On-chip fluorescence microscopy with a random microlens diffuser

Kuo, Grace; Liu, Fanglin Linda; Grossrubatscher, Irene; Ng, Ren; Waller, Laura

doi:10.1364/oe.382055

Cited by 56 publications

(32 citation statements)

References 30 publications

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“…Unlike scanning approaches, single-shot methods [10][11][12][13][14][15][16][17] offer faster capture speeds, with a temporal resolution limited only by the camera frame rate. These methods encode information from the entire volume into a 2D measurement and then computationally reconstruct the 3D information.…”

Section: Introductionmentioning

confidence: 99%

Miniscope3D: optimized single-shot miniature 3D fluorescence microscopy

et al. 2020

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Miniature fluorescence microscopes are a standard tool in systems biology. However, widefield miniature microscopes capture only 2D information, and modifications that enable 3D capabilities increase the size and weight and have poor resolution outside a narrow depth range. Here, we achieve the 3D capability by replacing the tube lens of a conventional 2D Miniscope with an optimized multifocal phase mask at the objective’s aperture stop. Placing the phase mask at the aperture stop significantly reduces the size of the device, and varying the focal lengths enables a uniform resolution across a wide depth range. The phase mask encodes the 3D fluorescence intensity into a single 2D measurement, and the 3D volume is recovered by solving a sparsity-constrained inverse problem. We provide methods for designing and fabricating the phase mask and an efficient forward model that accounts for the field-varying aberrations in miniature objectives. We demonstrate a prototype that is 17 mm tall and weighs 2.5 grams, achieving 2.76 μm lateral, and 15 μm axial resolution across most of the 900 × 700 × 390 μm3 volume at 40 volumes per second. The performance is validated experimentally on resolution targets, dynamic biological samples, and mouse brain tissue. Compared with existing miniature single-shot volume-capture implementations, our system is smaller and lighter and achieves a more than 2× better lateral and axial resolution throughout a 10× larger usable depth range. Our microscope design provides single-shot 3D imaging for applications where a compact platform matters, such as volumetric neural imaging in freely moving animals and 3D motion studies of dynamic samples in incubators and lab-on-a-chip devices.

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Section: Introductionmentioning

confidence: 99%

Miniscope3D: optimized single-shot miniature 3D fluorescence microscopy

et al. 2020

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“…We further compare the 3 × 3 array PSF with other configurations, including a single focus, a 2 × 3 array, and a 2 × 2 array, and show that the decorrelation generally improves with the number of foci. To further quantitatively compare the axial resolving powers of different configurations, we adopt the full width at PCC = 0.8 proposed in ( 26 ) as a heuristic estimate of the axial resolution, which gives 155 μm for the 3 × 3 array, 179 μm for the 2 × 3 array, and 206 μm for the 2 × 2 array. In the next section, we show that these PCC-based axial resolution predictions agree well with our experimental data.…”

Section: Resultsmentioning

confidence: 99%

“…Second, the lateral resolution is fundamentally limited by the NA of a single microlens. Customized aperiodic MLAs ( 19 , 26 ) having nonidentical NAs can open up a broader design space for improving the lateral resolution without compromising other imaging attributes. The axial resolution is physically limited by the total angular extent of the MLA, which can be moderately increased given the size constraint for the wearable application.…”

Section: Discussionmentioning

confidence: 99%

“…Third, the FOV is currently limited by the computational model that neglects the lateral shift variance in the image formation. This limitation can be overcome by developing reconstruction algorithms that can effectively incorporate shift-variant PSFs, such as the local convolution model ( 26 ) and deep learning algorithms ( 42 ). As observed in our experiment, the FOV is ultimately limited by the limited angular pixel response (see section S4 and fig.…”

Section: Discussionmentioning

confidence: 99%

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Single-shot 3D wide-field fluorescence imaging with a Computational Miniature Mesoscope

et al. 2020

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Fluorescence microscopes are indispensable to biology and neuroscience. The need for recording in freely behaving animals has further driven the development in miniaturized microscopes (miniscopes). However, conventional microscopes/miniscopes are inherently constrained by their limited space-bandwidth product, shallow depth of field (DOF), and inability to resolve three-dimensional (3D) distributed emitters. Here, we present a Computational Miniature Mesoscope (CM2) that overcomes these bottlenecks and enables single-shot 3D imaging across an 8 mm by 7 mm field of view and 2.5-mm DOF, achieving 7-μm lateral resolution and better than 200-μm axial resolution. The CM2 features a compact lightweight design that integrates a microlens array for imaging and a light-emitting diode array for excitation. Its expanded imaging capability is enabled by computational imaging that augments the optics by algorithms. We experimentally validate the mesoscopic imaging capability on 3D fluorescent samples. We further quantify the effects of scattering and background fluorescence on phantom experiments.

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“…This breaks the need to trade-off spatial and angular resolution, giving the best of both worlds if the sample is sufficiently sparse. Since we no longer need limiting apertures, we can even remove the objective lens, creating a lensless 3D imager that is just a sensor and a diffuser [59,[67][68][69] (Fig. 7).…”

Section: Diffusercam: a New Methods For Single-shot 3d Microscopymentioning

confidence: 99%

Roadmap on 3D integral imaging: sensing, processing, and display

et al. 2020

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This Roadmap article on three-dimensional integral imaging provides an overview of some of the research activities in the field of integral imaging. The article discusses various aspects of the field including sensing of 3D scenes, processing of captured information, and 3D display and visualization of information. The paper consists of a series of 15 sections from the experts presenting various aspects of the field on sensing, processing, displays, augmented reality, microscopy, object recognition, and other applications. Each section represents the vision of its author to describe the progress, potential, vision, and challenging issues in this field.

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On-chip fluorescence microscopy with a random microlens diffuser

Cited by 56 publications

References 30 publications

Miniscope3D: optimized single-shot miniature 3D fluorescence microscopy

Miniscope3D: optimized single-shot miniature 3D fluorescence microscopy

Single-shot 3D wide-field fluorescence imaging with a Computational Miniature Mesoscope

Roadmap on 3D integral imaging: sensing, processing, and display

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