Evaluation of the LeukoScope for Point-of-Care Measurement of White Blood Cell and Neutrophil Counts in Malawi.

White blood cell (WBC) and neutrophil counts are important laboratory tests used by clinicians to assess a variety of conditions. However, current methods to measure WBC and neutrophil counts are difficult to perform at the point of care, being either cost or labor prohibitive. To meet this need, we developed the LeukoScope: a portable, imaging-based system to measure WBC and neutrophil counts from a drop of blood.

Clinical training and validation of the LeukoScope: a low-cost, point-of-care device to perform white blood cell and neutrophil counts.

A white blood cell (WBC) count with partial differential is an important clinical laboratory test. However, current methods to perform a WBC count and differential are difficult to use at the point of care or too expensive for use in low-resource settings. To meet this need, we developed the LeukoScope: a low-cost system to measure a WBC and neutrophil count from a single drop of blood at the point of care.

A Dye-Free Analog to Retinal Angiography Using Hyperspectral Unmixing to Retrieve Oxyhemoglobin Abundance.

Purpose: Retinal angiography evaluates retinal and choroidal perfusion and vascular integrity and is used to manage many ophthalmic diseases, such as age-related macular degeneration. The most common method, fluorescein angiography (FA), is invasive and can lead to untoward effects. As an emerging replacement, noninvasive OCT angiography (OCTA) is used regularly as a dye-free substitute with superior resolution and additional depth-sectioning abilities; however, general trends in FA as signified by varying intensity in images are not always reproducible in the fine structural detail in an OCTA image stack because of the source of their respective signals, OCT speckle decorrelation versus fluorescein emission.

Light-guide snapshot imaging spectrometer for remote sensing applications.

A fiber-based snapshot imaging spectrometer was developed with a maximum of 31853 (~188 x 170) spatial sampling and 61 spectral channels in the 450nm-750nm range. A compact, custom-fabricated fiber bundle was used to sample the object image at the input and create void spaces between rows at the output for dispersion. The bundle was built using multicore 6x6 fiber block ribbons.

Simple ultraviolet microscope using off-the-shelf components for point-of-care diagnostics.

At the primary care setting, where there are often no or minimal laboratories, examinations often consist of self-testing and rapid diagnostics. Because of this, medical devices must be simple, robust, and easy to operate. To address these concerns, an alternate fluorescence microscope design uses ultraviolet (UV) excitation, since fluorescent dyes that are excitable in the visible region are also excitable by UV.

High-resolution endomicroscopy with a spectrally encoded miniature objective.

Fiber bundle endomicroscopy techniques have been used for numerous minimally invasive imaging applications. However, these techniques may provide limited spatial sampling due to the limited number of imaging cores inside the fiber bundle. Here, we present a custom-fabricated miniature objective that can be coupled to a fiber bundle and can overcome the fiber bundle's sampling threshold by utilizing the spectral encoding concept.

High performance image mapping spectrometer (IMS) for snapshot hyperspectral imaging applications.

A high performance, snapshot Image Mapping Spectrometer was developed that provides fast image acquisition (100 Hz) of 16 bit hyperspectral data cubes (210x210x46) over a spectral range of 515-842 nm. Essential details of the opto-mechanical design are presented. Spectral accuracy, precision, and image reconstruction metrics such as resolution are discussed.

3D printed fiber optic faceplates by custom controlled fused deposition modeling.

A 3D printing technique for manufacturing air-clad coherent fiber optic faceplates is presented. The custom G-code programming is implemented on a fused deposition modeling (FDM) desktop printer to additively draw optical fibers using high-transparency thermoplastic filaments. The 3D printed faceplate consists of 20000 fibers and achieves spatial resolution 1.

Development of a universal, tunable, miniature fluorescence microscope for use at the point of care.

Fluorescence microscopy can be a powerful tool for cell-based diagnostic assays; however, imaging can be time consuming and labor intensive to perform. Tunable systems give the ability to electronically focus at user selected depths inside an object volume and may simplify the opto-mechanical design of the imaging system. We present a prototype of a universal, tunable, miniature fluorescence microscope built from poly(methyl methacrylate) singlets that incorporates miniature, electrowetted lenses for electronic focusing.

