Electrophysiology and Multiphoton Imaging Rigs

Federal Business Opportunities (FBO)SOURCES SOUGHT NOTICE1. Solicitation Number: NIH-NIDA-NINDS-19-0034492. Title: Electrophysiology and multiphoton imaging rigs3. Classification Code: 66 - Instruments & laboratory equipment4. NAICS Code: 3339995. Description: Electrophysiology and multiphoton imaging rigsThis is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist

the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice.This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only.Background: The National Institute of Neurological Disorders and Stroke (NINDS) is establishing a new laboratory that will use cutting-edge physiological, imaging, and behavioral methods to investigate the relationship between human neurological disorders and brain function at the molecular, synaptic, cellular, and circuit levels. The new laboratory requires several systems, including complete rigs for brain slice electrophysiology and multiphoton imaging (both in vitro and in vivo). Given the complexity of the planned experiments, systems that integrate tightly with each other are required.Purpose and Objectives: The NINDS will soon establish the Laboratory of Circuits, Synapses, and Molecular Signaling (LCSMS), which will be led by the new Scientific Director. The LCSMS will study fundamental issues of synaptic transmission, neuronal excitability, neuromodulation, and neural circuit activity using animal models (principally, the mouse). These issues will be related to human neurological disorders, such as Alzheimer's and other neurodegenerative disorders, and will be explored in brain areas including (but not limited to) the amygdala, basal forebrain cholinergic areas, the ventral hippocampus, and the prefrontal cortex.1. Project requirements: Salient CharacteristicsA major line of research will employ patch clamp electrophysiology, multiphoton imaging, and virtual reality. This research requires four systems that must be tightly integrated with each other: (1) a rig capable of multipatch recording from cell bodies and dendritic structures in brain slices, imaging of fluorescently-tagged neurons and dendrites, and simultaneous widefield photoactivation (i.e., optogenetic stimulation or neurotransmitter uncaging); (2) a rig with these same capabilities plus laser-based components for focal and patterned photoactivation; (3) a rig capable of simultaneous multiphoton microscopy, photoactivation, and multipatch recording in brain slices; and (4) a rig capable of simultaneous multiphoton microscopy and photoactivation that can be used with an awake, head-fixed mouse walking on a treadmill or floating ball and that can accommodate a virtual reality environment made up of several large thin-film-transistor (TFT) liquid crystal displays.The four systems shall be tightly integrated with each other and allow for components to be swapped between them for maximum flexibility in experimental design. The need for integration and component swapping is explained further in the last part of the Salient Characteristics section.These four complete electrophysiology and/or multiphoton imaging systems should have the capabilities listed in the following table where Y = Yes and N = No.Rig 1 Rig 2 Rig 3 Rig 4Brain slice electrophysiology Y Y Y NLED optogenetic stimulation Y Y N NLaser optogenetic stimulation N Y Y YMultiphoton imaging on brain slices N N Y NMultiphoton imaging with awake mice N N N YUsed in conjunction with virtual reality N N N Y.The four systems are specified in more detail in the next four subsections. A description of the need for integration and component swapping between the systems immediately follows.RIG 1: PATCH CLAMP ELECTROPHYSIOLOGYOne patch clamp electrophysiology system with tight, computer-controlled integration between the microscope, stage, and manipulator elements.• Include at least four micromanipulators capable of patch clamp recording from structures as small as the dendrites of mouse neocortical neurons. The micromanipulators must have a travel distance in every direction of at least 20 mm, a spatial resolution of 20 nm, and a drift of no more than 1 micron over two hours. It should be possible to expand the number of micromanipulators to six, with independent pipette exchange on all six. It should be possible to transform micromanipulators from a right-hand configuration to a left-hand configuration. It should be possible to link movement along the X and Z axes so that electrodes move diagonally along a virtual 4th axis at a user-specified angle.• An upright microscope equipped with infrared-differential interference contrast (IR-DIC) optics (for visualized patch recording in brain slices as thick as 400 microns) and epifluorescence equipment (for all widely-used fluorophores, including GFP, mCherry, tdTomato). The microscope should have motorized condenser and objective arms to allow for remote control, including through computer software. Must include 4x and 40x objectives.