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Patent
Inscopix, Inc. | Date: 2016-09-02

Provided herein are systems and methods for multi-color imaging using a microscope system. The microscope system can have a relatively small size compared to an average microscope system. The microscope system can comprise various components configured to reduce or eliminate image artifacts such as chromatic aberrations and/or noise from stray light that can occur during multi-color imaging. The components can be configured to reduce or eliminate the image artifacts, and/or noise without substantially changing the size of the microscope system.


Jennings J.H.,University of North Carolina at Chapel Hill | Ung R.L.,University of North Carolina at Chapel Hill | Resendez S.L.,University of North Carolina at Chapel Hill | Stamatakis A.M.,University of North Carolina at Chapel Hill | And 10 more authors.
Cell | Year: 2015

Optimally orchestrating complex behavioral states, such as the pursuit and consumption of food, is critical for an organism's survival. The lateral hypothalamus (LH) is a neuroanatomical region essential for appetitive and consummatory behaviors, but whether individual neurons within the LH differentially contribute to these interconnected processes is unknown. Here, we show that selective optogenetic stimulation of a molecularly defined subset of LH GABAergic (Vgat-expressing) neurons enhances both appetitive and consummatory behaviors, whereas genetic ablation of these neurons reduced these phenotypes. Furthermore, this targeted LH subpopulation is distinct from cells containing the feeding-related neuropeptides, melanin-concentrating hormone (MCH), and orexin (Orx). Employing in vivo calcium imaging in freely behaving mice to record activity dynamics from hundreds of cells, we identified individual LH GABAergic neurons that preferentially encode aspects of either appetitive or consummatory behaviors, but rarely both. These tightly regulated, yet highly intertwined, behavioral processes are thus dissociable at the cellular level. © 2015 Elsevier Inc.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 726.19K | Year: 2016

Project Summary There is increasing awareness that aberrant neural circuit activity is a core manifestation of many neuropsychiatric diseases including autism schizophrenia depression and Alzheimerandapos s disease This realization has opened tantalizing prospects for more powerful and precise therapeutic approaches based on retuning of abnormal circuit activity However we still lack crucial understanding of neural activity patterns during normal behavior and how these patterns are altered in disease Many rodent models of human brain diseases are now available but neuroscientists are still hindered by lack of a technology for visualizing activity in large populations of genetically identified neurons in the brains of behaving animal subjects Inscopix Inc spun out of Stanford University to commercialize a miniature fluorescence microscope technology that lets neuroscientists visualize Ca dynamics in up to neurons simultaneously in awake behaving rodents at cellular resolution The microscope is easily carried on the head of a mouse or rat and enables continuous recording from the same group of neurons in a single animal for periods of days to weeks Used in conjunction with genetically encoded Ca indicators and our custom designed optical microendoscope probes the microscope enables targeting of predefined neuronal subpopulations and entry to brain regions inaccessible to other large scale recording technologies In Phase I we developed and validated a new version of the microscope that is substantially higher performing and more robust than the original Stanford prototype Around it we built the nVista imaging system an end to end solution for in vivo brain imaging that includes the miniature microscope with an integrated HD camera and electronics and user friendly data acquisition hardware and software The nVista system has now been disseminated for beta testing to over labs around the globe This Phase II project will move the nVista system forward in its next steps towards marketing to the general neuroscience community through the following aims Create a next generation version of the nVista system for commercial dissemination Making use of feedback from early adopters we will refine the systemandapos s design for greater performance reliability and ease of use by incorporating an electronic focusing mechanism enabling higher speed data acquisition and seamless interfacing with other data collection systems Extend the technology to rats by developing an accessory array for the nVista microscope that includes a new base plate attachment mechanism protective head mounted cone and cable sheathing optical probes and an optical data link to support commutators and Develop a next generation data analysis platform with faster processing customizability and better visualization tools Project Narrative This grant will further develop and refine a revolutionary miniature microscope technology to observe and investigate the thinking working brain in animal subjects at the level of its neural circuits populations of brain cells that control specific functions The technology we develop and ready for future commercialization has the potential to transform our understanding of how the brain works in health and how it malfunctions in human brain disorders including psychiatric disorders that involve abnormalities in large scale brain function such as schizophrenia depression attention deficit disorder and autism


