IntraVital Microscopy is an all-in-one confocal/two-photon microscopy system designed and optimized for longitudinal imaging of live animal models in vivo. This is the first all-in-one intravital microscopy platform that can explore complex dynamic behaviors of numerous cells in a living body and serve as a next-generation core technology to elucidate unknown pathophysiology of various human diseases. Confocal capabilities of the IVM system enables optical sectioning of in vivo tissue via rejection of out-of-focus fluorescence light coming from the background tissue which will result in images with high contrast and quality. In addition to confocal, IVM systems are equipped with two-photon lasers which use longer-wavelength near-infrared (NIR) fs-pulse excitation capable of deep tissue imaging as well as label-free, non-linear multi-harmonic generation imaging (SHG, THG).
With this technique, it is possible to distinguish an individual cell among a large number of cells in various organs, which is not possible with conventional biomedical imaging technologies such as MRI or CT, and to track the movement of each cell in three dimensions in real-time. It is the world’s first system to fully integrate body temperature regulation and anesthesia into the animal handling stage. The system also includes state-of-the-art live tissue motion compensation for improved image quality, along with ultrafast imaging speeds. The system may be configured for confocal or two/multi-photon microscopy, using either solid-state or femto-second pulsed lasers, respectively.
IVIM Technology was founded on the innovative technology of IntraVital Microscopy (IVM) developed by the Korea Advanced Institute of Technology (KAIST). First founded in 2017, IVIM Technology released the IVM-C and IVM-CM models in 2018. The IVM-M and IVM-MS models were released later in 2019. In mid-2020, a US-based reference site was established at Harvard Medical School in Boston, MA.
Intravital microscopy enables dynamic, 3D, cellular-level imaging of various biological processes in vivo. It enables scientists to directly verify hypothesis derived from ex vivo or in vitro observations in natural physiological in vivo microenvironments.
Using intravital microscopy, in vivo visualizations of gene expression, protein activity, cell trafficking, cell-cell / cell-microenvironment interactions, and various physiological responses to stimuli have been accomplished, providing novel insights, which have been impossible to obtain with conventional static 2D observation of ex vivo or in vitro samples.
However, up until now, individual users have had to improvise the required functions for each of the intravital imaging applications for the various organs with conventional standalone microscopes, which resulted in non-optimal performance for limited applicability.
The IntraVital Microscopy (IVM) systems from IVIM Technology, is a fully integrated system with optimized optical, mechanical, and electrical components to ensure best-in-class imaging performance for a wide range of in vivo intravital imaging applications.
The IVM systems (IVM-C/M/CM/MS) provide an all-in-one in vivo imaging solution providing integrated physiological monitoring and support, anesthesia, along with state-of-the-art living tissue motion compensation for improved image quality. The software has been fully optimized to allow for rapid image acquisition, while image processing is accelerated by GPU-assisted parallel computing.
| Feature | Benefit |
| Integrated temperature support, and physiological monitoring | Ensures animal well-being throughout the imaging session, and consistency between animals within a study
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| Integrated inhaled anesthesia | Ensures ease of animal handling and consistent plane of anesthesia |
| Animal motion compensation | Provides enhanced image quality on organs which may be affected by respiratory motion
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| User friendly design – both software and hardware | Allows for ease of use, and reproducible results |
