Sub-pixel resolving optofluidic microscope for on-chip cell imaging

Abstract

We report the implementation of a fully on-chip, lensless, sub-pixel resolving optofluidic microscope (SROFM). The device utilizes microfluidic flow to deliver specimens directly across a complementary metal oxide semiconductor (CMOS) sensor to generate a sequence of low-resolution (LR) projection images, where resolution is limited by the sensor's pixel size. This image sequence is then processed with a pixel super-resolution algorithm to reconstruct a single high resolution (HR) image, where features beyond the Nyquist rate of the LR images are resolved. We demonstrate the device's capabilities by imaging microspheres, protist Euglena gracilis, and Entamoeba invadens cysts with sub-cellular resolution and establish that our prototype has a resolution limit of 0.75 microns. Furthermore, we also apply the same pixel super-resolution algorithm to reconstruct HR videos in which the dynamic interaction between the fluid and the sample, including the in-plane and out-of-plane rotation of the sample within the flow, can be monitored in high resolution. We believe that the powerful combination of both the pixel super-resolution and optofluidic microscopy techniques within our SROFM is a significant step forwards toward a simple, cost-effective, high throughput and highly compact imaging solution for biomedical and bioscience needs.

Aperture-scanning Fourier ptychography for 3D refocusing and super-resolution macroscopic imaging

“…2(c) remains 11 µm (pixel size *2), limited by the problem of pixel aliasing. Pixel aliasing is a limiting factor for many imaging applications [31,32]. The experimental results shown in Fig.…”

“…Drawing connections and distinctions between camera-scanning FP and three related imaging modalities -pixel super-resolution imaging [31,32,44,45], synthetic aperture imaging [46,47], and integral imaging [48][49][50] -helps clarify the operation of our approach. Pixel super-resolution imaging stitches together many sub-pixel shifted images in the spatial domain.…”

Three-dimensional deconvolution microfluidic microscopy using a tilted channel

“…This includes conventional microscopes (e.g., objectives) with modified slide stages as well as lensless optofluidic microscopes. [1][2][3] The fluid displacement increases sample throughput, provides control over sample sorting, 4 and gives an additional degree of freedom for imaging. To date, in-plane flow has been used to generate two-dimensional (2-D) images by displacing the target over a one-dimensional (1-D) array of detectors, 1 or to slightly displace the sample and generate subpixel-resolution images 2 and holograms.…”

Boosting detection sensitivity by using a surface-wave-enabled darkfield aperture (SWEDA)

“…The use of complementary metal-oxide-semiconductor (CMOS) integrated circuit (IC) technology for biological and biomedical applications is a good example of this engineering trend. A variety of CMOS chip-based analytical instruments have been developed in the past years, such as an optofluidic microscope [1,2], a magnetic cell manipulation system [3], a microarray platform for DNA and protein analysis and diagnostics [4], a wide field of view microscope [5], and microelectrode arrays for monitoring cell activity [6]. In contrast with conventional clinical platforms, which are bulky with high power consumption, CMOS chip-based instruments meet the growing need for hand-held, miniaturized, and highly automated devices for point-of-care biological testing.…”