Proceedings Volume 9699

Optics and Biophotonics in Low-Resource Settings II

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Proceedings Volume 9699

Optics and Biophotonics in Low-Resource Settings II

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Volume Details

Date Published: 23 May 2016
Contents: 8 Sessions, 21 Papers, 19 Presentations
Conference: SPIE BiOS 2016
Volume Number: 9699

Table of Contents

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Table of Contents

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  • Front Matter: Volume 9699
  • Lab-On-a-Chip Methods
  • Fabrication and 3D Printing in Optical Systems
  • Fluorescence and Polarization Methods
  • Translational Research I: Microscopy Plus White Light Imaging
  • Blood Diagnostics
  • Translational Research II: New Technologies and Implementations
  • Poster Session
Front Matter: Volume 9699
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Front Matter: Volume 9699
This PDF file contains the front matter associated with SPIE Proceedings Volume 9699, including the Title Page, Copyright information, Table of Contents, Invited Panel Discussion, and Conference Committee listing.
Lab-On-a-Chip Methods
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Digital detection of biomarkers for high-sensitivity diagnostics at low-cost
M. Selim Ünlü, John Connor, Steve Scherr, et al.
We have demonstrated Interferometric Reflectance Imaging Sensor (IRIS) with the ability to detect single nanoscale particles. By extending single-particle IRIS to in-liquid dynamic imaging, we demonstrated real-time digital detection of individual viral pathogens as well as single molecules labeled with Au nanoparticles. With this technique we demonstrate real-time simultaneous detection of multiple targets in a single sample, as well as quantitative dynamic detection of individual biomolecular interactions for reaction kinetics measurements. This approach promises to simplify and reduce the cost of rapid diagnostics.
Single DNA imaging and length quantification through a mobile phone microscope
Qingshan Wei, Wei Luo, Samuel Chiang, et al.
The development of sensitive optical microscopy methods for the detection of single DNA molecules has become an active research area which cultivates various promising applications including point-of-care (POC) genetic testing and diagnostics. Direct visualization of individual DNA molecules usually relies on sophisticated optical microscopes that are mostly available in well-equipped laboratories. For POC DNA testing/detection, there is an increasing need for the development of new single DNA imaging and sensing methods that are field-portable, cost-effective, and accessible for diagnostic applications in resource-limited or field-settings. For this aim, we developed a mobile-phone integrated fluorescence microscopy platform that allows imaging and sizing of single DNA molecules that are stretched on a chip. This handheld device contains an opto-mechanical attachment integrated onto a smartphone camera module, which creates a high signal-to-noise ratio dark-field imaging condition by using an oblique illumination/excitation configuration. Using this device, we demonstrated imaging of individual linearly stretched λ DNA molecules (48 kilobase-pair, kbp) over 2 mm2 field-of-view. We further developed a robust computational algorithm and a smartphone app that allowed the users to quickly quantify the length of each DNA fragment imaged using this mobile interface. The cellphone based device was tested by five different DNA samples (5, 10, 20, 40, and 48 kbp), and a sizing accuracy of <1 kbp was demonstrated for DNA strands longer than 10 kbp. This mobile DNA imaging and sizing platform can be very useful for various diagnostic applications including the detection of disease-specific genes and quantification of copy-number-variations at POC settings.
NutriPhone: vitamin B12 testing on your smartphone (Conference Presentation)
Seoho Lee, Dakota O'Dell, Jessica Hohenstein, et al.
Vitamin B12 deficiency is the leading cause of cognitive decline in the elderly and is associated with increased risks of several acute and chronic conditions including anemia. The deficiency is prevalent among the world population, most of whom are unaware of their condition due to the lack of a simple diagnostics system. Recent advancements in the smartphone-enabled mobile health can help address this problem by making the deficiency tests more accessible. Previously, our group has demonstrated the NutriPhone, a smartphone platform for the accurate quantification of vitamin D levels. The NutriPhone technology comprises of a disposable test strip that performs a colorimetric reaction upon collecting a sample, a reusable accessory that interfaces with the smartphone camera, and a smartphone app that stores the algorithm for analyzing the test-strip reaction. In this work, we show that the NutriPhone can be expanded to measure vitamin B12 concentrations by developing a lateral flow assay for B12 that is compatible with our NutriPhone system. Our novel vitamin B12 assay incorporates blood sample processing and key reagent storage on-chip, which advances it into a sample-in-answer-out format that is suitable for point-of-care diagnostic applications. In order to enable the detection of pM levels of vitamin B12 levels, silver amplification of the initial signal is used within the total assay time of less than 15 minutes. We demonstrate the effectiveness of our NutriPhone system by deploying it in a resource-limited clinical setting in India where it is used to test tens of participants for vitamin B12 deficiency.
