Field-portable wide-field microscopy of dense samples using multi-height pixel super-resolution based lensfree imaging

Abstract

We report a field-portable lensfree microscope that can image dense and connected specimens with sub-micron resolution over a large field-of-view of ~30 mm(2) (i.e., ~6.4 mm × ~4.6 mm) using pixel super-resolution and iterative phase recovery techniques. Weighing ~122 grams with dimensions of 4 cm × 4 cm × 15 cm, this microscope records lensfree in-line holograms of specimens onto an opto-electronic sensor-array using partially coherent illumination. To reconstruct the phase and amplitude images of dense samples (with >0.3 billion pixels in each image, i.e., >0.6 billion pixels total), we employ a multi-height imaging approach, where by using a mechanical interface the sensor-to-sample distance is dynamically changed by random discrete steps of e.g., ~10 to 80 μm. By digitally propagating back and forth between these multi-height super-resolved holograms (corresponding to typically 2-5 planes), phase and amplitude images of dense samples can be recovered without the need for any spatial masks or filtering. We demonstrate the performance of this field-portable multi-height lensfree microscope by imaging Papanicolaou smears (also known as Pap tests). Our results reveal the promising potential of this multi-height lensfree computational microscopy platform for e.g., pathology needs 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.…”

Quantitative phase imaging by wide field lensless digital holographic microscope

“…The pixel size limited resolution restricts the applications for only telemedicine and for resource limited setting. The so called pixel-super resolution approaches are possible solutions to increase the resolution [16][17][18]. The development in the manufacturing of sensors with smaller pixel size will further extend it applications fields.…”

“…This requires a microscope objective and mechanical alignment components. The group of Aydogan Ozcan proposed a new lensless digital holographic microscope which is capable of imaging samples with a field of view corresponding to the entire sensor active area with a resolution in the order of the pixel size of the sensor [1], [14][15][16][17][18].The main key concepts of this setup in contrast to the well-known lensless systems are the use of an LED with a pinhole of size ~ 50-100 µm as point source to achieve a high throughput and the placing of the sensor chip closer to the sample.…”

Giga-pixel imaging on a chip: High numerical aperture lensfree microscopy over a wide field-of-view

“…This partially coherent beam is generated by a fiber-coupled light source (Xenon-lamp connected to a monochromator with a spectral bandwidth of 3 nm centered at 530 nm). The wavelength of the light source can be tuned within the visible range, and for field portable implementations we can also utilize various light emitting diodes (LEDs) as we already demonstrated in our earlier work [7], [8], [14], [16].…”