized to act as a growth factor delivery system using epidermal growth factor (EGF) as a model protein. The nanofiber/EGF hybrid nanofibers were synthesized by double emulsion electrospinning where EGF is emulsified within a water/oil/water (w/o/w) double emulsion system. Successful incorporation of EGF was confirmed using Raman spectroscopy. EGF release profile was characterized using enzyme-linked immunosorbent assay (ELIZA) of the EGF content. Double emulsion electrospinning resulted in slower release of EGF. We demonstrated the potential of the proposed double emulsion electrospun nanofiber scaffold for the delivery of growth factors and/or drugs for tissue engineering and pharmaceutical applications.

Quantitative proteomics, as a developing method for study of proteins and identification of diseases, reveals more comprehensive and accurate information of an organism than traditional genomics. A variety of platforms, such as mass spectrometry, optical sensors, electrochemical sensors, magnetic sensors, etc., have been developed for detecting proteins quantitatively. The sandwich immunoassay is widely used as a labeled detection method due to its high specificity and flexibility allowing multiple different types of labels. While optical sensors use enzyme and fluorophore labels to detect proteins with high sensitivity, they often suffer from high background signal and challenges in miniaturization. Magnetic biosensors, including nuclear magnetic resonance sensors, oscillator-based sensors, Hall-effect sensors, and magnetoresistive sensors, use the specific binding events between magnetic nanoparticles (MNPs) and target proteins to measure the analyte concentration. Compared with other biosensing techniques, magnetic sensors take advantage of the intrinsic lack of magnetic signatures in biological samples to achieve high sensitivity and high specificity, and are compatible with semiconductor-based fabrication process to have low-cost and small-size for point-of-care (POC) applications. Although still in the development stage, magnetic biosensing is a promising technique for in-home testing and portable disease monitoring.

We present a new method for circulating tumor cell capture based on micro-array isolation from droplets. Called droplet biopsy, our technique uses a 76-element array of carbon nanotube devices functionalized with anti-EpCAM and antiHer2 antibodies for immunocapture of spiked breast cancer cells in the blood. This droplet biopsy chip can enable capture of CTCs based on both positive and negative selection strategy. Negative selection is achieved through depletion of contaminating leukocytes through the differential settling of blood into layers. We report 55%-100% cancer cell capture yield in this first droplet biopsy chip study. The droplet biopsy is an enabling idea where one can capture CTCs based on multiple biomarkers in a single blood sample.

As we aim to improve our understanding of the brain, it is critical that researchers have simultaneous multi-area, large-scale access to the brain. Information processing in the brain occurs through close and distant coupling of functional sub-domains, as opposed to within isolated single neurons. However, commercially available neural interfaces capable of sensing electrophysiology of single neurons, currently allow access to only a small, mm3 volume of cortical cells, are not scalable to recording from orders of magnitude more neurons, and leverage bulky, skull mounted hardware and cabling sensitive to relative movements of the skull and brain. In this work, we propose a system capable of recording from many individual distributed neural interrogator nodes, untethered from any external electronics. Using an array of epidural inductive coils to wirelessly power the implanted electronics, the system is intended to be agnostic to the surgical placement of any individual node. Here, we demonstrate the ability to transmit nearly 15mW of power with greater than 50% power transfer efficiency, benchtop testing of individual subcircuit system components showing successful digitization of neural signals, and wireless transmission currently supporting a data rate of 3.84Mbps. We leverage a software defined radio based RF receiver to demodulate the data which can be stored in memory for later retrieval. Finally, we introduce a packaging technology capable of isolating active electronics from the surrounding tissue while providing capability for electrical feed-through assemblies for external neural interfacing. We expect, based on the presented preliminary findings, that the system can be integrated into a platform technology for the study of the intricate interactions between cortical domains.

Optogenetic manipulation is widely used to selectively excite and silence neurons in laboratory experiments. Recent efforts to miniaturize the components of optogenetic systems have enabled experiments on freely moving animals, but further miniaturization is required for freely flying insects. In particular, miniaturization of high channel-count optical waveguides are needed for high-resolution interfaces. Thin flexible waveguide arrays are needed to bend light around tight turns to access small anatomical targets. We present the design of lightweight miniaturized optogentic hardware and supporting electronics for the untethered steering of dragonfly flight. The system is designed to enable autonomous flight and includes processing, guidance sensors, solar power, and light stimulators. The system will weigh less than 200mg and be worn by the dragonfly as a backpack. The flexible implant has been designed to provide stimuli around nerves through micron scale apertures of adjacent neural tissue without the use of heavy hardware. We address the challenges of lightweight optogenetics and the development of high contrast polymer waveguides for this purpose.