Cellphone-based hand-held microplate reader for point-of-care ELISA testing (Conference Presentation)
Brandon Berg, Bingen Cortazar, Derek Tseng, et al.
Enzyme-linked immunosorbent assay (ELISA) in a microplate format has been a gold standard first-line clinical test for diagnosis of various diseases including infectious diseases. However, this technology requires a relatively large and expensive multi-well scanning spectrophotometer to read and quantify the signal from each well, hindering its implementation in resource-limited-settings. Here, we demonstrate a cost-effective and handheld smartphone-based colorimetric microplate reader for rapid digitization and quantification of immunoserology-related ELISA tests in a conventional 96-well plate format at the point of care (POC). This device consists of a bundle of 96 optical fibers to collect the transmitted light from each well of the microplate and direct all the transmission signals from the wells onto the camera of the mobile-phone. Captured images are then transmitted to a remote server through a custom-designed app, and both quantitative and qualitative diagnostic results are returned back to the user within ~1 minute per 96-well plate by using a machine learning algorithm. We tested this mobile-phone based micro-plate reader in a clinical microbiology lab using FDA-approved mumps IgG, measles IgG, and herpes simplex virus IgG (HSV-1 and HSV-2) ELISA tests on 1138 remnant patient samples (roughly 50% training and 50% testing), and achieved an overall accuracy of ~99% or higher for each ELISA test. This handheld and cost-effective platform could be immediately useful for large-scale vaccination monitoring in low-infrastructure settings, and also for other high-throughput disease screening applications at POC.
Fabrication and 3D Printing in Optical Systems
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Low cost flatbed scanner label-free biosensor
Ugur Aygun, Oguzhan Avci, Elif Seymour, et al.
In this paper, we demonstrate utilization of a commercial flatbed document scanner as a label-free biosensor for highthroughput imaging of DNA and protein microarrays. We implemented an interferometric sensing technique through use of a silicon/oxide layered substrate, and easy to implement hardware modifications such as re-aligning moving parts and inserting a custom made sample plate. With a cost as low as 100USD, powered by a USB cable, and scan speed of 30 seconds for a 4mm x 4 mm area with ~10μm lateral resolution, the presented system offers a super low cost, easy to use alternative to commercially available label-free systems.
Development and bench testing of a multi-spectral imaging technology built on a smartphone platform
Frank J. Bolton, Reuven Weiser, Alex J. Kass, et al.
Cervical cancer screening presents a great challenge for clinicians across the developing world. In many countries, cervical cancer screening is done by visualization with the naked eye. Simple brightfield white light imaging with photo documentation has been shown to make a significant impact on cervical cancer care. Adoption of smartphone based cervical imaging devices is increasing across Africa. However, advanced imaging technologies such as multispectral imaging systems, are seldom deployed in low resource settings, where they are needed most. To address this challenge, the optical system of a smartphone-based mobile colposcopy imaging system was refined, integrating components required for low cost, portable multi-spectral imaging of the cervix. This paper describes the refinement of the mobile colposcope to enable it to acquire images of the cervix at multiple illumination wavelengths, including modeling and laboratory testing. Wavelengths were selected to enable quantifying the main absorbers in tissue (oxyand deoxy-hemoglobin, and water), as well as scattering parameters that describe the size distribution of scatterers. The necessary hardware and software modifications are reviewed. Initial testing suggests the multi-spectral mobile device holds promise for use in low-resource settings.