• A motorized XY stage that can be controlled by computer software.• Tight integration between microscope, micromanipulators, and stage is required for the complex experiments planned for the LCSMS. The Contractor must provide a software package that allows users, through a graphical user interface (GUI), to control all three and coordinate their movement for the sake of multipatch recording. The software package must be compatible with the Windows 10 (64 bit) operating system.• A CCD camera suitable for both IR-DIC (visualized patch) and fluorescence (identification of fluorescently-tagged structures) imaging. A frame rate of at least 20 fps and at least 14-bit resolution are required. The camera should connect to a computer via a USB 3.0 interface and include imaging software.• A platform and chamber for brain slices.• A low-noise temperature controller for bath salines.• A perfusion pump for bath salines.• An anti-vibration table with Faraday cage. The table must be no larger than 30 inches by 36 inches.• Patch clamp amplifiers suitable for both current clamp and voltage clamp recordings. At least four channels of amplification must be available. The amplifiers must have built-in circuitry for standard electrophysiological compensation modes (e.g., bridge balance, fast and slow pipette capacitance compensation, series resistance compensation). The amplifiers must be computer-controlled and should interface with open-source electrophysiology software written in a widely-used language such as Matlab, LabView, or Python. Matlab is the preferred language.RIG 2: PATCH CLAMP ELECTROPHYSIOLOGY (WITH LASER STIMULATION)One patch clamp electrophysiology system with tight, computer-controlled integration between the microscope, stage, and manipulator elements. This system must include a laser-based subsystem for focal and patterned optogenetic stimulation.• Include at least four micromanipulators capable of patch clamp recording from structures as small as the dendrites of mouse neocortical neurons. The micromanipulators must have a travel distance in every direction of at least 20 mm, a spatial resolution of 20 nm, and a drift of no more than 1 micron over two hours. It should be possible to expand the number of micromanipulators to six, with independent pipette exchange on all six. It should be possible to transform micromanipulators from a right-hand configuration to a left-hand configuration. It should be possible to link movement along the X and Z axes so that electrodes move diagonally along a virtual 4th axis at a user-specified angle.• An upright microscope equipped with infrared-differential interference contrast (IR-DIC) optics (for visualized patch recording in brain slices as thick as 400 microns) and epifluorescence equipment (for all widely-used fluorophores, including GFP, mCherry, tdTomato). The microscope should have motorized condenser and objective arms to allow for remote control, including through computer software. Must include 4x and 40x objectives.• A motorized XY stage that can be controlled by computer software.• Tight integration between microscope, micromanipulators, and stage is required for the complex experiments planned for the LCSMS. The Contractor must provide a software package that allows users, through a graphical user interface (GUI), to control all three and coordinate their movement for the sake of multipatch recording. The software package must be compatible with the Windows 10 (64 bit) operating system.• A CCD camera suitable for both IR-DIC (visualized patch) and fluorescence (identification of fluorescently-tagged structures) imaging. A frame rate of at least 20 fps and at least 14-bit resolution are required. The camera should connect to a computer via a USB 3.0 interface and include imaging software.• A platform and chamber for brain slices.• A low-noise temperature controller for bath salines.• A perfusion pump for bath salines.• An anti-vibration table with Faraday cage. The table must be no larger than 36 inches by 48 inches.• Patch clamp amplifiers suitable for both current clamp and voltage clamp recordings. At least four channels of amplification must be available. The amplifiers must have built-in circuitry for standard electrophysiological compensation modes (e.g., bridge balance, fast and slow pipette capacitance compensation, series resistance compensation). The amplifiers must be computer-controlled and should interface with open-source electrophysiology software written in a widely-used language such as Matlab, LabView, or Python. Matlab is the preferred language.