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Lensfree Holographic Microscopy and Wide-field Optical Imaging using Wetting Films and Nano-Lenses

Abstract

Impressive revolution of optical imaging and microscopy architectures has been expanding our horizon and increasing the opportunities in medical diagnostics. Although we experience significant advancements such as better resolution, speed and throughput, advanced imaging platforms are still complex, bulky and expensive, such that their function beyond well-established clinical environment is quite limited. Therefore, innovative imaging techniques are necessary to combat global health problems in resource-scarce settings where health care infrastructure is extremely limited or does not even exist. In such poor settings, imaging devices should be compact, robust, cost-effective and easy to use, without a trade-off in their performance.

Centered on this vision, here I demonstrate a new lensfree on-chip microscopy and nano-particle imaging platform based on partially-coherent digital in-line holography, providing a highly-sensitive and high-throughput approach for rapid medical diagnostics and screening, especially for field settings and resource-limited environments. This computational microscopy and nano-particle imaging platform achieves subcellular spatial resolution and also directly images, for the first time in on-chip microscopy, single sub-100 nm particles using self-assembled aspheric liquid nano-lenses around individual nano-particles across a large field-of-view of >20 mm2, i.e., more than two orders-of-magnitude larger than existing nano-imaging techniques.

This platform does not utilize any lenses, lasers or other bulky optical/mechanical components which greatly simplifies its architecture making it portable, light-weight, and cost-effective. It has been successfully implemented on a compact stand-alone unit which weighs only ~46 grams with dimensions smaller than 4.2 x 4.2 x 5.8 cm as well as on a commercially-available cell-phone that is modified with a light-weight (~ 38 grams) hardware attachment.

Using stable and biocompatible wetting films to self-assemble aspheric liquid nano-lenses around individual nano-particles, I also introduce a wide-field on-chip microscopy modality that is capable of directly imaging single nano-particles and viruses (i.e., adenoviruses and influenza A (H1N1) viral particles) within a field-portable design.

Creating new opportunities for rapid medical diagnostics in point-of-care and field conditions, this lensfree microscopy and nano-particle imaging toolset may bring improved healthcare delivery especially to resource-poor regions of the world and may significantly benefit our fight against various global health challenges including HIV, malaria, waterborne diseases and viral infections.

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