Mechanical and optical behavior of a tunable liquid lens using a variable cross section membrane: modeling results
A lens containing a liquid medium and having at least one elastic membrane as one of its components is known as an elastic membrane lens (EML). The elastic membrane may have a constant or variable thickness. The optical properties of the EML change by modifying the profile of its elastic membrane(s). The EML formed of elastic constant thickness membrane(s) have been studied extensively. However, EML information using elastic membrane of variable thickness is limited. In this work, we present simulation results of the mechanical and optical behavior of two EML with variable thickness membranes (convex-plane membranes). The profile of its surfaces were modified by liquid medium volume increases. The model of the convex-plane membranes, as well as the simulation of its mechanical behavior, were performed using Solidworks® software; and surface’s points of the deformed elastic lens were obtained. Experimental stress-strain data, obtained from a silicone rubber simple tensile test, according to ASTM D638 norm, were used in the simulation. Algebraic expressions, (Schwarzschild formula, up to four deformation coefficients, in a cylindrical coordinate system (r, z)), of the meridional profiles of the first and second surfaces of the deformed convex-plane membranes, were obtained using the results from Solidworks® and a program in the software Mathematica®. The optical performance of the EML was obtained by simulation using the software OSLO® and the algebraic expressions obtained in Mathematica®.
Development of a miniature multiple reference optical coherence tomography imaging device
Paul M. McNamara, Colm O'Riordan, Seán Collins, et al.
Multiple reference optical coherence tomography (MR-OCT) is a new technology ideally suited to low-cost, compact OCT imaging. This modality is an extension of time-domain OCT with the addition of a partial mirror in front of the reference mirror. This enables extended, simultaneous depth scanning with the relatively short sweep of a miniature voice coil motor on which the scanning mirror is mounted. Applications of this technology include biometric security, ophthalmology, personal health monitoring and non-destructive testing. This work details early-stage development of the first iteration of a miniature MR-OCT device. This device utilizes a fiber-coupled input from an off-board superluminescent diode (SLD). Typical dimensions of the module are 40 × 57 mm, but future designs are expected to be more compact. Off-the-shelf miniature optical components, voice coil motors and photodetectors are used, with the complexity of design depending on specific applications. The photonic module can be configured as either polarized or non-polarized and can include balanced detection. The photodetectors are directly connected to a printed circuit board under the module containing a transimpedance amplifier with complimentary outputs. The results shown in this work are from the non-polarized device. Assembly of the photonic modules requires extensive planning. In choosing the optical components, Zemax simulations are performed to model the beam characteristics. The physical layout is modeled using Solidworks and each component is placed and aligned via a well-designed alignment procedure involving an active-alignment pick-and-place assembly system.
Wavelength scanning achieves pixel super-resolution in holographic on-chip microscopy
Wei Luo, Zoltan Göröcs, Yibo Zhang, et al.
Lensfree holographic on-chip imaging is a potent solution for high-resolution and field-portable bright-field imaging over a wide field-of-view. Previous lensfree imaging approaches utilize a pixel super-resolution technique, which relies on sub-pixel lateral displacements between the lensfree diffraction patterns and the image sensor’s pixel-array, to achieve sub-micron resolution under unit magnification using state-of-the-art CMOS imager chips, commonly used in e.g., mobile-phones. Here we report, for the first time, a wavelength scanning based pixel super-resolution technique in lensfree holographic imaging. We developed an iterative super-resolution algorithm, which generates high-resolution reconstructions of the specimen from low-resolution (i.e., under-sampled) diffraction patterns recorded at multiple wavelengths within a narrow spectral range (e.g., 10-30 nm). Compared with lateral shift-based pixel super-resolution, this wavelength scanning approach does not require any physical shifts in the imaging setup, and the resolution improvement is uniform in all directions across the sensor-array. Our wavelength scanning super-resolution approach can also be integrated with multi-height and/or multi-angle on-chip imaging techniques to obtain even higher resolution reconstructions. For example, using wavelength scanning together with multi-angle illumination, we achieved a halfpitch resolution of 250 nm, corresponding to a numerical aperture of 1. In addition to pixel super-resolution, the small scanning steps in wavelength also enable us to robustly unwrap phase, revealing the specimen’s optical path length in our reconstructed images. We believe that this new wavelength scanning based pixel super-resolution approach can provide competitive microscopy solutions for high-resolution and field-portable imaging needs, potentially impacting tele-pathology applications in resource-limited-settings.
Fluorescence and Polarization Methods
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Evaluation of a polarization sensitive multiple reference optical coherence tomography system
Sean O'Gorman, Paul M. McNamara, Roshan Dsouza, et al.
