A groundbreaking advancement in optical technology promises to transform how we visualize the inside of the human body. Researchers have successfully developed an ultra-thin optical imager, offering a less invasive approach to acquiring high-resolution images from within internal organs and tissues. This innovation holds immense potential for early and precise disease detection, providing crucial insights that can guide more timely and effective medical treatments.
Traditional endoscopes, commonly used for internal imaging, are often bulky devices comprising cameras and thick fiber optic bundles, making them challenging to maneuver in delicate or deep anatomical regions and potentially causing tissue damage. In stark contrast, this new ultra-thin optical imager is remarkably compact, measuring a mere 7 microns thick – about one-tenth the diameter of a human eyelash – and approximately 10 millimeters long. This unprecedented miniaturization makes it ideal for navigating intricate internal body pathways with minimal invasiveness.
The researchers demonstrated the ultra-thin optical imager’s capabilities in a mouse brain, successfully performing both structural and functional imaging of neural activity. The flexible design also allows for customization of the imager’s width, enabling adaptation to various anatomical targets and desired imaging resolutions. The potential applications are vast: the microimager could be implanted for short- or long-term monitoring, attached to catheters to visualize the gastrointestinal tract or the inside of blood vessels, or even integrated with surgical tools to provide real-time visual feedback, thereby improving surgical outcomes and reducing complications.
The core of this ultra-thin optical imager is a flexible photonic platform built using Parylene, a biocompatible and transparent polymer. The research team initially developed Parylene photonics for creating tiny implantable devices that deliver targeted light within tissues. In this new work, they leveraged the bidirectional capability of Parylene waveguides – their ability to both deliver and detect light – to construct an array specifically designed for imaging tissue structure and function. The microimager features waveguides, each equipped with a micromirror at both ends. Some waveguides illuminate the tissue, while others collect the backscattered light via their micromirrors. This collected light is then channeled through individual waveguides to the back end of the device, where it is projected onto an image sensor array. Essentially, each waveguide functions as a relay for a single pixel of the tissue image.
The fabrication process for these tiny ultra-thin optical imager endoscopes utilizes microscale techniques akin to those employed in microelectronics and microelectromechanical systems (MEMS). This approach allows for easy customization of the waveguides and micromirrors, enabling tailored imaging for different tissues and desired resolutions.
Beyond the initial demonstrations with fluorescent microspheres, the researchers successfully captured fluorescent images of mouse brain tissue expressing green fluorescent protein. More importantly, they demonstrated functional neural imaging from mouse brain tissue expressing genetically encoded calcium indicators, confirming the microimager’s ability to capture actual neural function. These functional optical images were validated by comparing them with ground truth electrophysiology recordings, showing a strong correspondence between the optical data and electrical activity.
This pioneering work is a crucial step towards the broader goal of imaging neural tissue in action and eventually correlating neural activity with the genetic profiles of specific cell types. The next phase of development involves integrating light sources, image sensor arrays, and filters into the ultra-thin optical imager device’s back end to create a fully integrated, standalone microimager for in vivo applications. Such a device could revolutionize the monitoring of remnant cancer cells post-surgery or the progression of diseases after treatment, marking a significant leap forward in precision medicine.
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