Publications

2017
Deng, S. ; Jwad, T. ; Li, C. ; Benton, D. ; Yetisen, A. K. ; Jiang, K. ; Dai, Q. ; Butt, H. Carbon Nanotube Array Based Binary Gabor Zone Plate Lenses. Scientific Reports 2017, 7 15256. Publisher's VersionAbstract
Diffractive zone plates have a wide range of applications from focusing x-ray to extreme UV radiation. The Gabor zone plate, which suppresses the higher-order foci to a pair of conjugate foci, is an attractive alternative to the conventional Fresnel zone plate. In this work, we developed a novel type of Beynon Gabor zone plate based on perfectly absorbing carbon nanotube forest. Lensing performances of 0, 8 and 20 sector Gabor zone plates were experimentally analyzed. Numerical investigations of Beynon Gabor zone plate configurations were in agreement with the experimental results. A high-contrast focal spot having 487 times higher intensity than the average background was obtained.
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AlQattan, B. ; Benton, D. ; Yetisen, A. K. ; Butt, H. Laser Nanopatterning of Colored Ink Thin Films for Photonic Devices. ACS Applied Materials & Interfaces 2017, 9 39641-39649. Publisher's VersionAbstract
Nanofabrication through conventional methods such as electron beam writing and photolithography is time-consuming, high cost, complex, and limited in terms of the materials which can be processed. Here, we present the development of a nanosecond Nd:YAG laser (532 nm, 220 mJ) in holographic Denisyuk reflection mode method for creating ablative nanopatterns from thin films of four ink colors (black, red, blue, and brown). We establish the use of ink as a recording medium in different colors and absorption ranges to rapidly produce optical nanostructures in 1D geometries. The gratings produced with four different types of ink had the same periodicity (840 nm); however, they produce distant wavelength dependent diffraction responses to monochromatic and broadband light. The nanostructures of gratings consisting of blue and red inks displayed high diffraction efficiency of certain wavelengths while the black and brown ink based gratings diffracted broadband light. These gratings have high potential to be used as low-cost photonic structures in wavelength-dependent optical filters. We anticipate that the rapid production of gratings based on different ink formulations can enable optics applications such as holographic displays in data storage, light trapping, security systems, and sensors.
Jiang, N. ; Butt, H. ; Montelongo, Y. ; Liu, F. ; Afewerki, S. ; Ying, G. L. ; Dai, Q. ; Montelongo, Y. ; Yun, S. H. ; Yetisen, A. K. Laser Interference Lithography for the Nanofabrication of Stimuli-Responsive Bragg Stacks. Advanced Functional Materials. DOI: 10.1002/adfm.201702715 2017. Publisher's VersionAbstract
Dynamic structural coloration in Tmesisternus isabellae beetle elytra is a unique example of Bragg stack-based wavelength tuning in response to external stimuli. The underlying principles could guide the design of quantitative optical stimuli-responsive polymers. Existing nanofabrication techniques to create such materials are costly, time-consuming, and require high expertise. This study reports a nanofabrication method to produce slanted Bragg stack structures in poly(acrylamide-co-poly(ethylene glycol) diacrylate) hydrogel films by combining laser interference lithography and silver halide chemistry in a cost-effective and rapid process (≈10 min). The Bragg stacks consist of silver bromide nanocrystal multilayers having a lattice spacing of ≈200 nm. Upon broadband light illumination, the Bragg stacks diffract a narrow-band peak at 520 nm at ≈10° with respect to the normal incidence. The lattice spacing of the hydrogel films can be modulated by external stimuli to shift the Bragg peak for dynamic quantitative measurements. To demonstrate the utility of this method, the Bragg stacks are functionalized with phenylboronic acid molecules. Bragg peak shift analysis allows reversible glucose sensing within a physiological dynamic range (0.0–20.0 mmol L−1) having a sensitivity of 0.2 mmol L−1. The developed Bragg stacks may have application in portable, wearable, and implantable real-time medical diagnostics at point-of-care settings.
Wavelength-Selective Diffraction from Silica Thin-Film Gratings. ACS Photonics. DOI: 10.1021/acsphotonics.7b00419 2017. Publisher's VersionAbstract