Multiple reference optical coherence tomography (MR-OCT) is a new compact optical sensor platform based on a small form factor recirculating reference arm scanning optical delay, which promises a robust, cost-effective semisolid state design for integration with next generation mobile devices. The miniature re-circulating optical delay is based on a voice coil motor (VCM) actuator and a partial mirror. Imaging capability of MR-OCT has been recently demonstrated using a non-polarizing bulk optics design and an unbalanced detection system with a sensitivity of up to 98 dB at an axial rate of 1200 A-scans per second. In this study, we implemented a polarization based MR-OCT with balanced detection system and have gathered preliminary results in comparison with a non-polarizing MROCT with balanced detection. The polarization sensitive (PS)-MR-OCT, based on a balanced detection scheme can improve the sensitivity by reducing common-mode noise of the system.
Wide-field synovial fluid imaging using polarized lens-free on-chip microscopy for point-of-care diagnostics of gout (Conference Presentation)
Yibo Zhang, Seung Yoon Lee, Yun Zhang, et al.
Gout and pseudogout are forms of crystal arthropathy caused by monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPPD) crystals in the joint, respectively, that can result in painful joints. Detecting the unique-shaped, birefringent MSU/CPPD crystals in a synovial fluid sample using a compensated polarizing microscope has been the gold-standard for diagnosis since the 1960’s. However, this can be time-consuming and inaccurate, especially if there are only few crystals in the fluid. The high-cost and bulkiness of conventional microscopes can also be limiting for point-of-care diagnosis. Lens-free on-chip microscopy based on digital holography routinely achieves high-throughput and high-resolution imaging in a cost-effective and field-portable design. Here we demonstrate, for the first time, polarized lens-free on-chip imaging of MSU and CPPD crystals over a wide field-of-view (FOV ~ 20.5 mm2, i.e., <20-fold larger compared a typical 20X objective-lens FOV) for point-of-care diagnostics of gout and pseudogout. Circularly polarizer partially-coherent light is used to illuminate the synovial fluid sample on a glass slide, after which a quarter-wave-plate and an angle-mismatched linear polarizer are used to analyze the transmitted light. Two lens-free holograms of the MSU/CPPD sample are taken, with the sample rotated by 90, to rule out any non-birefringent objects within the specimen. A phase-recovery algorithm is also used to improve the reconstruction quality, and digital pseudo-coloring is utilized to match the color and contrast of the lens-free image to that of a gold-standard microscope image to ease the examination by a rheumatologist or a laboratory technician, and to facilitate computerized analysis.
Rapid and sensitive detection of waterborne pathogens using machine learning on a smartphone based fluorescence microscope (Conference Presentation)
Hatice Ceylan Koydemir, Zoltan Goracs, Derek Tseng, et al.
Abstract not available.
Translational Research I: Microscopy Plus White Light Imaging
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Mobile colposcopy in urban and underserved suburban areas in Baja California
Marta Madiedo, Sonia Contreras, Octavio Villalobos, et al.
Cervical cancer is the leading cause of cancer death for women in low resource settings, often affecting the most economically disenfranchised segment of the population. The key challenge with cervical cancer is the lack of an effective screening program for many of the at-risk, difficult-to-reach women. Outreach programs that utilize mobile clinics to increase access to screening and care in Baja California have been developed. However, many barriers such as quality assurance, efficient referral remained a challenge in this region. Visualization-based co-tests together with cytology (Pap smears) as a primary screen have been proposed. Here, the mobile colposcope of the enhanced visual assessment (EVA) is used to capture an image immediately following a Pap smear. EVA images were reviewed by expert colposcopists. Initial or preliminary data from pilot services showed that Pap false positives and Pap false negatives maybe reduced by expert review of EVA images. This suggests that reviewing of EVA images may be instrumental in catching inaccurate Pap results, thereby improving care. Thus, there is a need to further explore the benefits of using EVA as additional information when conducting Pap smear screenings.
Field-testing of a cost-effective mobile-phone based microscope for screening of Schistosoma haematobium infection (Conference Presentation)
Hatice Ceylan Koydemir, Isaac I. Bogoch, Derek Tseng, et al.
