Mosaic of Foldscope Images.

<p>Bright field images of (A) <i>Giardia lamblia</i> (2,180X), (B) <i>Leishmania donovani</i> (1,450X), (C) <i>Trypanosoma cruzi</i> (1,450X), (D) gram-negative <i>Escherichia coli</i> (1,450X), (E) gram-positive <i>Bacillus cereus</i> (1,450X), (F) <i>Schistosoma haematobium</i> (140X), and (G) <i>Dirofilaria immitis</i> (140X). Unstained (H) leg muscles and (I) tarsi of an unidentified ladybug (genus <i>Coccinella</i>). (J) Unstained leg muscles (fixed in formaldehyde) of an unidentified red ant (genus <i>Solenopsis</i>). An LED diffuser (Roscolux #111) was added for (A) and an LED condenser (2.4 mm borosilicate ball lens) was used for (C). Images (H–J) were taken by novice user using a self-made Foldscope (140X). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098781#pone-0098781-t002" target="_blank">table 2</a> for ball lenses used for specific magnifications. White scale bar: 5 µm; black scale bar: 100 µm.</p

Foldscope: Origami-Based Paper Microscope

<div><p>Here we describe an ultra-low-cost origami-based approach for large-scale manufacturing of microscopes, specifically demonstrating brightfield, darkfield, and fluorescence microscopes. Merging principles of optical design with origami enables high-volume fabrication of microscopes from 2D media. Flexure mechanisms created via folding enable a flat compact design. Structural loops in folded paper provide kinematic constraints as a means for passive self-alignment. This light, rugged instrument can survive harsh field conditions while providing a diversity of imaging capabilities, thus serving wide-ranging applications for cost-effective, portable microscopes in science and education.</p></div

Foldscope imaging modalities.

<p>(A) Brightfield Foldscope image of a monolayer of 1 µm polystyrene microspheres (Polysciences 07310-15) using a 1,450X lens. (B) Fluorescent Foldscope image of 2 µm polyfluorescent microspheres (Polysciences 19508-2) using a 1,140X lens with Roscolux gel filters #19 and #80. (C) 2X2 lens-array Brightfield Foldscope image of Giemsa-stained thin blood smear using 1,450X lenses. (D) 140X Darkfield Foldscope images of 6 µm polystyrene microspheres (Polysciences 15714-5), using a 140X lens for the darkfield condenser. Darkfield condenser aperture shown in inset has 1.5 mm inner diameter and 4.0 mm outer diameter. (E–H) Schematic cross-sections of Brightfield, Fluorescence, Lens-Array, and Darkfield Foldscope configurations, showing the respective arrangements of ball lenses, filters, and LEDs. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0098781#pone-0098781-t002" target="_blank">table 2</a> for ball lenses used for specific magnifications.</p

Bill of Materials.

<p>Summary of unit costs for Foldscope components in volumes of 10,000 units, not including assembly costs. This assumes a Foldscope in brightfield constructed from the following: polypropylene sheets (Press Sense 10mil Durapro); a 140X low-mag lens (Winsted Precision Ball 2.4 mm borosilicate ball, P/N 3200940F1ZZ00A0, from <a href="http://www.mcmaster.com" target="_blank">www.mcmaster.com</a>, P/N 8996K21) or a 2,180X high-mag lens (Swiss Jewel Co. 0.2 mm sapphire ball lens); a 3V CR2016 button cell (Sanyo CR2016-TT1B #8565 from Batteriesandbutter.com); a white LED (Avago ASMT CW40 from Mouser.com); an electrical slider switch (“Off/On MINI SMD Switch” from AliExpress.com); and copper tape (Sparkfun P/N 76555A648).</p

Manufacturing innovations for lens- and specimen- mounting.

<p>(A) Fabrication, mounting, and characterization of capillary-encapsulation process for lens-mounted apertures. X and Y error bars for all measurements are 2.5 µm. (B) Reel of polystyrene carrier tape with custom pockets and punched holes for mounting over 2,000 ball lenses with optimal apertures. The first ten pockets include mounted ball lenses. Inset shows sectioned view from CAD model of carrier tape mounted lenses. Note the aperture is the punched hole shown on the bottom side of the ball lens. This tape is 16 mm wide and is designed for 2.4 mm ball lenses (aperture diameter is 0.7 mm). (C) <i>Top:</i> Paper microscope slide shown next to standard glass slide with coverslip, both with wet mount algae specimens. <i>Bottom:</i> Schematic of paper microscope slide, showing specimen containment cavity formed between upper tape and lower tape in middle of slide.</p

Analytical, numerical, and empirical characterization of Foldscope.

