Miniaturized integration of a fluorescence microscope

Abstract

The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals towards relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including semiconductor light source and sensor. This device enables high-speed cellular-level imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens.

Prolonging the postcomplex spike pause speeds eyeblink conditioning

“…It is known from in vivo imaging and multielectrode array measurements that temporally correlated complex spikes occur in parasagittally oriented modules of PNs within the cerebellar cortex (40)(41)(42)(43), and recent evidence is consistent with the idea that the CF-associated teaching signal is encoded by temporally correlated complex spike activity (44). The axons of PNs are inhibitory and converge on single DCN neurons, thus prolonged post-CxSp pauses occurring synchronously in a module of PNs could provide an extended window of disinhibition to the DCN cells receiving such input (45,46).…”

Handheld high-throughput plasmonic biosensor using computational on-chip imaging

“…Similarly, various point-of-care diagnostic devices have been developed and among them optical imaging and sensing techniques are highly advantageous as they can provide real-time, highresolution and highly sensitive quantitative information, potentially assisting rapid and accurate diagnosis. [30][31][32][33][34][35][36][37][38][39][40] To date, a number of optical techniques have been proposed for point-of-care diagnostics such as in vitro optical devices, [41][42][43][44][45][46][47][48][49][50][51][52][53] including portable optical imaging systems, optical microscopes integrated to cell phones or in vivo optical devices, [54][55][56][57][58][59][60][61][62][63] involving confocal microscopy, microendoscopy and optical coherence tomography techniques. Among these approaches, lens-free computational on-chip imaging 64 has been an emerging technique that can eliminate the need for bulky and costly optical components while also preserving (or even enhancing in certain cases) the image resolution, field of view and sensitivity.…”

On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids

“…In contrast, the microfluidic chip presented here is much simpler in design, can be mass-fabricated at a low cost, and allows at the same time MV identification, as well as size and concentration measurements. Thus, it opens the possibility to be used as a diagnostic tool that combine low cost, ease of use, and sensitivity 29,30 . A meaningful concentration and size distribution could only be obtained when using sheet illumination.…”