We report a novel microfluidics-based lensless imaging technique, termed optofluidic microscopy (OFM), and demonstrate Caenorhabditis elegans imaging with an OFM prototype that gives comparable resolution to a conventional microscope and a measured resolution limit of 490 ¡ 40 nm.Optical imaging of samples in a biological or clinical setting is generally performed with expensive and bulky microscope systems. The imaging process can be time consuming and labor intensive. A cheaper and automated microscope that is implementable on a microfluidic platform can dramatically simplify and improve imaging procedures and related applications in biomedicine.The major advantages of microfluidic devices include their compactness and low cost. While excellent solutions to a range of important miniaturization challenges, such as fluidic transportation, 1 sample manipulation, 2 chemical sensing 3 and sample sorting, 4 have all been demonstrated, sub-micron on-chip optical imaging remains an unresolved issue. The high resolution imaging requirement in existing microfluidic systems is still fulfilled by using bulky conventional microscopes, 5,6 which obviates the cost and size advantages of micro analysis systems. (As a point of reference, a commercial conventional microscope has resolution that ranges from y1 mm to 0.2 mm depending on the objective's numerical aperture and the wavelength used.) One possible low-resolution imaging strategy is to stack the sample directly on top of a two-dimensional sensor array and illuminate the sample with a uniform light field. However, the resolution of the resulting transmission image is governed by the sensor's pitch size, which is typically 5 mm or larger-achieving microscope level resolution is difficult with this method. Using this approach, Lange et al.7 demonstrated a compact, on-chip imaging device with fair resolution (.10 mm).In this Communication, we report on an on-chip high resolution and high throughput imaging technique, termed optofluidic microscopy (OFM). The OFM's resolution is not limited by the actual pixel size of the detection sensors. Our prototype is able to image micro-organisms with resolution that is comparable to a conventional microscope. Further, the OFM does not require the use of any bulk optical elements and can potentially be used to create compact systems that are only limited in size by the underlying linear array sensor.The OFM device consists of an opaque metal film with an etched array of submicron apertures and a PDMS microfluidic chip that is bonded onto the metal film. In our experiments, the fabrication of the aperture array and the microfluidic chip was carried out in two separate steps. To fabricate the aperture array, 90 nm thick aluminium was first evaporated onto a quartz wafer. Then the pattern of the aperture array (diameter D = 600 nm; spacing = 5 mm) was defined on a PMMA resist by e-beam lithography (JEOL 9300), and subsequently transferred into the aluminium layer by reactive ion etching. The microfluidic structure was fabricated on a Mic...
Tomographic phase microscopy (TPM) is an emerging optical microscopic technique for bioimaging. TPM uses digital holographic measurements of complex scattered fields to reconstruct three-dimensional refractive index (RI) maps of cells with diffraction-limited resolution by solving inverse scattering problems. In this paper, we review the developments of TPM from the fundamental physics to its applications in bioimaging. We first provide a comprehensive description of the tomographic reconstruction physical models used in TPM. The RI map reconstruction algorithms and various regularization methods are discussed. Selected TPM applications for cellular imaging, particularly in hematology, are reviewed. Finally, we examine the limitations of current TPM systems, propose future solutions, and envision promising directions in biomedical research.
This paper reviews the current state of research in spectral domain optical coherence tomography (SDOCT). SDOCT is an interferometric technique that provides depth-resolved tissue structure information encoded in the magnitude and delay of the back-scattered light by spectral analysis of the interference fringe pattern. There are two approaches to SDOCT--one that uses a broadband source and a spectrometer to measure the interference pattern as a function of wavelength and the other that utilizes a narrowband tunable laser that is swept linearly in k approximately 1/lambda space during spectral fringe data acquisition. Unlike time domain (TD) OCT, the reference arm is stationary in both SDOCT methods, which allows for ultra high-speed OCT imaging. Owing to its high speed and superior sensitivity, SDOCT has become indispensable in biomedical imaging applications. After a brief introduction and a discussion on sensitivity advantage, methods of implementation of the two SDOCT schemes will be presented. The two peer approaches are compared in speed, scan depth range, complexity, spectral regions of operation, and methods of detection. The review also discusses OCT enhancements and functional methods based on SDOCT format and concludes with possible directions that this research may take in the near future.
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