<p>(A,B) Analytical “design curves” for normalized optimal aperture radius (nOAR) and optimal resolution (RES) versus magnification (MAG) over index of refraction (range 1.33–1.91) and ball lens radius (range 40–1200 µm). (C) Comparison of analytical (3D surface) and numerical (plotted as points) results for RES versus index of refraction and ball lens radius. (D) Modulus of the Optical Transfer Function (MTF) over the optimal field of view for a 300 µm sapphire lens with optimal aperture. (E,F) Image of USAF 1951 resolution target taken with 430X ball lens, including an enlarged caption of Group 9, and an intensity profile plot along path denoted by green line in image caption. This demonstrates resolvability for Group 9, Element 4 corresponding to 724 Line Pairs/mm or 1.38 µm resolution. (G,H) Image of USAF 1951 resolution target taken with 140X ball lens, including an enlarged caption of Group 8, and an intensity profile plot along path denoted by green line in image caption. This demonstrates resolvability for Group 8, Element 6 corresponding to 456 Line Pairs/mm or 2.19 µm resolution. The data was taken using GUPPY Pro 503C scientific camera, with 2592×1944 pixels and pixel size 2.2×2.2 µm².</p

Foldscope Analytical Model Parameter Summary Table.

<p>Functional form and select numerical values for the following dependent parameters: Magnification (MAG), Back Focal Length (BFL), Resolution (RES), nOAR (Normalized Optimal Aperture Radius), OAR (Optimal Aperture Radius), Effective Focal Length (EFL), Numerical Aperture (NA), Field of View (FOV), Depth of Field (DOF), Strehl Ratio (SR). These are calculated for infinite “object” distance per analytical model RM2, with aperture radius , , , and with aberration coefficient . All calculations assume an incident wavelength of λ = 0.55 µm, and all specified distances are in units of µm. The indices of refraction n = 1.517 and n = 1.77 correspond to borosilicate glass and sapphire, respectively.</p

Foldscope design, components and usage.

<p>(A) CAD layout of Foldscope paper components on an A4 sheet. (B) Schematic of an assembled Foldscope illustrating panning, and (C) cross-sectional view illustrating flexure-based focusing. (D) Foldscope components and tools used in the assembly, including Foldscope paper components, ball lens, button-cell battery, surface-mounted LED, switch, copper tape and polymeric filters. (E) Different modalities assembled from colored paper stock. (F) Novice users demonstrating the technique for using the Foldscope. (G) Demonstration of the field-rugged design, such as stomping under foot.</p

Optimisation of a two-liquid component pre-filled acrylic bone cement system: a design of experiments approach to optimise cement final properties

The initial composition of acrylic bone cement along with the mixing and delivery technique used can influence its final properties and therefore its clinical success in vivo. The polymerisation of acrylic bone cement is complex with a number of processes happening simultaneously. Acrylic bone cement mixing and delivery systems have undergone several design changes in their advancement, although the cement constituents themselves have remained unchanged since they were first used. This study was conducted to determine the factors that had the greatest effect on the final properties of acrylic bone cement using a pre-filled bone cement mixing and delivery system. A design of experiments (DoE) approach was used to determine the impact of the factors associated with this mixing and delivery method on the final properties of the cement produced. The DoE illustrated that all factors present within this study had a significant impact on the final properties of the cement. An optimum cement composition was hypothesised and tested. This optimum recipe produced cement with final mechanical and thermal properties within the clinical guidelines and stated by ISO 5833 (International Standard Organisation (ISO), International standard 5833: implants for surgery-acrylic resin cements, 2002), however the low setting times observed would not be clinically viable and could result in complications during the surgical technique. As a result further development would be required to improve the setting time of the cement in order for it to be deemed suitable for use in total joint replacement surgery

Discovery of Novel Dual Mechanism of Action Src Signaling and Tubulin Polymerization Inhibitors (KX2-391 and KX2-361)

The discovery of potent, peptide site directed, tyrosine kinase inhibitors has remained an elusive goal. Herein we describe the discovery of two such clinical candidates that inhibit the tyrosine kinase Src. Compound <b>1</b> is a phase 3 clinical trial candidate that is likely to provide a first in class topical treatment for actinic keratosis (AK) with good efficacy and dramatically less toxicity compared to existing standard therapy. Compound <b>2</b> is a phase 1 clinical trial candidate that is likely to provide a first in class treatment of malignant glioblastoma and induces 30% long-term complete tumor remission in animal models. The discovery strategy for these compounds iteratively utilized molecular modeling, along with the synthesis and testing of increasingly elaborated proof of concept compounds, until the final clinical candidates were arrived at. This was followed with mechanism of action (MOA) studies that revealed tubulin polymerization inhibition as the second MOA