• Include components for laser-based optogenetic stimulation or neurotransmitter uncaging. The components must include a galvanometer-based method for quickly and reliably positioning the laser beam. A software package must be provided allowing users to determine stimulation pattern and settings using a GUI. The components must allow for stimulation/uncaging at commonly-used wavelengths - namely, those for channelrhodpsin, halorhodopsin, and caged glutamate.RIG 3: MULTIPHOTON IMAGING ON BRAIN SLICESOne system capable of simultaneously performing and integrating three functions: (A) multiphoton imaging, (B) optogenetic stimulation or neurotransmitter uncaging (i.e., photoactivation), and (C) patch clamp electrophysiology from multiple neuronal structures within brain slices.The system will be installed, together with a second multiphoton system, on a 5' x 10' anti-vibration table in Building 35A. The table will be in a room formed by combining the present rooms 3B-415 and 3B-214; the new room will have the dimensions 14 feet 4 ¾ inches x 15 feet 7 inches. The table will also house two lasers, which together with associated optical components, will take up approximately 20 square feet of table space and a virtual reality system, which will take up 10 square feet of table space. There will be an equipment cage (approximately 3' x 8') mounted above the air table. The room will be devoted to these two multiphoton systems. Given these table/room characteristics: the following size limitations apply to Rig 3: (1) the system should require no more than 10 square feet of anti-vibration table space; (2) the system should require no more than 12 square feet of the overhead cage space; and (3) all other associated electronics should fit in a relay rack no wider than 26" and no taller than 8'. Both Rig 3 and Rig 4 (described below), including all associated lasers and electronic/optical components, must fit in the designated room.(A) Multiphoton Imaging• The microscope must be able to manipulate two light paths in order to make possible simultaneous two-photon imaging and photoactivation.• The system must allow users to choose between these scanning configurations for the imaging path: galvo/galvo, resonant/galvo, and resonant/galvo/galvo.• The lenses of the scanhead must allow transmission between 700 nm and 1400 nm.• The system must have some means of reducing sound noise (to below 20 dB SPL at a distance of 5'). Although the system will be used with brain slices, the room in which it will be housed will also host experiments on awake behaving mice. Minimizing sound is crucial.• Scanning in the Z direction should have a minimum step size no larger than 0.1 microns.• The system will share two tunable lasers with a second multiphoton system installed on the same anti-vibration table. Systems that cannot do this are not acceptable.• The system should therefore be compatible with Matlab-based control software, such as ScanImage (Janelia).• The multiphoton microscope will be used immediately for experiments on brain slices, but the LCSMS may decide at some point to modify it for use with awake, head-fixed mice. It should be possible to simply convert the multiphoton microscope to an in vivo configuration.(B) Photoactivation• The system will be used for simultaneous two-photon imaging and photoactivation (i.e., optogenetic stimulation or neurotransmitter uncaging). The system should therefore be able to manipulate a second laser beam for this purpose.• Software - ideally, Matlab-based - must be provided for this purpose. This software must allow users to determine scanning pattern using a graphical user interface (GUI).• Arbitrary patterns of stimulation (e.g., spirals, zig-zags, squares, arbitrary shapes) must be possible through the provided software.(C) Electrophysiology• Include at least four micromanipulators capable of patch clamp recording from structures as small as the dendrites of mouse neocortical neurons. The micromanipulators must have a travel distance in every direction of at least 20 mm, a spatial resolution of 20 nm, and a drift of no more than 1 micron over two hours. It should be possible to easily transform micromanipulators from a right-hand configuration to a left-hand configuration. It should be possible to link movement along the X and Z axes so that electrodes move diagonally along a virtual 4th axis at a user-specified angle.• Tight integration between microscope and micromanipulators is required for the complex experiments planned for the LCSMS. The Contractor must provide a software package that allows users, through a graphical user interface (GUI), to control all them and coordinate their movement for the sake of multipatch recording. The software package must be compatible with the Windows 10 (64 bit) operating system.