| 4-color simultaneous imaging | Confocal / Two-Photon Modes – Allows users to track the movement of several cells in vivo to better understand the biological processes being examined |
| Ultrafast rotating polygonal mirror scanner |
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| IVIM-C3 | IVM-M3 | IVM-CM3 | IVM-MS3 | IVM-CMS3 | |
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| Laser | |||||
| Type | Confocal Laser Unit | Tunable Two-Photon Laser Unit Ti:Sapphire laser |
Confocal Laser Unit Tunable Two-Photon Laser Unit Ti:Sapphire laser |
Compact Two-Photon Laser Unit | Confocal Laser Unit Compact Two-Photon Laser Unit |
| Wavelength | 405 nm (20mW), 488 nm (20mW), 561 nm (20mW), 640 nm (20mW) |
690 – 1,050 nm | For Confocal 405 nm (20mW), 488 nm (20mW), 561 nm (20mW), 640 nm (20mW) For Two-Photon 690-1,050 nm |
Fixed 920 nm | For Confocal 405 nm (20mW), 488 nm (20mW), 561 nm (20mW), 640 nm (20mW) For Two-Photon Fixed 920 nm |
| Fluorescence | |||||
| Detector | Confocal Detector Wavelength: 185 – 900 nm (DAPI, CFP, GFP, YFP, RFP, Cy5, Cy5.5, etc.) 4 Ultra-broadband high SNR PMTs (UV to Near IR, Ultra High Sensitivity, Low Dark Current) 25-2,000 μm variable pinhole |
Two-Photon Detector Wavelength: 185 – 760 nm (DAPI, CFP, GFP, YFP, RFP, Cy5, Cy5.5, etc.) 4 High quantum efficiency PMTs (UV to Near IR, Ultra High Sensitivity, Low Dark Current) |
Confocal Detector Wavelength: 185 – 900 nm (DAPI, CFP, GFP, YFP, RFP, Cy5, Cy5.5, etc.) 4 Ultra-broadband high SNR PMTs (UV to Near IR, Ultra High Sensitivity, Low Dark Current) 25-2,000 μm variable pinhole Two-Photon Detector Wavelength: 185 – 760 nm (DAPI, CFP, GFP, YFP, RFP, Cy5, Cy5.5, etc.) 4 High quantum efficiency PMTs (UV to Near IR, Ultra High Sensitivity, Low Dark Current) |
Two-Photon Detector Wavelength: 185 – 760 nm (DAPI, CFP, GFP, YFP, RFP, Cy5, Cy5.5, etc.) 4 High quantum efficiency PMTs (UV to Near IR, Ultra High Sensitivity, Low Dark Current) |
Confocal Detector Wavelength: 185 – 900 nm (DAPI, CFP, GFP, YFP, RFP, Cy5, Cy5.5, etc.) 4 Ultra-broadband high SNR PMTs (UV to Near IR, Ultra High Sensitivity, Low Dark Current) 25-2,000 μm variable pinhole Two-Photon Detector Wavelength: 185 – 760 nm (DAPI, CFP, GFP, YFP, RFP, Cy5, Cy5.5, etc.) 4 High quantum efficiency PMTs (UV to Near IR, Ultra High Sensitivity, Low Dark Current) |
| Variable Emission Filter (Optional) |
6 or 2 emission filters can be mounted on each of four detectors |
| ScanHead | |
| Scanner | Polygonal mirror (Fast axis scanning, Max. 66 kHz) Galvano scanner (Slow axis scanning, Max. 200 ㎲ /step) |
| Imaging Head | |
| Objectives | Max. 5 objectives are mountable on S/W controlled motorized turret (1X – 100X) Compatible for commercial objectives |
| Image | |
| FOV | 100 x 100 ㎛ ² – 10 x 10 mm² |
| Pixel Resolution | Max. 2,048 x 2,048 pixels |
| Imaging Speed | Standard : 30 fps @ 512 x 512 pixels (Optional) High Speed : 60 fps @ 512 x 512 pixels (Optional) Ultra High Speed : 100 fps @ 512 x 512 pixels |
| In vivo Animal Stage | |
| 3D Stage | Travel Range : 50,000 x 50,000 x 75,000 ㎛ (XYZ) Micromanipulation (Max. 0.2 ㎛ resolution) 3-axis independent control with Jog Dial & S/W |
| Animal Motion Compensation | |
| 4D In Vivo Imaging Motion Compensation |
XY motion compensation: Averaged image acquisition with motion artifact compensation Z motion compensation: Image-based sample Z position adjustment for long-term intravital microscopic imaging & sample tracking (Feedback-loop automatic stage control) T motion compensation : Image-based image XY position adjustment for long-term intravital microscopic imaging & sample tracking (Feedback-loop automatic stage control) Combination of above three compensation for 4D in vivo motion compensation Controllable by IVM Engine software |
| Additional In Vivo Modules | |
| Live Animal Maintenance Unit |
Body Temp. Monitoring & Feedback Heater Control including tablet PC 4CH Rectal Probe, Body Plate Heater, Thermometer Sensor & Cover Glass Heater |
| In Vivo Imaging Chamber SET |
