Kaiqin Chu

Cell-Phone-Based Platform for Biomedical Device Development and Education Applications

In this paper we report the development of two attachments to a commercial cell phone that transform the phones integrated lens and image sensor into a 350× microscope and visible-light spectrometer. The microscope is capable of transmission and polarized microscopy modes and is shown to have 1.5 micron resolution and a usable field-of-view of 150×150 with no image processing, and approximately 350×350 when post-processing is applied. The spectrometer has a 300 nm bandwidth with a limiting spectral resolution of close to 5 nm. We show applications of the devices to medically relevant problems. In the case of the microscope, we image both stained and unstained blood-smears showing the ability to acquire images of similar quality to commercial microscope platforms, thus allowing diagnosis of clinical pathologies. With the spectrometer we demonstrate acquisition of a white-light transmission spectrum through diffuse tissue as well as the acquisition of a fluorescence spectrum. We also envision the devices to have immediate relevance in the educational field.

Femtosecond X-ray diffraction from two-dimensional protein crystals

Bragg diffraction achieved from two-dimensional protein crystals using femtosecond X-ray laser snapshots is presented.

Nanometer-scale sizing accuracy of particle suspensions on an unmodified cell phone using elastic light scattering.

We report on the construction of a Fourier plane imaging system attached to a cell phone. By illuminating particle suspensions with a collimated beam from an inexpensive diode laser, angularly resolved scattering patterns are imaged by the phones camera. Analyzing these patterns with Mie theory results in predictions of size distributions of the particles in suspension. Despite using consumer grade electronics, we extracted size distributions of sphere suspensions with better than 20 nm accuracy in determining the mean size. We also show results from milk, yeast, and blood cells. Performing these measurements on a portable device presents opportunities for field-testing of food quality, process monitoring, and medical diagnosis.

Polarization coded aperture.

Two examples are presented to illustrate the advantages of polarization coded apertures, in which the incoming light will rotate its polarization at a portion of an aperture. In the first example the depth of field of a diffraction limited lens is increased without sacrificing the light throughput; in the second example the axial focal intensity of a pixelated Fresnel zone plate is increased by 100%. Both examples work for linearly polarized or unpolarized illumination.

Extending the depth of field through unbalanced optical path difference

We describe a simple method to extend the depth of field of a conventional camera by inserting a transparent annular ring in front of the pupil of the lens. The insertion of the ring creates an unbalanced optical path difference across the lens aperture, which partitions the pupil and leads to an extended depth of field. This system is analyzed by diffraction and random process theory. Experiments are reported that are in good agreement with the theory.

Image reconstruction for structured-illumination microscopy with low signal level

We report a new image processing technique for the structured illumination microscopy designed to work with low signals, with the goal of reducing photobleaching and phototoxicity of the sample. Using a pre-filtering process to estimate experimental parameters and total variation as a constraint to reconstruct, we obtain two orders of magnitude of exposure reduction while maintaining the resolution improvement and image quality compared to a standard structured illumination microscopy. The algorithm is validated on both fixed and live cell data with results confirming that we can image more than 15x more time points compared to the standard technique.

Incoherently combining logarithmic aspheric lenses for extended depth of field

We describe a method for combining concentric logarithmic aspheric lenses in order to obtain an extended depth of field. Substantial improvement in extending the depth of field is obtained by carefully controlling the optical path difference among the concentric lenses so that their outputs combine incoherently. The system is analyzed through diffraction theory and the point spread function is shown to be highly invariant over a long range of object distances. After testing the image performance on a three-dimensional scene, we found that the incoherently combined logarithmic aspheres can provide a high-quality image over an axial distance corresponding to a defocus of +/- 14(lambda/4). Studies of the images of two-point objects are presented to illustrate the resolution of these lenses.

Development of inexpensive blood imaging systems: where are we now?

Clinical applications in the developing world, such as malaria and anemia diagnosis, demand a change in the medical paradigm of expensive care given in central locations by highly trained professionals. There has been a recent explosion in optical technologies entering the consumer market through the widespread adoption of smartphones and LEDs. This technology commoditization has enabled the development of small, portable optical imaging systems at an unprecedentedly low cost. Here, we review the state-of-the-field of the application of these systems for low-cost blood imaging with an emphasis on cellular imaging systems. In addition to some promising results addressing specific clinical issues, an overview of the technology landscape is provided. We also discuss several key issues that need to be addressed before these technologies can be commercialized.

Super-resolved spatial light interference microscopy

We report a scheme to achieve resolution beyond the diffraction limit in spatial light interference microscopy (SLIM). By adding a grating to the optical path, the structured illumination technique can be used to improve the resolution by a factor of 2. We show that a direct application of the structured illumination technique, however, has proved to be unsuccessful. Through two crucial modifications, namely, one to the pupil plane of the objective and the other to the demodulation procedure, faithful phase information of the object is recovered and the resolution is improved by a factor of 2.

A modular, open-source, slide-scanning microscope for diagnostic applications in resource-constrained settings

In this paper we report the development of a cost-effective, modular, open source, and fully automated slide-scanning microscope, composed entirely of easily available off-the-shelf parts, and capable of bright field and fluorescence modes. The automated X-Y stage is composed of two low-cost micrometer stages coupled to stepper motors operated in open-loop mode. The microscope is composed of a low-cost CMOS sensor and low-cost board lenses placed in a 4f configuration. The system has approximately 1 micron resolution, limited by the f/# of available board lenses. The microscope is compact, measuring just 25×25×30 cm, and has an absolute positioning accuracy of ±1 μm in the X and Y directions. A Z-stage enables autofocusing and imaging over large fields of view even on non-planar samples, and custom software enables automatic determination of sample boundaries and image mosaicking. We demonstrate the utility of our device through imaging of fluorescent- and transmission-dye stained blood and fecal smears containing human and animal parasites, as well as several prepared tissue samples. These results demonstrate image quality comparable to high-end commercial microscopes at a cost of less than US