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 689.77K | Year: 2012

DESCRIPTION (provided by applicant): There is a rising emphasis today on the role of neural circuitry in neuropsychiatric disease. However we still lack crucial knowledge of both normal patterns of neural activity and how these patterns go awry in disease.Although brain researchers have already created mouse models of many human brain diseases, presently there is no technology that can visualize the activity of large numbers of individual, neurons of genetically identified types in the brains of behaving mice - ideally in multiple mice in parallel. The capacity to obtain such large-scale data sets is important towards identifying neurophysiologic signatures of brain disease and is a prerequisite for developing therapeutic means of re-tuning aberrant activity patterns. Fluorescence microscopy has key advantages for tracking neural activity. However, while conventional fluorescence microscopes offer the spatiotemporal resolution needed for imaging the brain's cellular dynamics, they neither permit studies infreely behaving mice nor are scalable for studies of large numbers of animal subjects. If fluorescence microscopes could be made small, portable, and cheap, then in principle large numbers of behaving mice could be studied in parallel. Inscopix, Inc. hasspun-out of Stanford University to commercialize miniature, integrated fluorescence microscopes - imaging technology that helps neuroscientists visualize neural circuit dynamics in awake behaving mice and rats. Prototype microscopes at Stanford are already enabling imaging of cerebellar microcirculation and permitting visualization of Ca2+ dynamics within hundreds of individual neurons (over weeks in some experiments) as the animal behaves freely in a naturalistic manner. The core miniature, integrated microscope technological innovation and its promise for studying the brain and its diseases was recently featured in Nature, MIT Technology Review, and several media outlets. In Phase I Inscopix aims to develop and test a new set of prototype microscopes that are significantly higher-performing, robust and part of a user-friendly end-to-end solution for in vivo brain imaging in freely behaving rodents. Specifically, we will: (1) Desig and create a new version of our miniaturized, integrated microscope. We will further develop the core technology and incorporate several improvements to significantly enhance imaging performance and extend the capabilities for in vivo brain imaging, including: (a) Attaining spatial resolution finer than 1 m over fields-of-viewup to 1 mm2; (b) Developing a digital, high-speed rotary commutator enabling unsupervised, imaging studies of brain activity; (c) Creating a robust and reliable microscope housing suitable for low-cost manufacturing in large volumes. (2) Develop accompanying hardware and software for data acquisition and processing. We will create a compact and user-friendly USB-compatible box for image acquisition and microscope control along with an easy-to-use Graphical User Interface (GUI). (3) Fabricate and test 10 newminiature microscopes with accompanying peripherals. We will fabricate and internally test our new designs before distributing 10 prototypes to carefully chosen beta labs for in vivo testing and validation. By the end of Phase I we expect to have receivedconsiderable in vivo usage feedback from beta labs, laying the foundation for volume production and roll-out of a market-ready product in Phase II. PUBLIC HEALTH RELEVANCE: Modern understanding of brain disease is currently undergoing a sea change, gradually shifting away from theories that emphasize a dearth or excess of neurotransmitter, and towards more sophisticated theories in which neurons of specific types exhibit improper patterns of ensemble activity underlying aberrant human behavior. This shift is especially important for disorders such as autism, which defy simple neurochemical explanations and appear to arise from circuit-level abnormalities; for disorders for which there has been much evidence to support roles for altered neurochemistry, such as schizophrenia or depression, there is rising appreciation for the equally important roles of pathologic neural circuit dynamics in causing disease phenotypes. Inscopix will develop and commercialize an innovative imaging technology for visualizing neural activity in behaving mice - and in principle, across large numbers of subjects in parallel - helping researchers obtain some of the missing knowledge about normal and aberrant neural activity patterns in mouse models of human brain disease, a key step towards developing novel therapeutics and corrective strategies.


Trademark
Inscopix, Inc. | Date: 2016-08-19

digital microscope equipment, namely, couplers; digital microscope lens probes.


Trademark
Inscopix, Inc. | Date: 2016-08-22

digital microscopes; digital microscope equipment, namely, couplers; digital microscope lens probes; computer hardware for processing images and video; computer software for viewing, recording, saving, and analyzing images and video.


Patent
Inscopix, Inc. | Date: 2013-02-14

Systems and methods are provided for imaging a sample. A portable slide reader may be provided that may be configured to accept a slide and that may contain one or more miniature microscopes therein. The slide reader may include a display showing images captured by the microscopes. The slide may be movable relative to the microscopes and the position of the captured image may be controllable. In some instances, images captured may be useful for DNA sequencing. Multiple color ranges may be captured for a target region, corresponding to different nucleobases.


Patent
Inscopix, Inc. | Date: 2013-02-07

System and methods are provided for distributed microscopy. A plurality of microscopes may capture images and send them to a media server. The microscopes and the media server may be part of a local area network. The microscopes may each have a distinct network address. The media server may communicate with an operations console, which may be used to view images captured by the microscopes. The operations console may also accept user input which may be used to selectively control the microscopes.


Patent
Inscopix, Inc. | Date: 2013-11-05

The invention provides miniaturized devices, systems and methods for imaging of biological specimens. The devices and system provide accurate alignment and modular mounting of imaging components internally and in relation to the target subject. In some embodiments, the invention provides devices, systems and methods for in vivo fluorescent brain imaging in freely-behaving rodents.


PALO ALTO, Calif.--(BUSINESS WIRE)--Inscopix, Inc. today announced it ranked number 61 on Deloitte’s Technology Fast 500™, a ranking of the 500 fastest growing technology, media, telecommunications, life sciences and energy tech companies in North America. Inscopix’s chief executive officer, Kunal Ghosh credits its scientists with the company’s revenue growth. He said, "Inscopix is honored to be recognized as one of the fastest growing companies in North America. Our growth is thanks to our val

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