A Miniature Microscope for Multi-contrast Optical Imaging in Animals

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Unmet Need
The past two decades have witnessed a surge of new imaging contrast agents and mechanisms, as well as seen the introduction of novel imaging techniques. One such exciting development is ‘multicontrast imaging’, where several distinct imaging techniques are combined to simultaneously interrogate multiple physiological variables. This kind of approach permits a more holistic characterization of the preclinical disease microenvironment or organ system being studied, thereby providing greater insight into disease etiology and response to therapy.
Specifically, neuroimaging, i.e. imaging the brain at rest or during activity, stands to significantly benefit from multicontrast imaging approaches. Brain function and dysfunction are governed by a complex multi-variable building block called the ‘neurovascular unit’. Studying the healthy neurovascular unit and how it becomes dysfunctional in different diseases ranging from brain cancer to Alzheimer’s disease requires imaging techniques capable of interrogating neuronal activity, blood flow and oxygenation. The same is true for many other organ systems such as the kidney, liver, lungs etc.
However, today’s multicontrast imaging instruments tend to be large, benchtop-based systems. This is because building such an instrument requires incorporating components needed for not just one, but multiple imaging techniques. Moreover, such systems require many costly components, need to be custom-built, and honed by those possessing expert technical knowledge. These limitations have restricted the widespread use of multicontrast imaging and have precluded its use for interrogating brain function in awake and freely behaving animal experiments. Therefore, there exists a crucial need for multicontrast imaging systems that are ultra-miniaturized (i.e. weigh only a few grams), portable, low-cost and capable of being conveniently operated in the preclinical setting by non-expert users.

Technological Overview:
The inventors have developed a miniature microscope for multicontrast optical imaging that is a portable, ‘plug and play’ device, and requires minimal technical expertise to operate. Furthermore, it costs a fraction of what a benchtop multi-contrast imaging system costs, and has a miniature footprint that is ideal for preclinical studies. This technology is based on recent advances in miniaturized opto-electronics and 3D printing techniques. The microscope is 5 cm3 and weighs less than 9 grams. The weight is further reduced to 3 grams via a flexible strain relief system. This microscope captures images of neural activity by incorporating a fluorescence channel in addition to three different channels for hemodynamic imaging.  The inventors have demonstrated five major applications of this ultraportable device. The first is utilizing the technology to distinguish between neuronal activation and concomitant changes in blood flow and blood volume. The second is to differentiate between blood vessel compliance and blood flow dynamics during arousal from anesthesia. The third is using a synchronization channel built into the microscope to conduct simultaneous neuroimaging and EEG recording. The fourth is enabling multi-contrast functional brain imaging and wide-area mapping analogous to functional MRI studies. The fifth is interrogating brain cancer-induced alterations in the cerebrovasculature over the lifetime of the pathology. Additional applications envisioned include the study of stroke, immune modulation in the brain, high-throughput drug testing, infectious disease research, BSL4-type rodent studies, neurodegenerative disorders, CRISPR edited transgenic mouse phenotyping, and correlations of functional imaging with behavioral assays.

Stage of Development:
The inventors have designed, fabricated, validated and demonstrated the utility of this miniature microscope in several preclinical biomedical applications. They are seeking a partner for scaling up production, sales and commercialization.

Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
A MINIATURE MICROSCOPE FOR MULTI-CONTRAST OPTICAL IMAGING IN ANIMALS PCT: Patent Cooperation Treaty United States 16/628,859 11,867,892 1/6/2020 1/9/2024 6/25/2040 Granted
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