A reflective diffraction grating with a periodic square-wave profile will combine the effects of thin-film interference with conventional grating behavior when composed of features having a different refractive index than that of the substrate. A grating period of 700–1300 nm was modeled and compared for both silicon (Si) and silicon dioxide (SiO2) to determine the behavior of light interaction with the structures. Finite element analysis was used to study nanostructures having a multirefractive index grating and a conventional single material grating. A multimaterial grating has the same diffraction efficiency as that of a grating formed in a single material, but had the advantage of having an ordered relationship between the grating dimensions (thickness and period) and the intensity of reflected and diffracted optical wavelengths. We demonstrate a color-selective feature of the modeled SiO2 grating by fabricating samples with grating periods of 800 and 1000 nm, respectively. A high diffraction efficiency was measured for the green wavelength region as compared to other colors in the spectrum for 800 nm grating periodicity; whereas wavelengths within the red region of spectrum interfered constructively for the grating with 1000 nm periodicity resulting a higher efficiency for red color bandwidth. The results show that diffraction effects can be enhanced by the thin-film interference phenomenon to produce color selective optical devices.
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Alqurashi, T. ; Montelongo, Y. ; Penchev, P. ; Yetisen, A. K. ; Dimov, S. ; Butt, H. Femtosecond laser ablation of transparent microphotonic devices and computer-generated holograms. Nanoscale 2017, 9 13808-13819. Publisher's VersionAbstract
Femtosecond laser ablation allows direct patterning of engineering materials in industrial settings without requiring multistage processes such as photolithography or electron beam lithography. However, femtosecond lasers have not been widely used to construct volumetric microphotonic devices and holograms with high reliability and cost efficiency. Here, a direct femtosecond laser writing process is developed to rapidly produce transmission 1D/2D gratings, Fresnel Zone Plate lenses, and computer-generated holograms. The optical properties including light transmission, angle-dependent resolution, and light polarization effects for the microphotonic devices have been characterized. Varying the depth of the microgratings from 400 nm to 1.5 μm allowed the control over their transmission intensity profile. The optical properties of the 1D/2D gratings were validated through a geometrical theory of diffraction model involving 2D phase modulation. The produced Fresnel lenses had transmission efficiency of ∼60% at normal incidence and they preserved the polarization of incident light. The computer-generated holograms had an average transmission efficiency of 35% over the visible spectrum. These microphotonic devices had wettability resistance of contact angle ranging from 44° to 125°. These devices can be used in a variety of applications including wavelength-selective filters, dynamic displays, fiber optics, and biomedical devices.
Dou, Q. ; Hu, D. ; Gao, H. ; Zhang, Y. ; Yetisen, A. K. ; Butt, H. ; Wang, J. ; Nie, G. ; Dai, Q. High performance boronic acid-containing hydrogel for biocompatible continuous glucose monitoring. RSC Advances 2017, 7 41384-41390. Publisher's VersionAbstract
Rapid and robust hydrogels are essential in realizing continuous glucose monitoring in diabetes monitoring. However, existing hydrogels are limited in satisfying all of the sensory requirements such as detection range, response time, recoverability and biocompatibility. Here, we have developed a surface-initiated polymerization method to chemically immobilize a nano-boronic acid-hydrogel membrane onto a quartz crystal, then used a quartz crystal microbalance (QCM) to achieve real-time monitoring of glucose. The experimental results show that this hydrogel possesses enhanced binding properties to glucose under physiological conditions (pH 7.0–7.5) and blood glucose concentration (BGC) (1.1–33.3 mM). Moreover, our hydrogel displayed a rapid response time (∼100 s) to glucose, high biocompatibility in vivo through an animal model. The hydrogel has a great potential as a sensitive glucose probe for implantable continuous glucose sensors.
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Bentaleb, E. M. ; Messaoudi, M. D. E. ; Abid, M. ; Messaoudi, M. ; Yetisen, A. K. ; Sefrioui, H. ; Amzazi, S. ; Benhassou, H. A. Plasmid-based High-Resolution Melting Analysis for Rapid Detection of rpoB Mutations in Mycobacterium tuberculosis Isolates from Moroccan Patients. BMC Infectious Diseases 2017, 17, 548.Abstract