Standard Dorsal Skinfold Chamber SET Lung Imaging Chamber SET Cranial Window SET Abdominal Imaging Window SET Pancreas Imaging Window SET Mammary Imaging Window SET Heart Imaging Window SET |
| Inhalation Anesthesia System |
Rodent Animal Inhalation Anesthesia System Anesthesia Mask and Connections |
| Engine & Studio Software | |
| Image Display | Independent 4 single channel display (RGBA channel) Overlay channel display (Selection among RGBA channel) |
| In Vivo Imaging Mode | Mosaic imaging (XY), Z-stack imaging (Z), Time-lapse imaging (T) Time-lapse imaging at Multi-position (T- M), Time-lapse & Z-stack imaging (TZ), Time-lapse & Z-stack imaging at Multi-position (TZ- M) |
Confocal Microscopy
- High-resolution optical sectioning imaging of in vivo tissue
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- Rejection of fluorescence signal from out-of-focus volume by confocal pinhole
- High contrast, low background, high quality in vivo imaging
- Ultrafast precise Raster scanning of multi-color excitation laser-beam focus
- Video-rate imaging of fast cellular-level dynamics in live tissue in situ
- Ideal for high-sensitivity multi-color intravital imaging of in vivo tissue
Two-Photon Microscopy
- High-resolution optical sectioning imaging of in vivo tissue
- Fluorescence signal is intrinsically generated only at the focus
- Deeper tissue imaging with longer-wavelength near-infrared (NIR) fs-pulse laser for two-photon / multi-photon excitation
- Capable of label-free, non-linear multi-harmonic generation imaging (SHG, THG)
- No photo-bleaching at non-focal plane; reduced phototoxicity
- Ideal for long-term 3D intravital imaging of in vivo tissue
| Confocal Microscopy | Two-Photon Microscopy |
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Applications
The IVM series of systems have been designed to provide expandability and flexibility for highly diverse intravital imaging applications of various tissues and organs, including the brain, liver, spleen, kidney, pancreas, lung, heart, gastrointestinal tract, retina, skeletal muscle, bone marrow, peripheral lymph node, prostate, thymus, thyroid gland, adipose tissue, blood, and lymphatic vessels, etc.
In addition, to handle various imaging needs raised by researchers for a wide range of biomedical studies, detailed experimental protocols have been established for high-quality intravital image acquisition.
Subsequent quantitative analysis of various cellular-level dynamics and physiological alterations have been established.
- In Vivo Live Cell Imaging
- IVM systems allow for dynamic 3D imaging of various cellular-level dynamics such as cell trafficking, cell-cell interaction, cell-microenvironment interactions in vivo; providing insights into the processes of human disease progression and response to therapeutic interventions
- Drug Discovery
- The IVM series of systems serve as a highly valuable and versatile tool allowing:
- Target identification and validation in natural in vivo microenvironments
- Confirmation of mode of action (MoA) and proof of concept (PoC) of new therapeutics by direct in vivo cellular observation
- Monitoring of in vivo drug delivery, distribution, retention and in situ efficacy at target tissues and organs
- Select Imaging Examples
- Inguinal Adipose Tissue
- Inguinal Adipose Tissue
- The IVM series of systems serve as a highly valuable and versatile tool allowing:
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- Neuromuscular Junction
- Neuromuscular Junction
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- Immune Cell Imaging
- Nanoparticle Imaging in the Liver
- Retinal Imaging
- Xenograft Imaging
- Immune Cell Imaging
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Accessories and Add-ons
The various IVM models have the following optional add-on items:
- Integrated inhaled anesthesia system
- Optional high (60fps) or ultra-high (100fps) speed scanning module
- Optional objective lens set for two-photon or confocal imaging
- In vivo imaging chamber
- Lung imaging chamber
- Cranial window
- Abdominal window
- Pancreas imaging window
- Mammary imaging window