Projects

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3D Retinal Tissue Bioreactor for Retinal Therapy Development

Retinal degenerative diseases currently have limited treatment options partly due to a lack of effective in vitro model systems to investigate mechanisms of disease pathogenesis and evaluate new therapies. To face this challenge, research has been conducted to culture three-dimensional (3D) retinal organoids from mammalian pluripotent stem cells (PSC).

Retinal Tissue Electrospinning Bioreactor

Adaptive Optics Retinal Imaging with Eye Tracking

The goal of this project with the Clinical and Translational Imaging Unit, NEI, is to design and integrate both closed-loop optical stabilization, using real-time retinal tracking, and image registration into an existing adaptive optics scanning light ophthalmoscope to improve image quality and reduce data loss due to eye motion.

Adaptive Optics Kit from Thorlabs

Analytical Ultracentrifugation Fluorescence Detectors and Acquisition Systems for Protein Assembly Dynamics Studies

Analytical ultracentrifugation, though a classical biophysical discipline, has undergone a renaissance in the last decade due to new computational capabilities and new instrumentation, with increasing applications in structural biology and immunology, for example, for the study of protein interactions and multi-protein complexes, and in biotechnology industry for the characterization of protein pharmaceuticals and nanoparticles for drug delivery. 

Lower speed centrifuge system used for fluorescence detection platform development and AUC analysis of rapid-sedimenting and non-diffusing particles

Drosophila Flight Initiation Detection System

Drosophila is a widely used model organism for neuroscience research.  One topic of interest to neuroscience researchers is the flight ability in Drosophila.  Fruit flies first acquire wings at the end of metamorphosis, when they emerge from the pupal case as adults.  The first activity as adults is to expand and harden their wings, which form as compact folded structures.  Mapping the neural circuitry underlying wing expansion and understanding the interaction, if any, between wing expansion neural circuitry and the circuits regulating flight requires a better understanding when flight abi

Drosophila flight initiation detection system

Electron Paramagnetic Resonance (EPR) Imaging of in-vivo Oxygen Status Associated with Cancer Treatment Studies

In this collaboration, EPR imaging technology is demonstrated to be a novel physiological imaging modality useful in obtaining maps of tissue oxygenation quantitatively and non-invasively with high spatial and temporal resolution. In vivo EPR imaging has been successfully implemented in small animal experiments, specifically in mouse models of human cancer to obtain information (e.g., dynamics of tumor physiology, hypoxia) critical for treatment selection (e.g., chemotherapy, anti-angiogenic drug therapy, and radiotherapy) and response monitoring.

EPR imaging system instrumentation

HAMMS - Hand-Arm Movement Monitoring System

HAMMS was originally conceived by NIDA as a system for pre-symptomatic diagnosis of Parkinson’s disease by monitoring a patient’s fine locomotor abilities. SPIS designed HAMMS to be a clinic-friendly (i.e., low cost, portable, and quick routine diagnostic) system consisting of a camera and custom video processing algorithm.  The system tracks the hand of a patient performing a set of motions as defined by a path outlined on a computer screen, and also provides visual feedback (i.e., real-time machine vision) to the participant as to how well they are maintaining the desired path.

Photo of HAMMS system in use

Hematoma Detector - A Practical Application of Instrumental Motion as Signal in Near Infra-Red Imaging

Functional neuroimaging, particularly functional MRI (fMRI) which provides a measure of regional brain blood flow during behavior, is widely used in the investigation of cognitive processes and has been proposed as a means of evaluating deficits due to traumatic brain injury (TBI) and guiding rehabilitation.

Test setup for prototype hematoma detector system

High-resolution Gamma Imager for Small Animal Imaging of Radioisotopes for Cancer Treatment

SPIS collaborated with NCI’s Molecular Imaging Program (MIP) to develop novel imaging systems used in the development of radionuclide-labeled compounds. Successfully developed radionuclide-labeled compounds offer the ultimate prospect of PET, SPECT and planar imaging in human subjects for medical diagnostic and management purposes.  Equally powerful applications exist in basic science when used for probe validation in small laboratory animals.

MONICA detector module and electronics

Illumination Control System for Mouse Visual Cycle Studies

The goal of this project is to enable light stress experiments at chronic light exposure duration on transgenic mice harboring knockin mutations in the RPE65 gene.

Image of System in NEI Animal Facility

Image-Based Robotic Targeting System to Control Micromanipulators for Single Cell Studies in Living Biological Tissues

We are developing a second-generation software system for image-based robotic automation of micromanipulators, which entails seamless integration and control of combined optical-mechanical systems used for NINDS biological investigation.