High spatial sampling light-guide snapshot spectrometer.

A prototype fiber-based imaging spectrometer was developed to provide snapshot hyperspectral imaging tuned for biomedical applications. The system is designed for imaging in the visible spectral range from 400 to 700 nm for compatibility with molecular imaging applications as well as satellite and remote sensing. An 81 × 96 pixel spatial sampling density is achieved by using a custom-made fiber-optic bundle.

Quantitative evaluation of performance of 3D printed lenses.

We present an analysis of the shape, surface quality, and imaging capabilities of custom 3D printed lenses. 3D printing technology enables lens prototypes to be fabricated without restrictions on surface geometry. Thus, spherical, aspherical and rotationally non-symmetric lenses can be manufactured in an integrated production process.

Differentiating between live and dead Mycobacterium smegmatis using autofluorescence.

While there have been research efforts to find faster and more efficient diagnostic techniques for tuberculosis (TB), it is equally important to monitor a patient's response to treatment over time, especially with the increasing prevalence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) TB. Between sputum smear microscopy, culture, and GeneXpert, only culture can verify viability of mycobacteria. However, it may take up to six weeks to grow Mycobacterium tuberculosis (Mtb), during which time the patient may have responded to treatment or the mycobacteria are still viable because the patient has MDR or XDR TB.

Hyperspectral Image Mapping Spectrometry for Retinal Oximetry Measurements in Four Diseased Eyes.

We describe the hyperspectral Image Mapping Spectrometer (IMS) which is able to acquire spectral images of the retina with no scanning components. We then utilize this technology to obtain absolute oxygen saturation measurements in four patients with retinal diseases. The IMS acquires spatial and spectral information of a scene in a single camera exposure time.

Development of tunable miniature piezoelectric-based scanners validated by the combination of two scanners in a direct image relay technique.

Miniature piezoelectric actuators are commonly used as a compact means to relay images for numerous endoscopic applications. These scanners normally consist of an electrically driven lead zirconate titanate (PZT) tube that oscillates an optical fiber at its resonant frequency. The diameter and length of the PZT and fiber, the attachment of the fiber to the PZT, as well as the driving signal determine the main characteristics of the scan-frequency and amplitude of vibration.

All-plastic, miniature, digital fluorescence microscope for three part white blood cell differential measurements at the point of care.

Three-part differential white blood cell counts are used for disease diagnosis and monitoring at the point-of-care. A low-cost, miniature achromatic microscope was fabricated for identification of lymphocytes, monocytes, and granulocytes in samples of whole blood stained with acridine orange. The microscope was manufactured using rapid prototyping techniques of diamond turning and 3D printing and is intended for use at the point-of-care in low-resource settings.

All-plastic miniature fluorescence microscope for point-of-care readout of bead-based bioassays.

A number of new platforms have been developed for multiplexed bioassays that rely on imaging targeted fluorescent beads labeled with different fluorescent dyes. We developed a compact, low-cost three-dimensional printed fluorescence microscope that can be used as a detector for mutiplexed, bead-based assays to support point-of-care applications. Images obtained with the microscope were analyzed to differentiate multiple analytes in a single sample with a comparable limit of detection to commercially available macroscopic assay platforms.

Miniature, minimally invasive, tunable endoscope for investigation of the middle ear.

We demonstrate a miniature, tunable, minimally invasive endoscope for diagnosis of the auditory system. The probe is designed to sharply image anatomical details of the middle ear without the need for physically adjusting the position of the distal end of the endoscope. This is achieved through the addition of an electrowetted, tunable, electronically-controlled lens to the optical train.

Low-Cost Disposable Cartridge for Performing a White Blood Cell Count and Partial Differential at the Point-of-Care.

Being able to perform a white blood cell (WBC) count and differential is a crucial laboratory test for basic diagnostic practices. In this paper, we demonstrate proof of concept results for a disposable cartridge that could be used to perform a WBC count and 3-part differential at the point-of-care. The cartridge is composed of a glass slide, a layer of transfer tape, and a glass cover slip and incorporates acridine orange for cell staining and sub-type differentiation; the stained blood is then imaged, and image analysis techniques return a WBC count and 3-part differential.