Background

Rapid diagnosis of drug resistance in tuberculosis (TB) is pivotal for the timely initiation of effective antibiotic treatment to prevent the spread of drug-resistant strains. The development of low-cost, rapid and robust methods for drug-resistant TB detection is highly desirable for resource-limited settings.

Methods

We report the use of an in house plasmid-based quantitative polymerase chain reaction-high-resolution melting (qPCR-HRM) analysis for the detection of mutations related to rifampicin-resistant Mycobacterium tuberculosis (MTB) in clinical isolates from Moroccan patients. Five recombinant plasmids containing predominant mutations (S531L, S531W, H526Y and D516V) and the wild-type sequence of the Rifampicin Resistance-Determining Region (RRDR) have been used as controls to screen 45 rifampicin-resistant and 22 rifampicin-susceptible MTB isolates.

Results

The sensitivity and the specificity of the qPCR-HRM analysis were 88.8% and 100% respectively as compared to rifampicin Drug Susceptibility Testing (DST). The results of qPCR-HRM and DNA sequencing had a concordance of 100%.

Conclusion

Our qPCR-HRM assay is a sensitive, accurate and cost-effective assay for the high-throughput screening of mutation-based drug resistance in TB reference laboratories.

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Vega, K. ; Jiang, N. ; Kan, V. ; Liu, X. ; Barry, N. ; Maes, P. ; Yetisen, A. K. ; Paradiso, J. The Dermal Abyss: Interfacing with the Skin by Tattooing Biosensors. ISWC2017 2017, 138-145. Publisher's VersionAbstract
The Dermal Abyss (d-abyss) presents an approach to biointerfaces in which the body surface is rendered as an interactive display by patterning biosensors into the skin to produce color changes in response to biomarker variations in the interstitial fluid. It combines advances in biotechnology with traditional methods in tattoo artistry. d-abyss is designed to use the aesthetics, permanence, and visible nature of tattoos to encode information. In the present work, we replace traditional inks with colorimetric and fluorescent biosensors that can report on the concentration of sodium, glucose, and pH in the interstitial fluid of the skin. We report the preliminary evaluation of these biosensors in an ex vivo skin model, assessing their visibility from the dermis. We describe different applications of d-abyss in the medical, lifestyle, and security domains. This work is a proof of concept of a platform in which the skin reveals information inside the body, tattoos form wearable displays within the skin, and the body’s metabolism works as an input for the d-abyss biosensors.
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Tamayol, A. ; Najafabadi, A. H. ; Mostafalu, P. ; Memic, A. ; Yetisen, A. K. ; Commotto, M. ; Aldhaheri, M. ; Shaban, M. ; Annabi, N. ; Yun, S. H. ; et al. Biodegradable elastic nanofibrous platforms with integrated flexible heaters for on-demand drug delivery. Scientific Reports 2017, 7 9220.Abstract
Delivery of drugs with controlled temporal profiles is essential for wound treatment and regenerative medicine applications. For example, bacterial infection is a key challenge in the treatment of chronic and deep wounds. Current treatment strategies are based on systemic administration of high doses of antibiotics, which result in side effects and drug resistance. On-demand delivery of drugs with controlled temporal profile is highly desirable. Here, we have developed thermally controllable, antibiotic-releasing nanofibrous sheets. Poly(glycerol sebacate)- poly(caprolactone) (PGS-PCL) blends were electrospun to form elastic polymeric sheets with fiber diameters ranging from 350 to 1100 nm and substrates with a tensile modulus of approximately 4-8 MPa. A bioresorbable metallic heater was patterned directly on the nanofibrous substrate for applying thermal stimulation to release antibiotics on-demand. In vitro studies confirmed the platform’s biocompatibility and biodegradability. The released antibiotics were potent against tested bacterial strains. These results may pave the path toward developing electronically controllable wound dressings that can deliver drugs with desired temporal patterns.
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Ahmed, R. ; Rifat, A. A. ; Hassan, M. U. ; Yetisen, A. K. ; Butt, H. Phase-conjugated directional diffraction from a retroreflector array hologram. RSC Advances 2017, 7 25657-25664. Publisher's VersionAbstract

A corner cube retroreflector (CCR) consists of three perpendicular flat surfaces and reflects the incident light back to its source. Optical properties of CCR arrays have applications in free space optical communication, low power wireless networks and sensing applications. Conventional top-down CCR array fabrication is complex and requires expensive equipment and limited to broadband reflection only. Here, we utilize laser assisted copying of a CCR array to a light sensitive holography polymer film (∼10 μm) which was placed parallel to the object plane (CCR array) during the recording. Optical characterization of the recorded CCR array hologram was carried out using reflection and color-selective diffraction measurements. Angle dependent optical properties were also simulated computationally followed by their experimental realization, which confirm our experimental findings. In a broadband illumination setting, a broadband white light reflection and a narrowband color diffraction were observed. A linear relationship between the incidence angle of the broadband light and the diffraction angle of the diffracted color light was observed. Bright and well-defined 2nd order far-field diffraction patterns were observed using an image-screen experiment. Maximum diffraction efficiency (DE) of ∼50% was observed for the monochromatic green light at normal illumination setting. The far-field diffraction interspacing/intensity exhibits increasing/decreasing trend with illumination tilt angles, measured between 10 to 50 degrees. The recorded CCR array holograms offer potential applications in color selective diffraction optics and customized optical devices.

