Microphotonic needle for minimally invasive endoscopic imaging with sub-cellular resolution

Abstract

Ultra-compact micro-optical elements for endoscopic instruments and miniaturized microscopes allow for non-invasive and non-destructive examination of microstructures and tissues. With sub-cellular level resolution such instruments could provide immediate diagnosis that is virtually consistent with a histologic diagnosis enabling for example to differentiate the boundaries between malignant and benign tissue. Such instruments are now being developed at a rapid rate; however, current manufacturing technologies limit the instruments to very large sizes, well beyond the sub-mm sizes required in order to ensure minimal tissue damage. We show here a platform based on planar microfabrication and soft lithography that overcomes the limitation of current optical elements enabling single cell resolution. We show the ability to resolve lithographic features that are as small as 2 μm using probes with a cross section that is only 100 microns in size. We also show the ability to image individual activated neural cells in brain slices via our fabricated probe.

Neurophotonics: a comprehensive review, current challenges and future trends

“…The spatial resolution obtained show to be suitable for in-vivo fluorescence image studies, using the compact and minimalized device. Another example of a miniaturized, minimally invasive platform is provided in Tadayon et al (2018) where authors describe a 100 μm cross-section probe for single cell resolution imaging (Figure 5F). The novelty of this work lies in the use of microfabrication methods (soft lithography, planar microfabrication) to fabricate 3D photonic elements (polymeric waveguide and polymeric micro-lens) with reduced cross-section while achieving high resolution.…”

“…Licensed under CC BY 4.0. (F) Microfabricated probe for sub-cellular level resolution endoscopic imaging(Tadayon et al, 2018). Licensed under CC BY 4.0.…”

Two‐Photon Polymerization Lithography for Optics and Photonics: Fundamentals, Materials, Technologies, and Applications

“…To demonstrate the advantages of integration and one-shot fabrication, endoscope and fiber imaging system are manufactured with the microlens system to achieve high quality imaging, the unique functionalities exceed the performance of original systems. [134,500,510,512] For example, Gissibl et al built the aspherical multi-lens system to help correct the aberration and to provide a wide angle of view as shown in Figure 10a. [134] In Figure 10b, similarly, Li et al explored how to reliably create the side-facing imaging optics as a function of optical coherence tomography (OCT) probe.…”

Single-cell micro- and nano-photonic technologies

“…This ground-breaking approach has recently enabled 3D, sub-cellular resolution imaging of dendrites and dendritic spines in the mice dorsal striatum as well as spatially resolved Ca 2+ imaging in rat organotypic hippocampal slices with a 50 µm-core optical fiber [102]. On the other hand, innovative micro-fabrication approaches have been recently employed to achieve cellular resolution imaging using a mm-long probe with a high numerical aperture lens monolithically integrated on a polymeric waveguide [103].…”