SUMMARY
UCLA researchers in the department of Chemistry & Biochemistry have developed a method and device that is able to take real-time optical images of fluorescent probes for both in-vitro and in-vivo work.
BACKGROUND
Optical imaging uses light and special reflective properties of photons to obtain detailed images of a wide variety of biological systems. It is widely used to study cells and smaller organisms using fluorescent microscopy. Fluorescent imaging in vivo is challenging due to substantial scattering and autofluorescence at visible (350-700 nm) wavelengths. Therefore, in vivo imaging extensively uses near-infrared (700-1000 nm) wavelengths. Being limited to the NIR region makes it difficult to conduct multiplex imaging experiments due to the narrow wavelength bandwidth. This significantly limits the ability to deploy this technology for use in laboratory and clinical settings.
To address the challenges of low spatial and temporal resolution during in vivo imaging, other optical systems need to be explored. Some of the most promising optical imaging systems use shortwave infrared light (SWIR, in the range of 1000-2000 nm) which has a high range of contrast and resolutions. These wavelengths can penetrate multiple skin layers allowing for imaging through skin while using much less energetic, and therefore safer, wavelengths such as X-rays. Utilizing SWIR for in vivo imaging enables multicolor whole-animal imaging at video rate speeds and sub-millimeter resolution.
INNOVATION
UCLA researchers have developed fluorophore probes and an excitation and detector system that is able to selectively excite the fluorophore probe at NIR or SWIR wavelengths while limiting other wavelengths from interfering. This results in the generation of high contrast images both in in vitro and in vivo with real time imaging. During testing with mice, the system was able to clearly illuminate the vasculature and liver in mice without the need for invasive surgery. This was done both while the mouse was asleep and when it was awake and in motion capturing images at a frame rate greater than 25 frames per a second with minimal resolution loss. Furthermore, this innovation was shown to be able to excite and detect multiple probes at various wavelengths with real time imaging capability. This allows for examining multiple probes simultaneously, facilitating real time imaging of a variety of targets.
POTENTIAL APPLICATIONS
- In-vivo mice studies
- Cancer screening
- Multi-wavelength microscopy studies
ADVANTAGES
- Non-invasive technology
- Real-time imaging and imaging acquisition in vivo irrespective of the location
- High photon efficacy i.e. ability to penetrate multiple skin layers
- Ease of collecting multiple images on a single detector
- Lower radiation exposure compared to similar imaging technologies such as X-ray or PET
- Can excite and/or detect multiple wavelengths
- Has a high frame rate allowing for real time imaging of samples
DEVELOPMENT-TO-DATE:
UCLA researchers have tested the devices both in vitro and in vivo and shown clear distinguishable images of fluorophores with different biodistribution and localization. They have shown the device can excite and detect multiple fluorophore probes simultaneously. The detection devices have been rigorously tested on a wide range of samples at real time at a high frame rate >25 frames per second.
Related Papers (from the inventors only)
Cosco ED, er al. (2020), Nat Chem, Nat Chem. 2020 Dec;12(12):1123-1130