Schistosomiasis is a parasitic and neglected tropical disease, and affects <200-million people across the world, with school-aged children disproportionately affected. Here we present field-testing results of a handheld and cost effective smartphone-based microscope in rural Ghana, Africa, for point-of-care diagnosis of S. haematobium infection. In this mobile-phone microscope, a custom-designed 3D printed opto-mechanical attachment (~150g) is placed in contact with the smartphone camera-lens, creating an imaging-system with a half-pitch resolution of ~0.87µm. This unit includes an external lens (also taken from a mobile-phone camera), a sample tray, a z-stage to adjust the focus, two light-emitting-diodes (LEDs) and two diffusers for uniform illumination of the sample. In our field-testing, 60 urine samples, collected from children, were used, where the prevalence of the infection was 72.9%. After concentration of the sample with centrifugation, the sediment was placed on a glass-slide and S. haematobium eggs were first identified/quantified using conventional benchtop microscopy by an expert diagnostician, and then a second expert, blinded to these results, determined the presence/absence of eggs using our mobile-phone microscope. Compared to conventional microscopy, our mobile-phone microscope had a diagnostic sensitivity of 72.1%, specificity of 100%, positive-predictive-value of 100%, and a negative-predictive-value of 57.1%. Furthermore, our mobile-phone platform demonstrated a sensitivity of 65.7% and 100% for low-intensity infections (≤50 eggs/10 mL urine) and high-intensity infections (<50 eggs/10 mL urine), respectively. We believe that this cost-effective and field-portable mobile-phone microscope may play an important role in the diagnosis of schistosomiasis and various other global health challenges.
Custom field-of-view optofluidic imaging by synthetic digital holography
V. Bianco, M. Paturzo, V. Marchesano, et al.
A recently proposed imaging modality, named Space-Time Scanning Interferometry (STSI), exploits object scanning to synthesize interferograms mapped in a hybrid space-time domain. A single linear sensor array is sufficient to create such interferograms with unlimited Field of View (FoV) along the scanning direction. If properly selected, three detector lines allows to recovery the phase information by Phase Shifting (PS) interferometry algorithms. Here we show the application of the STSI method to microfluidic imaging of biological samples, where the required phase shift between interferograms is intrinsically offered due to the sample movement, i.e. scanning does not need to be provided. Besides, out-of-focus recordings are performed using a single line detector, in order to synthesize an unlimited FoV Space-Time Digital Hologram (STDH). As conventional DH, a STDH yields full-field, quantitative, flexible focusing imaging. In addition, in a STDH the FoV is customizable in one direction, so that the desired magnification of a large size sample can be set, still being able to image this entirely. Besides, STDH allows to capture data from a multitude of flowing samples and to process the corresponding information in a single operation, thus avoiding hologram stitching. Experiments have been carried out to demonstrate the capability of STDH provide very high-throughput imaging of objects flowing in a liquid volume using a linear sensor array easily embeddable onboard LoC platforms.
Blood Diagnostics
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Portable point-of-care blood analysis system for global health (Conference Presentation)
James J. Dou, James Stewart Aitchison, Lu Chen, et al.
In this paper we present a portable blood analysis system based on a disposable cartridge and hand-held reader. The platform can perform all the sample preparation, detection and waste collection required to complete a clinical test. In order to demonstrate the utility of this approach a CD4 T cell enumeration was carried out. A handheld, point-of-care CD4 T cell system was developed based on this system. In particular we will describe a pneumatic, active pumping method to control the on-chip fluidic actuation. Reagents for the CD4 T cell counting assay were dried on a reagent plug to eliminate the need for cold chain storage when used in the field. A micromixer based on the active fluidic actuation was designed to complete sample staining with fluorescent dyes that was dried on the reagent plugs. A novel image detection and analysis algorithm was developed to detect and track the flight of target particles and cells during each analysis. The handheld, point-of-care CD4 testing system was benchmarked against clinical cytometer. The experimental results demonstrated experimental results were closely matched with the flow cytometry. The same platform can be further expanded into a bead-array detection system where other types of biomolecules such as proteins can be detected using the same detection system.
Thumb-size ultrasonic-assisted spectroscopic imager for in-situ glucose monitoring as optional sensor of conventional dialyzers
Kosuke Nogo, Keita Mori, Wei Qi, et al.
We proposed the ultrasonic-assisted spectroscopic imaging for the realization of blood-glucose-level monitoring during dialytic therapy. Optical scattering and absorption caused by blood cells deteriorate the detection accuracy of glucose dissolved in plasma. Ultrasonic standing waves can agglomerate blood cells at nodes. In contrast, around anti-node regions, the amount of transmitted light increases because relatively clear plasma appears due to decline the number of blood cells. Proposed method can disperse the transmitted light of plasma without time-consuming pretreatment such as centrifugation. To realize the thumb-size glucose sensor which can be easily attached to dialysis tubes, an ultrasonic standing wave generator and a spectroscopic imager are required to be small. Ultrasonic oscillators are ∅30[mm]. A drive circuit of oscillators, which now size is 41×55×45[mm], is expected to become small. The trial apparatus of proposed one-shot Fourier spectroscopic imager, whose size is 30×30×48[mm], also can be little-finger size in principal. In the experiment, we separated the suspension mixed water and micro spheres (Θ10[mm) into particles and liquid regions with the ultrasonic standing wave (frequency: 2[MHz]). Furthermore, the spectrum of transmitted light through the suspension could be obtained in visible light regions with a white LED.