• A platform and chamber for brain slices.• A low-noise temperature controller for bath salines.• A perfusion pump for bath salines.• Patch clamp amplifiers suitable for both current clamp and voltage clamp recordings. At least four channels of amplification must be available. The amplifiers must have built-in circuitry for standard electrophysiological compensation modes (e.g., bridge balance, fast and slow pipette capacitance compensation, series resistance compensation). The amplifiers must be computer-controlled and should interface with open-source electrophysiology software written in Matlab.RIG 4: MULTIPHOTON IMAGING WITH AWAKE MICEOne system capable of simultaneously performing and integrating two functions: (A) multiphoton imaging and (B) optogenetic stimulation or neurotransmitter uncaging (i.e., photoactivation). The system will be used to study neural circuits in a head-fixed but awake mouse sitting on a floating spherical ball or a treadmill and navigating through a virtual reality space (created by large video displays in the mouse's field of view). (C) The microscope must be able to accommodate both the ball/treadmill and the virtual reality displays.The system will be installed, together with a second multiphoton system, on a 5' x 10' anti-vibration table in Building 35A. The table will be in a room formed by combining the present rooms 3B-415 and 3B-214; the new room will have the dimensions 14 feet 4 ¾ inches x 15 feet 7 inches. The table will also house two lasers, which together with associated optical components, will take up approximately 20 square feet of space and a virtual reality system, which will take up 10 square feet of space. There will be an equipment cage (approximately 3' x 8') mounted above the air table. The room will be devoted to these two multiphoton systems. Given these table/room characteristics: the following size limitations apply to Rig 4: (1) the system should require no more than 10 square feet of anti-vibration table space; (2) the system should require no more than 12 square feet of the overhead cage space; and (3) all other associated electronics should fit in a relay rack no wider than 26" and no taller than 8'. Both Rig 3 (described above) and Rig 4, including all associated lasers and electronic/optical components, must fit in the designated room.(A) Multiphoton Imaging• The microscope must be able to manipulate two light paths in order to make possible simultaneous two-photon imaging and photoactivation.• The system must allow users to choose between these scanning configurations for the imaging path: galvo/galvo, resonant/galvo, and resonant/galvo/galvo.• The lenses of the scanhead must allow transmission between 700 nm and 1400 nm.• The system will be used with awake behaving mice and must have some means of reducing sound noise (to below 20 dB SPL). Minimizing sound is crucial.• Scanning in the Z direction should have a minimum step size no larger than 0.1 microns.• The system will share two tunable lasers with a second multiphoton system installed on the same anti-vibration table. Systems that cannot do this are not acceptable.• The system should therefore be compatible with Matlab-based control software, such as ScanImage (Janelia).• The multiphoton microscope will be used immediately for experiments on awake mice, but the LCSMS may decide at some point to modify it for use on brain slices. It should be possible to simply convert the multiphoton microscope to an in vitro configuration.(B) Photoactivation• The system will be used for simultaneous two-photon imaging and photoactivation (i.e., optogenetic stimulation or neurotransmitter uncaging). The system should therefore be able to manipulate a second laser beam for this purpose.• Software - ideally, Matlab-based - must be provided for this purpose. This software must allow users to determine scanning pattern using a graphical user interface (GUI).• Arbitrary patterns of stimulation (e.g., spirals, zig-zags, squares, arbitrary shapes) must be possible through the provided software.(C) Virtual RealityIn this document, the term "virtual reality" refers to systems that use interactive, computer-generated manipulations of sensory experience to create brain states or provoke behavioral responses mimicking those corresponding to the physical environments being simulated on the computer. A broad review of contemporary efforts is given by Thurley and Ayaz, Curr. Zool. 63:109-119 (2017). For the planned experiments of the LCSMS, the virtual reality environment will be created by 6 liquid crystal displays (approximately 19" diagonal and 17" height) arranged so that each display is approximately 15" from the microscope's light path and the displays together wrap around to encompass 270⁰ of the view in the XY plane.