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Alqurashi, T. ; Sabouri, A. ; Penchev, P. ; Yetisen, A. K. ; Dimov, S. ; Butt, H. Femtosecond Laser Directed Fabrication of Optical Diffusers. RSC Advances 2017, 7 18019-18023. Publisher's VersionAbstract

Optical diffusers are widely used in filament lamps, imaging systems, display technologies, lasers, and Light Emitting Diodes (LEDs). Here, a method for the fabrication of optical diffusers through femtosecond laser machining is demonstrated. Float glass surfaces were ablated with femtosecond laser light to form nanoscale ripples with dimensions comparable to the wavelength of visible light. These structures produce highly efficient and wide field of view diffusers. The machined patterns altered the average surface roughness, with the majority of particles in the range of a few hundred nanometers. The optical diffusion characteristic and a maximum diffusion angle of near 172° was achieved with optimum machining parameters. The transmission performance of the diffusers was measured to be ∼30% across the visible spectrum. The demonstrated technique has potential for producing low-cost large area optical devices. The process benefits from the flexibility of the laser writing method and enables the production of custom optical diffusers.

Deng, S. ; Butt, H. ; Jiang, K. ; Dlubak, B. ; Kidambi, P. R. ; Seneor, P. ; Xavier, S. ; Yetisen, A. K. Graphene Nanoribbons Based Plasmonic Fresnel Zone Plate Lenses. RSC Advances 2017, 7 16594-16601. Publisher's VersionAbstract

A graphene-based metamaterial lens is theoretically proposed by combining plasmonic nanoribbons with Fresnel Zone Plate (FZP) architecture to realize wavelength-selective and tunable lensing. The plasmonic FZP lens shows higher focal intensity and efficiency compared to conventional FZP. As compared with normal graphene FZP, the lensing effect of the plasmonic FZP can be enhanced by 83 times. When compared with Au thin film based FZP lenses, the graphene plasmonic lenses can achieve comparable lensing effects, but with a thinner geometry and with an additional advantage of being wavelength selective and tuneable. The analyses of selectivity and tunability of the plasmonic lens show that the plasmonic lens functions as a filter with broadband incident light or as a switch which can be turned on and off via changing the Fermi levels. The diffraction between neighboring graphene nanoribbons and the effect of the substrate on the lensing effect is also discussed. The plasmonic effect of the nanoribbons only contributes to the focal intensity without affecting the diffraction properties of Fresnel zone plate lenses such as focal lengths. This plasmonic FZP lens is an ideal combination of near and far field optics. However, the complex interaction of diffractions within and between the FZP rings could lead to a significant change of the lensing effect, which opens the possibility of creating innovative graphene metamaterial devices. The findings in this work can be used for developing wavelength-selective electro-optical applications operating in the infrared and terahertz ranges.

 

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Alqurashi, T. ; Sabouri, A. ; Yetisen, A. K. ; Butt, H. Nanosecond Pulsed Laser Texturing of Optical Diffusers. AIP Advances 2017, 7 025313. Publisher's VersionAbstract

High-quality optical glass diffusers have applications in aerospace, displays, imaging systems, medical devices, and optical sensors. The development of rapid and accurate fabrication techniques is highly desirable for their production. Here, a micropatterning method for the fast fabrication of optical diffusers by means of nanosecond pulsed laser ablation is demonstrated (λ=1064 nm, power=7.02, 9.36 and 11.7 W and scanning speed=200 and 800 mm s-1). The experiments were carried out by point-to-point texturing of a glass surface in spiral shape. The laser machining parameters, the number of pulses and their power had significant effect on surface features. The optical characteristics of the diffusers were characterized at different scattering angles. The features of the microscale structures influenced average roughness from 0.8 μm to 1.97 μm. The glass diffusers scattered light at angles up to 20° and their transmission efficiency were measured up to ∼97% across the visible spectrum. The produced optical devices diffuse light less but do so with less scattering and energy losses as compared to opal diffusing glass. The presented fabrication method can be applied to any other transparent material to create optical diffusers. It is anticipated that the optical diffusers presented in this work will have applications in the production of LED spotlights and imaging devices.