Despite recent advances in microfabrication and nanofabrication, integrating multiple modes of communication with the brain into a single biocompatible neural probe remains a challenge. These multifunctional neural probes may further our understanding of normal and disrupted functions of neural circuits manifested in neurological conditions, such as Parkinson’s disease. Here, we present a novel family of probes fabricated using a thermal drawing process. In this process, a macroscopic template (preform) containing the desired features is drawn by applying heat and tension into a fiber that conserves the original geometry of the preform but at a much smaller scale. Being composed of soft materials, such as polymers, conductive composites, and low melting temperature metals, fiber based neural probes minimize the damage to the surrounding tissue when implanted. Furthermore, fiber drawing enables straightforward integration features allowing for simultaneous electrical, optical and chemical interrogation of the brain. We demonstrate the utility of these probes for one-step optogenetics, in which a viral vector carrying opsin genes is injected through the same device then used to optically stimulate neurons and record their response as electrical activity. With these probes, we also show, for the first time, recordings of electrical activity in the spinal cord of freely moving mice.

Monitoring membrane potential in neurons requires sensors with minimal invasiveness, high spatial and temporal (sub-ms) resolution, and large sensitivity for enabling detection of sub-threshold activities. While organic dyes and fluorescent proteins have been developed to possess voltage-sensing properties, photobleaching, cytotoxicity, low sensitivity, and low spatial resolution have obstructed further studies. Semiconductor nanoparticles (NPs), as prospective voltage sensors, have shown excellent sensitivity based on Quantum confined Stark effect (QCSE) at room temperature and at single particle level. Both theory and experiment have shown their voltage sensitivity can be increased significantly via material, bandgap, and structural engineering. Based on theoretical calculations, we synthesized one of the optimal candidates for voltage sensors: 12 nm type-II ZnSe/CdS nanorods (NRs), with an asymmetrically located seed. The voltage sensitivity and spectral shift were characterized in vitro using spectrally-resolved microscopy using electrodes grown by thin film deposition, which “sandwich” the NRs. We characterized multiple batches of such NRs and iteratively modified the synthesis to achieve higher voltage sensitivity (ΔF/F> 10%), larger spectral shift (>5 nm), better homogeneity, and better colloidal stability. Using a high throughput screening method, we were able to compare the voltage sensitivity of our NRs with commercial spherical quantum dots (QDs) with single particle statistics. Our method of high throughput screening with spectrally-resolved microscope also provides a versatile tool for studying single particles spectroscopy under field modulation.

This paper presents our efforts in the development of a small wireless, flexible bandage sized near-infrared spectroscopy (NIRS) system for sleep analysis. The current size of the system is 2.8 cm × 1.7 cm × 0.6 cm. It is capable of performing NIRS with 660nm, 940nm and 850nm wavelengths for up to 11 hours continuously. The device is placed on the forehead to measure from the prefrontal cortex and the raw data is continuously streamed over Bluetooth to a nearby data aggregator such as a smartphone for post processing and cloud connection. In this study, we performed traditional polysomnography simultaneously with NIRS to evaluate agreement with traditional measures of sleep and to provide labelled data for future work involving learning algorithms. Ultimately, we expect a machine learning algorithm to be able to generate characterization of sleep states comparable to traditional methods based on this biophotonics data. The system also includes an inertial measurement unit and the features that can be extracted from the presented system include sleep posture, heart rate, respiratory rate, relative change in oxy and deoxy hemoglobin concentrations and tissue oxygenation and cerebral arterial oxygen extracted from these. Preliminary proof of concept results are promising and demonstrate the capability to measure heart rate, respiratory rate and slow-wave-sleep stages. This system serves as a prototype to evaluate the potential of a small bandage-size continuous-wave NIRS device to be a useful means of studying sleep.

High aspect-ratio elastomeric micropillars are widely used in a plethora of applications, such as functional surfaces, actuators, and sensors. Their fabrication at arbitrary positions on non-planar substrates, however, has rarely been reported. Here we demonstrate a new technique for facile fabrication of high aspect-ratio, microsphere-tipped elastomeric micropillars on structures with uncommon geometries. As a proof-of-concept exemplary application, a fiber optic contact sensor is realized by integrating a micropillar onto the end facet of an optical fiber. Overall, both the fabrication technique and the resulting outcomes of this work will add new tools to the toolbox of soft-MEMS and softrobotics.

In the approximation of weak phase fluctuations, a polarization-correlation method for diagnosing the optical anisotropy of small-scale optically anisotropic fibrillar structures of myocardial tissues is proposed.The algorithms of analytical description and experimental determination of the coordinate distributions of the value of the modulus and phase of "two-point" Stokes vector parameters are defined. Within the statistic, correlation and fractal analysis the possibility of differential diagnostics of slight changes in optical anisotropy of myocardial tissues of different pathological states. The comparative analysis of objective statistical, correlation and fractal analysis of distributions of "single-point" polarization azimuth and ellipticity and "two-point" Stokes vector parameters of polarization-inhomogeneous images of the studied histological sections demonstrated excellent accuracy ( Ac >90% ) of differential diagnostics of changes in the optical anisotropy myocardium tissues.

The paper presents the results of polarization manifestations of small - and Large-scale phase anisotropy of dead in consequence of ischemic heart disease (IHD) and acute coronary insufficiency (ACI) people myocardial tissue structures to differentiate information, the wavelet analysis method is used. The resulting maps of the of the polarizationcorrelation parameters distributions (the phase of the two-point first and second parameters of the Stokes vector) are analyzed in the framework of statistical approach. On this basis, the criteria for differential diagnosis of IHD and ACI cases have been determined.