3D model of micromanipulator and micropipette

Large Scale Sensor-based System for Mouse Cage Environment Monitoring (MIOS)

Rodents are used in large numbers at research institutions aiming to understand mechanisms of disease and develop new therapies. To assess a research hypothesis or treatment efficacy, for example, the behavior and welfare of the animal must be monitored. Traditional methods for behavior assessment rely on trained staff specialists performing daily checks of each cage.  Given the large number of cages housed in each institution, these manual checks are laborious and susceptible to bias.

MIOS

mHealth Smartphone Application to Measure Risky Driving Behavior and Predict Crashes

The risk of fatal crashes per driven mile is highest among teen drivers compared to other age groups. According to the CDC statistics only in 2014, 221,313 teens drivers were admitted to the emergency department and 2,333 were killed. This amounts to an average of six teen driver deaths every day due to automotive crashes. Improved safety policies are known to reduce the number of motor vehicle crashes among teens.

mHealth Smartphone Application to Measure Risky Driving Behavior

Microfabricated Polymeric Vessel Mimetics for Cancer Cell Culture

Studies evaluating potential chemotherapeutics and multi-drug resistance in cancer cells have been established using in vitro 2D culture and in vivo animal models. However, neither method accurately recapitulates human tissue or the course of tumorigenesis. 3D cell cultures better simulate the in vivo environment for tumor growth, but is currently limited by insufficient mass transport of oxygen due to a lack of vasculature.

Hypoxia Chamber Bioreactor

Multiparametric MRI in Localization of Prostate Cancer with Patient-specific MRI-based Prostate Mold Validation

The NCI Molecular Imaging Program develops innovative methods of localizing prostate cancer based on in vivo multiparametric MRI.  SPIS contributes to this effort in two areas.  (1) Assisted in the design, implementation, and validation of individualized MR-based molds to facilitate the correlation of the multiparametric MRI imaging with downstream histopathology.  Achieving sufficient MR/histopathology image correlation (i.e., 3D alignment) is critical when evaluating the efficacy of new prostate imaging protocols as potential cancer diagnostics.  During the initial mold developme

Patient-specific 3D printed Mold

Non-Injurious Pain Model Using Mice

Patients cite pain as the most common reason for seeking health care, and some medical organizations include pain as a fifth vital sign along with blood pressure, heart rate, temperature, and respirations. While the understanding of the neurophysiologic mechanisms by which noxious and non-noxious stimuli are perceived has substantially improved, the mechanisms of pain are not entirely understood.

Graphic demonstrating Neurometer connection to mouse

Noninvasive Multispectral Imaging to Quantitatively Assess Tissue Vasculature

SPIS collaborated with the NICHD Program in Physical Biology to develop a clinical multispectral imaging system.  The instrument acquires images of the target area in up to six different spectral bands (700 nm, 750 nm, 800 nm, 850 nm, 900 nm, and 1000 nm).  Images at these wavelengths are input into both a mathematical optical skin model and a reconstruction algorithm to quantify the percent of blood in a given area, as well as the percent of blood that is oxygenated in the tissue and surrounding vasculature.  The methodology has been applied to assess vascular Kaposi’s sarcoma lesions and

Multispectral imaging system clinical prototype

Portable Fluorescence Camera System for Offsite Ovarian Tumor Imaging

In collaboration with the NCI Molecular Imaging Program (MIP), SPIS designed and implemented a novel portable fluorescence imaging system which has proven to be a valuable asset in the clinical translation of molecular imaging probes. Molecular imaging probes allow surgeons and endoscopists to visualize tumor tissue which normally would not be visible to the naked eye.

3D rendering of portable fluorescence camera system

PRiME - Physiological Recording in MRI Environment

A multidisciplinary intramural team led by CIT in collaboration with the NHLBI Cardiovascular Intervention Program developed and implemented a fundamental electronics and signal processing tool facilitating MRI catheterization procedure innovation.  As an alternative to surgical techniques in the treatment of cardiovascular disease, NHLBI is developing innovative techniques in cardiovascular catheterization with the use of real-time MRI. The use of MRI greatly reduces the patient’s exposure to ionizing radiation from X-ray imaging, which is typically used in catheterization procedures.

PRiME reduces MRI-induced noise in ECG and IBP signals

Quantitative Fluorescence Lifetime Imaging for Disease Detection and Monitoring

SPIS collaborated with the NICHD Program in Physical Biology to develop a Lifetime Fluorescence Imaging system.  With certain fluorophores, the fluorescence emission lifetime changes in response to changes in the immediate tissue environment.  This instrument was developed to quantify these changes in lifetime to investigate whether this method could be used as an effective non-invasive early-stage tumor detection system.  SPIS was responsible for instrumentation hardware specification and integration.  SPIS also developed the software for instrument control and data acquisition.  The instr

Custom software user interface for Lifetime Fluorescence Imaging system

SCORHE: System for Continuous Observation of Rodents in Home-cage Environment

In collaboration with NCI, NIDDK, NIMH, and FDA, SCORHE is designed to meet the demands of NIH IRP researchers and animal care staff to automatically assess laboratory mice ethology in large-scale settings. SCORHE is comprised of custom video-acquisition and analysis tools developed to quantify mice activity and behavior for short and long (multi-day) durations while housed within a typical home-cage. The specialized hardware was designed to be space efficient, compatible with vivarium cage racks, and animal-facility user friendly.