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Ahmed, R. ; Yetisen, A. K. ; Butt, H. High Numerical Aperture Hexagonal Stacked Ring-Based Bidirectional Flexible Polymer Microlens Array. ACS Nano 2017, 11, 3155-3165. Publisher's VersionAbstract

Flexible imprinted photonic nanostructures that are able to diffract/focus narrow-band light have potential applications in optical lenses, filters, tunable lasers, displays, and biosensing. Nanophotonic structures through holography and roll-to-roll printing may reduce fabrication complexities and expenses and enable mass production. Here, 3D photonic nanostructures of a stacked ring array were imprinted on acrylate polymer (AP) over poly(ethylene terephthalate) (PET) substrate through holography and lift-off processes to create a microlens array (MLA). The surface structure of the array consisted of circular nonostepped pyramids, and repeated patterns were in hexagonal arrangements. Stacked-ring-based MLA (SMLA) on a flexible AP–PET substrate showed efficient bidirectional light focusing and maximum numerical aperture (NA = 0.60) with a reasonable filling factor. The nanostructures produced a well-ordered hexagonally focused diffraction pattern in the far field, and power intensities were measured through angle-resolved experiments. The variation of nanostep dimensions (width and height) and the number of steps resulted in different photonic bandgaps, and the arrays produced distance-dependent narrow-band light focusing. The validation of the SMLA was demonstrated through the text, image, and hologram projection experiments. It is anticipated that imprinted bidirectional SMLA over flexible substrates may find applications in optical systems, displays, and portable sensors.

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Sabouri, A. ; Yetisen, A. ; Sadigzade, R. ; Hassanin, H. ; Essa, K. ; Butt, H. Three-Dimensional Microstructured Lattices for Oil Sensing. Energy & Fuels 2017, 31, 2524-2529. Publisher's VersionAbstract

Monitoring of environmental contamination, including oil pollution, is important to protect marine ecosystems. A wide range of sensors are used in the petroleum industry to measure various parameters, such as viscosity, pressure, and flow. Here, we create an optical lattice mesh structure that can be used as an oil sensor integrated with optical fiber probing. The principle of operation of the sensor was based on light scattering, where the tested medium acted as a diffuser. Three different mesh-patterned structures were analyzed by optical imaging, light transmission, and scattering in the presence of supercut, diesel, and stroke oil types. The meshes were used as a medium for different types of oils, and the optical diffusion and transmission were studied in the visible spectrum. Angle-resolved measurements were carried out to characterize the light scattering behavior from the mesh structures. Different types of oils were identified on the basis of the optical behavior of the lattice structure. The fabricated mesh structures can be used as a low-cost measurement device in oil sensing.

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Yetisen, A. K. ; Jiang, N. ; Fallahi, A. ; Montelongo, Y. ; Ruiz-Esparza, G. U. ; Tamayol, A. ; Zhang, Y. S. ; Mahmood, I. ; Yang, S. A. ; Kim, K. S. ; et al. Glucose-Sensitive Hydrogel Optical Fibers Functionalized with Phenylboronic Acid. Advanced Materials 2017, 29, 1606380. Publisher's VersionAbstract

Hydrogel optical fibers are utilized for continuous glucose sensing in real time. The hydrogel fibers consist of poly(acrylamide-co-poly(ethylene glycol) diacrylate) cores functionalized with phenylboronic acid. The complexation of the phenylboronic acid and cis-diol groups of glucose enables reversible changes of the hydrogel fiber diameter. The analyses of light propagation loss allow for quantitative glucose measurements within the physiological range.

Yetisen, A. K. ; Jiang, N. ; Ruiz-Esparza, G. U. ; Gupta, A. ; Medina-Pando, S. ; Tamayol, A. ; Zhang, Y. S. ; Wolffsohn, J. S. ; Butt, H. ; Khademhosseini, A. ; et al. Paper-Based Microfluidic System for Tear Electrolyte Analysis. Lab on a Chip 2017, 17, 1137-1148. Publisher's VersionAbstract

The analysis of tear constituents at point-of-care settings has a potential for early diagnosis of ocular disorders such as dry eye disease, low-cost screening, and surveillance of at-risk subjects. However, current minimally-invasive rapid tear analysis systems for point-of-care settings have been limited to assessment of osmolarity or inflammatory markers and cannot differentiate between dry eye subclassifications. Here, we demonstrate a portable microfluidic system that allows quantitative analysis of electrolytes in the tear fluid that is suited for point-of-care settings. The microfluidic system consists of a capillary tube for sample collection, a reservoir for sample dilution, and a paper-based microfluidic device for electrolyte analysis. The sensing regions are functionalized with fluorescent crown ethers, o-acetanisidide, and seminaphtorhodafluor that are sensitive to mono- and divalent electrolytes, and their fluorescence outputs are measured with a smartphone readout device. The measured sensitivity values of Na+, K+, Ca2+ ions and pH in artificial tear fluid were matched with the known ion concentrations within the physiological range. The microfluidic system was tested with samples having different ionic concentrations, demonstrating the feasibility for the detection of early-stage dry eye, differential diagnosis of dry eye sub-types, and their severity staging.