First pristine graphene was successfully produced by mechanical exfoliation and electrically characterized in 2004 by Andre Geim and Konstantin Novoselov at University of Manchester. Since its discovery in 2004, graphene also known as ‘super’ material that has enticed many researchers and engineers to explore its potential in ultrasensitive detection of analytes in biosensing applications. Among myriad reported sensors, biosensors based on field effect transistors (FETs) have attracted much attention. Thus, implementing graphene as conducting channel material hastens the opportunities for production of ultrasensitive biosensors for future device applications. Herein, we have reported electrical characteristics of graphene based field effect transistor (GFET) for ADH detection. GFET was modelled and simulated using Lumerical DEVICE charge transport solver (DEVICE CT). Electrical characteristics comprising of transfer and output characteristics curves are reported in this study. The device shows ambipolar curve and achieved a minimum conductivity of 0.23912 e⁵A at Dirac point. However, the curve shifts to the left and introduces significant changes in the minimum conductivity as drain voltage is increased. Output characteristics of GFET exhibits linear I_d - V_d dependence characteristics for gate voltage ranging from 0 to 1.5 V. In addition, behavior of electrical transport through GFET was analyzed for various simulation temperatures. It clearly proves that the electrical transport in GFET is dependent on the simulation temperature as it may vary the maximum resistance in channel of the device. Therefore, this unique electrical characteristics of GFET makes it as a promising candidate for ultrasensitive detection of small biomolecules such as ADH in biosensing applications.

The model of the azimuthally invariant Mueller-matrix description of polarization-correlation mechanisms of optical anisotropy that typical for polycrystalline layers of the histological sections of biological tissues is suggested. Within the statistical analysis of the ranges of linear and circular birefringence, dichroism, the objective criteria for the differentiation of myocardium histological sections were determined. From the point of view of probative medicine the ranges of variation of the statistical parameters that characterize the Mueller-matrix invariants of optical anisotropy parameters were found.

A new method of Stokes correlometry of polarization-inhomogeneous images of biological layers is presented. Analytic relations are determined for the modulus of complex parameters of the Stokes vector. A technique for measuring the coordinate distributions of the magnitude of the two-point modulus of the Stokes vector is proposed. Objective criteria for differentiating the optical anisotropy of polycrystalline urine films of healthy donors and patients with albuminuria have been found. An excellent level of balanced accuracy of differential diagnostics has been achieved.

The antimicrobial activity of silver nanoparticles has been extensively studied in the last years. Such nanoparticles constitute a potential and promising approach for the development of new antimicrobial systems especially due to the fact that several microorganisms are developing resistance to some already existing antimicrobial agents, therefore making antibacterial and antimicrobial studies on alternative materials necessary to overcome this issue. Silver nanoparticle concentration and size are determining factors on the antimicrobial activity of these nano systems. Heparin is a polysaccharide that belongs to the glycosaminoglycans (GAGs) family, molecules formed by a base disaccharide whose components are joined by a glycosidic linkage that is a repeating unit along their structure. It is highly sulfated making it a negatively charged material that is also widely used as an anticoagulant in Medicine because its biocompatibility besides it is also produced within the human body, specifically in the mast cells. Heparin alone possesses antimicrobial activity although it has not been studied very much in detail, it only has been demonstrated that it inhibits E. coli, P. aeruginosa, S. aureus and S. epidermidis, so taking this into account, this study is dedicated to assess UV photochemically-synthesized (λ=254 nm) heparin-based silver nanoparticles antimicrobial activity using the agar disk diffusion method complemented by the broth microdilution method to estimate de minimum inhibitory concentration (MIC), that is the lowest concentration at which an antimicrobial will inhibit visible growth of a microorganism. The strains used were the ones aforementioned to assess the antimicrobial activity degree these heparinbased nanoparticles exhibit.

It has been proposed the optical model of Jones-matrix description of mechanisms of optical anisotropy of polycrystalline films of human bile, namely optical activity and birefringence. The algorithm of reconstruction of distributions of parameters - optical rotation angles and phase shifts of the indicated anisotropy types has been elaborated. The objective criteria of differentiation of bile films taken from healthy donors and patients with cholelithiasis by means of statistic analysis of such distributions have been determined. The operational characteristics (sensitivity, specificity and accuracy) of Jones-matrix reconstruction method of optical anisotropy parameters were defined.

Hydroquinone is an aromatic organic molecule found in skin lightening creams for dermatological melasma treatment. The absorbance of this substance at high concentrations can be the cause of skin diseases. Nowadays most of the methods used for medical diagnosis for dermatological diseases consist on invasive methods such as biopsies. In recent years non-invasive techniques based on the properties of light and the interaction with biological samples have come to a new way for medical diagnosis. By means of Raman spectroscopy is of great interest the detection of hydroquinone for future medical applications. Due to the low Raman signal that the biological samples present, it is necessary to make use of nanotechnology. Making biosensors (SERS substrates) that allow us to amplify the electromagnetic field for the biological Raman signals.