3.8 Proceedings Paper

Two-dimensional microlens array for low-cost high-resolution bio-imaging

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SPIE-INT SOC OPTICAL ENGINEERING
DOI: 10.1117/12.2650896

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Microsphere assisted microscopy; Microlens array; Resolution enhancement; Dark field microscopy; Phase contrast microscopy; Fluorescence microscopy

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Mobile microscopes with a low-cost imaging substrate containing a two-dimensional microlens array enable multi-modal imaging with resolution beyond the diffraction limit. The substrate can be easily attached and detached from the sample, allowing imaging with sub-400nm resolution using a low magnification objective lens. This technique provides a low-cost and easy-to-use method for improving the resolution of multi-modal imaging systems.
Mobile microscopes, which are cost-effective and field-portable, are rapidly gaining popularity for a variety of different applications, including disease diagnostics. Different imaging modalities, based on transmission, absorption, scattering, phase change, and fluorescence have been developed, depending on the specific application. Mobile microscopes are typically designed to have single magnification, and the maximum achievable resolution is limited by the numerical aperture (N.A.) of the objective lens, due to diffraction of light. Here we present a low-cost imaging substrate containing a two-dimensional (2D) microlens array that enables multi-modal imaging ( phase-contrast, dark-field, and fluorescence) with resolution beyond the diffraction limit. The substrate is placed in contact with the sample to form a sandwich structure and the image magnification is attributed to the formation of virtual images by the individual microspheres. This reusable substrate can be easily attached to and detached from the sample, with minimal to no sample damage. A variety of different sizes of glass microspheres (40- 500..m) were explored and their performance was characterized using fluorescent particles (200 nm - 1 mu m). The substrate enabled imaging with sub-400nm resolution, using a low magnification objective lens with N.A.similar to 0.25. Proof-of-concept experiments with this substrate were performed by imaging mammalian tissues, red blood cells, including sickle cells. This technique provides a low-cost, easy- to-use method of improving the resolution of multi-modal imaging systems, which is particularly useful for mobile microscopy applications.

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