Phase-sensitive multiple reference optical coherence tomography (Conference Presentation)
Multiple reference OCT (MR-OCT) is a recently developed novel time-domain OCT platform based on a miniature reference arm optical delay, which utilizes a single miniature actuator and a partial mirror to generate recirculating optical delay for extended axial-scan range. MR-OCT technology promises to fit into a robust and cost-effective design, compatible with integration into consumer-level devices for addressing wide applications in mobile healthcare and biometry applications. Using conventional intensity based OCT processing techniques, the high-resolution structural imaging capability of MR-OCT has been recently demonstrated for various applications including in vivo human samples. In this study, we demonstrate the feasibility of implementing phase based processing with MR-OCT for various functional applications such as Doppler imaging and sensing of blood vessels, and for tissue vibrography applications. The MR-OCT system operates at 1310nm with a spatial resolution of ~26 µm and an axial scan rate of 600Hz. Initial studies show a displacement-sensitivity of ~20 nm to ~120 nm for the first 1 to 9 orders of reflections, respectively with a mirror as test-sample. The corresponding minimum resolvable velocity for these orders are ~2.3 µm/sec and ~15 µm/sec respectively. Data from a chick chorioallantoic membrane (CAM) model will be shown to demonstrate the feasibility of MR-OCT for imaging in-vivo blood flow.
The impact of relative intensity noise on the signal in multiple reference optical coherence tomography
Multiple reference optical coherence tomography (MR-OCT) applies a unique low-cost solution to enhance the scanning depth of standard time domain OCT by inserting an partial mirror into the reference arm of the interferometric system. This novel approach achieves multiple reflections for different layers and depths of an sample with minimal effort of engineering and provides an excellent platform for low-cost OCT systems based on well understood production methods for micro-mechanical systems such as CD/DVD pick-up systems. The direct integration of a superluminescent light-emitting diode (SLED) is a preferable solution to reduce the form- factor of an MR-OCT system. Such direct integration exposes the light source to environmental conditions that can increase fluctuations in heat dissipation and vibrations and affect the noise characteristics of the output spectrum. This work describes the impact of relative intensity noise (RIN) on the quality of the interference signal of MR-OCT related to a variety of environmental conditions, such as temperature.
Flat lensless phase imager
Manon Rostykus, Christophe Moser
Lensless imaging refers to an imaging technique which requires no imaging element between the light transmitted by the sample and the camera. This configuration enables designing compact devices. In the visible range, it is mainly investigated for microscopy, because of the high resolution (sub-micrometer) and large field of view (camera chip size) that it provides. Current implementations use illumination sources positioned above the sample several centimeters away making the lensless imager bulky in height. Here we demonstrate an implementation with the illumination sources side illuminating a Dove prism onto which analog holograms are laminated. Diffraction from the analog holograms provides the multiple angle illumination. This results in a flat phase lensless imager.
Translational Research II: New Technologies and Implementations
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Initial clinical testing of a multi-spectral imaging system built on a smartphone platform
Jonah W. Mink, Shraga Wexler, Frank J. Bolton, et al.
Multi-spectral imaging systems are often expensive and bulky. An innovative multi-spectral imaging system was fitted onto a mobile colposcope, an imaging system built around a smartphone in order to image the uterine cervix from outside the body. The multi-spectral mobile colposcope (MSMC) acquires images at different wavelengths. This paper presents the clinical testing of MSMC imaging (technical validation of the MSMC system is described elsewhere

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). Patients who were referred to colposcopy following abnormal screening test (Pap or HPV DNA test) according to the standard of care were enrolled. Multi-spectral image sets of the cervix were acquired, consisting of images from the various wavelengths. Image acquisition took 1-2 sec. Areas suspected for dysplasia under white light imaging were biopsied, according to the standard of care. Biopsied sites were recorded on a clockface map of the cervix. Following the procedure, MSMC data was processed from the sites of biopsied sites. To date, the initial histopathological results are still outstanding. Qualitatively, structures in the cervical images were sharper at lower wavelengths than higher wavelengths. Patients tolerated imaging well. The result suggests MSMC holds promise for cervical imaging.