• To accommodate a "mouse-sized" spherical running ball, the minimum distance between the bottom of the objective and the anti-vibration table must be no smaller than 10 inches. Likewise, it should be possible to extend the distance between the light path and the microscope frame to at least 8 inches.• In some cases, it would be useful to tilt the objective away from the vertical axis in order to image more lateral parts of the mouse brain. The microscope should accommodate this need.• The system will be used in conjunction with a virtual reality system consisting of several video displays. (A prominent commercial example is the Virtual Reality JetBall built by Phenosys and distributed in North America by Blackrock Microsystems.) The microscope system must be compatible with such virtual reality equipment.INTEGRATION AND COMPONENT SWAPPINGIn each of the four cases (Rigs 1-4), a complete system is desired because of the complexity of the planned experiments. It is imperative that every piece of equipment (manipulators, microscope, XY stage, lasers, LEDs, amplifiers) works well with all the other parts. It is also very important that a unified software package be available to aid in this integration.The four systems are presented together in a single purchase description because they must be integrated together in terms of (A) hardware and (B) user experience (especially software) and (C) because the LCSMS wishes to maximize flexibility in its experimental planning by allowing components to be swapped from one rig to another.• INTEGRATION (hardware)Rigs 3 and 4 will share two tunable lasers. One laser will provide the laser beam for multiphoton imaging while the other laser will provide the laser beam for optogenetic stimulation. This will be true - simultaneously - for both rigs. For laser sharing to work, the two rigs must be tightly integrated with each other, both to accommodate the two lasers and to coordinate their use.• INTEGRATION (user experience)Members of the LCSMS may be required, depending on scientific need, to switch between various types of experiments: in vitro physiology, in vitro physiology with laser stimulation, in vitro physiology with multiphoton imaging, multiphoton imaging in vivo. For such switching to work seamlessly, the rigs must contain compatible hardware (particularly the manipulators) and be run by the same software (at present, the LCSMS anticipates a complete Matlab-based suite of software).• COMPONENT-SWAPPINGThe four rigs have overlapping capabilities. Depending upon future experimental needs, the LCSMS might wish swap equipment between the four rigs. To cite one example, the LCSMS may wish to transfer two micromanipulators and one amplifier from one patch clamp rig to a different patch clamp rig in order to allow the second rig to be capable of six simultaneous patch recordings. To cite another, the LCSMS may wish to move a treadmill from the in vivo multiphoton rig (Rig 4) to the in vitro multiphoton rig (Rig 3) to convert the latter to in vivo use. Such flexibility requires the hardware to be compatible and (ideally) interchangeable.Anticipated period of performance: The contractor shall deliver and install the equipment within 90 days after receipt of order.Other important considerations: Quantity is four (4). Contractor shall warrant that the Equipment will be free from defects for a period of twenty-four (24) months from the date of installation, inspection by the Government and acceptance.Capability statement /information sought. Respondents must provide clear and convincing documentation of their capability of providing the products specified in this notice including providing information regarding being an authorized provider of the services.The respondent must also provide their DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc., pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements.One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2" x 11" paper size, with 1" top, bottom, left and right margins, and with single or double spacing.The information submitted must be in and outline format that addresses each of the elements of the project requirement and in the capability statement /information sought paragraphs stated herein.The response must include the respondents' technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses.All responses to this notice must be submitted electronically to the Contract Specialist. Facsimile responses are NOT accepted.The response must be submitted to Alicia Maldonado Torres, at e-mail address Alicia.maldonadotorres@nih.gov .The response must be received on or before March 25, 2019, 9:00 am, Eastern Time.Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work.Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation.Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s)."