Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications

Abstract

Despite the rapid progress in optical imaging, most of the advanced microscopy modalities still require complex and costly set-ups that unfortunately limit their use beyond well equipped laboratories. In the meantime, microscopy in resource-limited settings has requirements significantly different from those encountered in advanced laboratories, and such imaging devices should be costeffective, compact, light-weight and appropriately accurate and simple to be usable by minimally trained personnel. Furthermore, these portable microscopes should ideally be digitally integrated as part of a telemedicine network that connects various mobile health-care providers to a central laboratory or hospital. Toward this end, here we demonstrate a lensless on-chip microscope weighing 46 grams with dimensions smaller than 4.2cm × 4.2cm × 5.8cm that achieves sub-cellular resolution over a large field of view of ~24 mm 2 . This compact and light-weight microscope is based on digital in-line holography and does not need any lenses, bulky optical/mechanical components or coherent sources such as lasers. Instead, it utilizes a simple light-emitting-diode (LED) and a compact optoelectronic sensor-array to record lensless holograms of the objects, which then permits rapid digital reconstruction of regular transmission or differential interference contrast (DIC) images of the objects. Because this lensless incoherent holographic microscope has orders-of-magnitude improved light collection efficiency and is very robust to mechanical misalignments it may offer a cost-effective tool especially for telemedicine applications involving various global health problems in resource limited settings.

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.…”

Optofluidic Tomography on a Chip

“…It should be noted that despite the use of tilted illumination angles, the recorded holograms are still in-line holograms since the reference wave and the object wave propagate coaxially. As a result, an iterative phase recovery algorithm 8 based on object-support constraint is utilized to reconstruct the complex field transmitted through the object. Throughout these iterations, the optical field is propagated back and forth between the parallel hologram and object planes.…”

“…The exact value of this tilt angle is not critical and need not be known a priori; it simply ensures that the flow of the object along the microchannel generates a shift component in both x and y, enabling digital synthesis of higher resolution holograms through pixel super-resolution ͑SR͒. Owing to its unique hologram recording geometry with unit fringe magnification, 8,9 our holographic optofluidic microscopy platform permits imaging of the flowing objects using multiple illumination angles as shown in Fig. 1, which is the key to achieve optical computed tomography.…”

“…7 In the meantime, there has been a significant interest in lensfree imaging modalities toward the development of microscopes that can be integrated on a chip. 8,9 These lensfree imaging modalities can potentially allow replacing conventional bulky light microscopes with their compact and onchip counterparts for use in microfluidic systems. For the same purpose, conventional optofluidic microscopy 10 utilizes microfluidic channels to deliver the sample onto the imaging system, enabling integration of lensfree imaging with microfluidics.…”

“…In this optofluidic lensfree imaging modality, using a spatially incoherent light source ͑600 nm center wavelength with ϳ10 nm spectral bandwidth, filtered by an aperture of diameter ϳ0.05-0.1 mm͒ placed ϳ50 mm away from the sensor, digital in-line holograms 8 of the sample are recorded by an optoelectronic sensor array. ͑Aptina MT9P031STC, Aptina, San Jose, 5 megapixels, 2.2 m pixel size͒.…”