Quantitative wound healing studies using a portable, low cost, handheld near-infrared optical scanner: preliminary sensitivity and specificity analysis
Jiali Lei, Suset Rodriguez, Maanasa Jayachandran, et al.
Lower extremity ulcers are devastating complications that are still un-recognized. To date, clinicians employ visual inspection of the wound site during its standard 4-week of healing process via monitoring of surface granulation. A novel ultra-portable near-infrared optical scanner (NIROS) has been developed at the Optical Imaging Laboratory that can perform non-contact 2D area imaging of the wound site. From preliminary studies it was observed that the nonhealing wounds had a greater absorption contrast with respect to the normal site, unlike in the healing wounds. Currently, non-contact near-infrared (NIR) imaging studies were carried out on 22 lower extremity wounds at two podiatric clinics, and the sensitivity and specificity of the scanner evaluated. A quantitative optical biometric was developed that differentiates healing from non-healing wounds, based on the threshold values obtained during ROC analysis. In addition, optical images of the wound obtained from weekly imaging studies are also assessed to determine the ability of the device to predict wound healing consistently on a periodic basis. This can potentially impact early intervention in the treatment of lower extremity ulcers when an objective and quantitative wound healing approach is developed. Lastly, the incorporation of MATLAB graphical user interface (GUI) to automate the process of image acquisition, image processing and image analysis realizes the potential of NIROS to perform non-contact and real-time imaging on lower extremity wounds.
A game-based crowdsourcing platform for rapidly training middle and high school students to perform biomedical image analysis
Steve Feng, Min-jae Woo, Hannah Kim, et al.
We developed an easy-to-use and widely accessible crowd-sourcing tool for rapidly training humans to perform biomedical image diagnostic tasks and demonstrated this platform’s ability on middle and high school students in South Korea to diagnose malaria infected red-blood-cells (RBCs) using Giemsa-stained thin blood smears imaged under light microscopes. We previously used the same platform (i.e., BioGames) to crowd-source diagnostics of individual RBC images, marking them as malaria positive (infected), negative (uninfected), or questionable (insufficient information for a reliable diagnosis). Using a custom-developed statistical framework, we combined the diagnoses from both expert diagnosticians and the minimally trained human crowd to generate a gold standard library of malaria-infection labels for RBCs. Using this library of labels, we developed a web-based training and educational toolset that provides a quantified score for diagnosticians/users to compare their performance against their peers and view misdiagnosed cells. We have since demonstrated the ability of this platform to quickly train humans without prior training to reach high diagnostic accuracy as compared to expert diagnosticians. Our initial trial group of 55 middle and high school students has collectively played more than 170 hours, each demonstrating significant improvements after only 3 hours of training games, with diagnostic scores that match expert diagnosticians’. Next, through a national-scale educational outreach program in South Korea we recruited >1660 students who demonstrated a similar performance level after 5 hours of training. We plan to further demonstrate this tool’s effectiveness for other diagnostic tasks involving image labeling and aim to provide an easily-accessible and quickly adaptable framework for online training of new diagnosticians.
StressPhone: smartphone based platform for measurement of cortisol for stress detection (Conference Presentation)
Aadhar Jain, Elizabeth Rey, Seoho Lee, et al.
Anxiety disorders are estimated to be the most common mental illness in US affecting around 40 million people and related job stress is estimated to cost US industry up to $300 billion due to lower productivity and absenteeism. A personal diagnostic device which could help identify stressed individuals would therefore be a huge boost for workforce productivity. We are therefore developing a point of care diagnostic device that can be integrated with smartphones or tablets for the measurement of cortisol - a stress related salivary biomarker, which is known to be strongly involved in body's fight-or-flight response to a stressor (physical or mental). The device is based around a competitive lateral flow assay whose results can then be read and quantified through an accessory compatible with the smartphone. In this presentation, we report the development and results of such an assay and the integrated device. We then present the results of a study relating the diurnal patterns of cortisol levels and the alertness of an individual based on the circadian rhythm and sleep patterns of the individual. We hope to use the insight provided by combining the information provided by levels of stress related to chemical biomarkers of the individual with the physical biomarkers to lead to a better informed and optimized activity schedule for maximized work output.