SCORHE 3D CAD and prototype in ventilated rack

System to Measure Rodent Vestibular Sensory Evoked Potentials

The Mouse Auditory Testing Core within NIDCD provides investigators with assistance in testing auditory function in rodents. In addition to the standard auditory testing (such as auditory brainstem response), NIDCD is expanding core capabilities to include the often needed testing of vestibular sensory evoked potentials (VsEPs). VsEPs are used to assess the vestibular system, which is a critical component associated with a sense of balance.

3D model of the custom mouse head clip and mounting hardware for the VsEPs system

Technologies for Neuronal Mapping of Motion Detection and Color Vision Systems of Drosophila

SPIS has been collaborating with NICHD's section on neuronal connectivity and NIBIB to develop one-of-kind virtual-reality (VR) behavioral systems to assess the functions of Drosophila visual circuits. These VR systems are comprised of custom electronics, opto-electronics, imaging systems, mechanical hardware, and software. Since vertebrates share similar visual functions and neural circuit architectures, the research will provide a better understanding of how these systems receive, process, and interpret visual stimuli associated with motion and color.

VR motion detection prototype system

Tissue MicroArrayer for High Throughput Analysis of Pathology Tissue Samples

NIH researchers introduced an innovative technique for high density arraying of archival clinical tissue in the research and clinical laboratory. Consisting of an array of cylindrical cores extracted from formalin-fixed paraffin embedded tissue samples, tissue microarrays (TMA) have become widely used as a powerful validation tool for high throughput genomic screens.

Automated robotic tissue microarrayer

Tissue Microdissection for Molecular Analysis of Disease States and Normal Development – Target Activated Microdissection (TAM)

Laser Capture Microdissection (LCM) is a well-established technology used to isolate cells of interest from surrounding tissue cells on a microscope slide. As early co-inventors of LCM in the mid-90s, SPIS staff have continued to develop innovative tissue microdissection technologies, working with partners in NCI, NICHD, NIBIB, NIMH, NIDA, and industry.  Although LCM is already commercially successful, the method requires a skilled operator to select the cells for capture, which leads to operator variability and limits overall throughput.

Internal components of fTAM device

Two-Photon Excitation Fluorescence Microscopy Motion Tracking to Study in-vivo Subcellular Structures

SPIS collaborated with the NHLBI Laboratory of Cardiac Energetics to develop a methodology enabling the study in vivo sub-cellular structures and signaling processes in real-time.  Multi-photon fluorescence imaging provides improved tissue penetration, sensitivity, and information content when investigating dynamic intercellular events within living tissue, but physiological motion degrades the quality of these images and makes temporal observations challenging.  Our system implementation, designed to be functional in tandem with the commercial two-photon microscope system, adjusts

Time-lapse volume of with and without motion tracking correction

Using Autonomic Responses to Infer Emotional State

Emotions play an important role in decision making. Emotions also influence our autonomic nervous system presumably through the amygdala and other regions of the brain. It has been hypothesized that feedback from autonomic nervous activity enhances learning and decision making. Well-learnt associations are used to predict or anticipate outcomes of related events, thereby increasing the chances of making a correct decision and ultimately increasing the deciding organism’s chances of survival.

Visualization of learning task

Video Analysis System for Behavior and Activity Assessment of Fruit Flies in High-Throughput Studies

Over the past decade, there has been a growing interest in the development of monitoring devices and automated systems for detecting behavioral changes in D. melanogaster in response to different stimuli, aiming to reduce the cost and duration of standard assays.

3D CAD of MUFFIN unit

Virtual Reality System for the Study of Neural Processes Underlying Self-Agency

For voluntary motor control to occur, normal individuals must have a sense of ownership over the effector (i.e. their hand in a voluntary grasp), and a sense of agency (i.e. the hand movement was initiated by them). In cases such as orticobasal degeneration, alien limb syndrome, and various other psychogenic movement disorders, patients experience various movements which they judge to be involuntary, or performed by an outside agent (referred to as passivity phenomenon in the setting of schizophrenia and manifests as auditory or visual hallucinations).

Demonstration of virtual reality paradigm

Visible and IR Optical Scanning Spectrometry To Study Energy Transduction by Bacteriorhodopsin

Energy-driven proton pumps are of major importance for energy-transduction in living systems. The respiratory chain of animals, as well as single cellular organisms, uses energy released from electron transport to oxygen to form an electrochemical gradient for protons, which is then used to synthesize ATP, a critical element in intracellular energy transfer.

Custom printed circuit boards designed by SPIS