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Ahmed, R. ; Yetisen, A. K. ; El Khoury, A. ; Butt, H. Printable Ink Lenses, Diffusers, and 2D Gratings. Nanoscale 2017, 9 266-276. Publisher's VersionAbstract

Advances in holography have led to applications including data storage, displays, security labels, and colorimetric sensors. However, existing top-down approaches for the fabrication of holographic devices are complex, expensive, and expertise dependent, limiting their use in practical applications. Here, ink-based holographic devices have been created for a wide range of applications in diffraction optics. A single pulse of a 3.5 ns Nd:YAG laser allowed selective ablation of ink to nanofabricate planar optical devices. The practicality of this method is demonstrated by fabricating ink-based diffraction gratings, 2D holographic patterns, optical diffusers, and Fresnel zone plate (FZP) lenses by using the ink. The fabrication processes were rationally designed using predictive computational modeling and the devices were fabricated within a few minutes demonstrating amenability for large scale printable optics through industrial manufacturing. It is anticipated that ink will be a promising diffraction optical material for the rapid printing of low-cost planar nanophotonic devices.

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Butt, H. ; Yetisen, A. K. ; Khan, A. A. ; Knowles, K. ; Malik, Q. ; Yun, S. H. ; Wilkinson, T. D. Electrically Tunable Scattering from Devitrite-Liquid Crystal Hybrid Devices. Advanced Optical Materials 2017, 5 1600414. Publisher's VersionAbstract

Devitrite is normally an unwanted crystalline impurity in the soda-lime-silica glass making process. Thin needles formed by heterogeneous nucleation of devitrite on the glass surface provide unique birefringence properties for potential applications in tunable optical devices. Here, devitrite and a liquid crystal are combined to create an electrically variable optical diffuser. The magnitude and scattering angle of the transmitted light propagating through the diffuser are tuned by varying the voltage between the graphene and indium tin oxide electrodes on either side of the liquid crystal. The threshold voltage to switch the transmitted light from a predominantly horizontal diffusion to a random order is 3.5 V. Angle-resolved measurements show broad diffusion angles of transmitted light with a maximum deflection of ±60°. The dynamically tunable devitrite-liquid crystal hybrid devices may advance the development of currently less viable technologies including beam shaping and automatic light transmission control.

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Brinegar, K. ; Yetisen, A. K. ; Choi, S. ; Vallillo, E. ; Ruiz-Esparza, G. U. ; Prabhakar, A. M. ; Khademhosseini, A. ; Yun, S. H. The Commercialization of Genome Editing Technologies. Critical Reviews in Biotechnology 2017, 1-12. Publisher's VersionAbstract

The emergence of new gene-editing technologies is profoundly transforming human therapeutics, agriculture, and industrial biotechnology. Advances in clustered regularly interspaced short palindromic repeats (CRISPR) have created a fertile environment for mass-scale manufacturing of cost-effective products ranging from basic research to translational medicine. In our analyses, we evaluated the patent landscape of gene-editing technologies and found that in comparison to earlier gene-editing techniques, CRISPR has gained significant traction and this has established dominance. Although most of the gene-editing technologies originated from the industry, CRISPR has been pioneered by academic research institutions. The spinout of CRISPR biotechnology companies from academic institutions demonstrates a shift in entrepreneurship strategies that were previously led by the industry. These academic institutions, and their subsequent companies, are competing to generate comprehensive intellectual property portfolios to rapidly commercialize CRISPR products. Our analysis shows that the emergence of CRISPR has resulted in a fivefold increase in genome-editing bioenterprise investment over the last year. This entrepreneurial movement has spurred a global biotechnology revolution in the realization of novel gene-editing technologies. This global shift in bioenterprise will continue to grow as the demand for personalized medicine, genetically modified crops and environmentally sustainable biofuels increases. However, the monopolization of intellectual property, negative public perception of genetic engineering and ambiguous regulatory policies may limit the growth of these market segments.

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