Poster Session
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Melanoma detection using a mobile phone app
Luciano E. Diniz, K. Ennser
Mobile phones have had their processing power greatly increased since their invention a few decades ago. As a direct result of Moore’s Law, this improvement has made available several applications that were impossible before. The aim of this project is to develop a mobile phone app, integrated with its camera coupled to an amplifying lens, to help distinguish melanoma. The proposed device has the capability of processing skin mole images and suggesting, using a score system, if it is a case of melanoma or not. This score system is based on the ABCDE signs of melanoma, and takes into account the area, the perimeter and the colors present in the nevus. It was calibrated and tested using images from the PH2 Dermoscopic Image Database from Pedro Hispano Hospital. The results show that the system created can be useful, with an accuracy of up to 100% for malign cases and 80% for benign cases (including common and atypical moles), when used in the test group.
Shed a light of wireless technology on portable mobile design of NIRS
Yunlong Sun, Ting Li
Mobile internet is growing rapidly driven by high-tech companies including the popular Apple and Google. The wireless mini-NIRS is believed to deserve a great spread future, while there is sparse report on wireless NIRS device and even for the reported wireless NIRS, its wireless design is scarcely presented. Here we focused on the wireless design of NIRS devices. The widely-used wireless communication standards and wireless communication typical solutions were employed into our NIRS design and then compared on communication efficiency, distance, error rate, low-cost, power consumption, and stabilities, based on the requirements of NIRS applications. The properly-performed wireless communication methods matched with the characteristics of NIRS are picked out. Finally, we realized one recommended wireless communication in our NIRS, developed a test platform on wireless NIRS and tested the full properties on wireless communication. This study elaborated the wireless communication methods specified for NIRS and suggested one implementation with one example fully illustrated, which support the future mobile design on NIRS devices.
Potential applications of near infrared auto-fluorescence spectral polarized imaging for assessment of food quality
The current growing of food industry for low production costs and high efficiency needs for maintenance of high-quality standards and assurance of food safety while avoiding liability issues. Quality and safety of food depend on physical (texture, color, tenderness etc.), chemical (fat content, moisture, protein content, pH, etc.), and biological (total bacterial count etc.) features. There is a need for a rapid (less than a few minutes) and accurate detection system in order to optimize quality and assure safety of food. However, the fluorescence ranges for known fluorophores are limited to ultraviolet emission bands, which are not in the tissue near infrared (NIR) “optical window”. Biological tissues excited by far-red or NIR light would exhibit strong emission in spectral range of 650-1,100 nm although no characteristic peaks show the emission from which known fluorophores. The characteristics of the auto-fluorescence emission of different types of tissues were found to be different between different tissue components such as fat, high quality muscle food. In this paper, NIR auto-fluorescence emission from different types of muscle food and fat was measured. The differences of fluorescence intensities of the different types of muscle food and fat emissions were observed. These can be explained by the change of the microscopic structure of physical, chemical, and biological features in meat. The difference of emission intensities of fat and lean meat tissues was applied to monitor food quality and safety using spectral polarized imaging, which can be detect deep depth fat under the muscle food up to several centimeter.
Evaluation of PpIX formation in Cervical Intraepithelial Neoplasia I (CIN) using widefield fluorescence images
Optical techniques has been described as auxiliary technology for screening of neoplasia because shows the potential for tissues differentiation in real-time and it is a noninvasive detection and safe. However, only endogenous fluorophores presents the lesion may be insufficient and needed of the administration of the fluorophores synthesized, such as, precursor molecule of protoporphyrin IX (PpIX) induced by 5- aminolevulinic acid and your derivatives. Topical application of methylaminolevulinate (MAL), induces formation of the endogenous photosensitizer, PpIX in tissues where carcinogenesis has begun. The PpIX tend to accumulate in premalignant and malignant tissues and the illumination with light with appropriate wavelength beginning to excitation of PpIX fluorescence, which helps to localize PpIX-rich areas and identify potentially malignant tissues. The aim of the study is to evaluate the production of PpIX in the cervix with CIN I through of the fluorescence images captured after 1 hour of cream application. It was possible to visualize PpIX fluorescence in cervix and it was possible to observe the selectivity in fluorescence in squamous-columnar junction, which a pre-cancerous condition (CIN) and usually is localized. Through the image processing it was possible to quantify the increase of red fluorescence. For the CIN I the increase of red fluorescence was approximately of 4 times indicating a good PpIX formation.