Novel Deposition Method of Crosslinked Polyethylene Thin Film for Low-Refractive-Index Mid-Infrared Optical Coatings.

Mid-infrared optics require optical coatings composed of high- and low-refractive-index dielectric layers for the design of optical mirrors, filters, and anti-reflection coatings. However, there are not many technologies for depositing a material with a refractive index of less than 2 and a low loss in the mid-infrared region. Here, we present a unique deposition method of crosslinked polyethylene thin film for mid-IR optical filter design. Polyethylene has a refractive index of 1.52 in the mid-infrared region and a small number of absorption peaks, so it is useful for making optical filters in the mid-infrared region. Only 1 keV of energy is required to crosslink the entire film by irradiating an electron beam while depositing polyethylene. In addition, crosslinked polyethylene thin film has high mechanical strength, so there is no cracking or peeling when used with germanium. This allows for the use of crosslinked polyethylene as a low refractive index for mid-infrared optical coating.

Plasma-Etched Pattern Transfer of Sub-10 nm Structures Using a Metal-Organic Resist and Helium Ion Beam Lithography.

Field-emission devices are promising candidates to replace silicon fin field-effect transistors as next-generation nanoelectronic components. For these devices to be adopted, nanoscale field emitters with nanoscale gaps between them need to be fabricated, requiring the transfer of, for example, sub-10 nm patterns with a sub-20 nm pitch to substrates like silicon and tungsten. New resist materials must therefore be developed that exhibit the properties of sub-10 nm resolution and high dry etch resistance. A negative tone, metal-organic resist is presented here. It can be patterned to produce sub-10 nm features when exposed to helium ion beam lithography at line doses on the order of tens of picocoulombs per centimeter. The resist was used to create 5 nm wide, continuous, discrete lines spaced on a 16 nm pitch in silicon and 6 nm wide lines on an 18 nm pitch in tungsten, with line edge roughness of 3 nm. After the lithographic exposure, the resist demonstrates high resistance to silicon and tungsten dry etch conditions (SF6 and C4F8 plasma), allowing the pattern to be transferred to the underlying substrates. The resist's etch selectivity for silicon and tungsten was measured to be 6.2:1 and 5.6:1, respectively; this allowed 3 to 4 nm thick resist films to yield structures that were 21 and 19 nm tall, respectively, while both maintained a sub-10 nm width on a sub-20 nm pitch.

Use of Supramolecular Assemblies as Lithographic Resists.

A new resist material for electron beam lithography has been created that is based on a supramolecular assembly. Initial studies revealed that with this supramolecular approach, high-resolution structures can be written that show unprecedented selectivity when exposed to etching conditions involving plasmas.

Silicon-on-insulator-based complementary metal oxide semiconductor integrated optoelectronic platform for biomedical applications.

Microscale optical devices enabled by wireless power harvesting and telemetry facilitate manipulation and testing of localized biological environments (e.g., neural recording and stimulation, targeted delivery to cancer cells). Design of integrated microsystems utilizing optical power harvesting and telemetry will enable complex in vivo applications like actuating a single nerve, without the difficult requirement of extreme optical focusing or use of nanoparticles. Silicon-on-insulator (SOI)-based platforms provide a very powerful architecture for such miniaturized platforms as these can be used to fabricate both optoelectronic and microelectronic devices on the same substrate. Near-infrared biomedical optics can be effectively utilized for optical power harvesting to generate optimal results compared with other methods (e.g., RF and acoustic) at submillimeter size scales intended for such designs. We present design and integration techniques of optical power harvesting structures with complementary metal oxide semiconductor platforms using SOI technologies along with monolithically integrated electronics. Such platforms can become the basis of optoelectronic biomedical systems including implants and lab-on-chip systems.

Metawaveguide for Asymmetric Interferometric Light-Light Switching.

Light-light switching typically requires strong nonlinearity where intense laser fields route and direct data flows of weak power, leading to a high power consumption that limits its practical use. Here we report an experimental demonstration of a metawaveguide that operates exactly in the opposite way in a linear regime, where an intense laser field is interferometrically manipulated on demand by a weak control beam with a modulation extinction ratio up to approximately 60 dB. This asymmetric control results from operating near an exceptional point of the scattering matrix, which gives rise to intrinsic asymmetric reflections of the metawaveguide through delicate interplay between index and absorption. The designed metawaveguide promises low-power interferometric light-light switching for the next generation of optical devices and networks.

Experimental realization of Bloch oscillations in a parity-time synthetic silicon photonic lattice.

As an important electron transportation phenomenon, Bloch oscillations have been extensively studied in condensed matter. Due to the similarity in wave properties between electrons and other quantum particles, Bloch oscillations have been observed in atom lattices, photonic lattices, and so on. One of the many distinct advantages for choosing these systems over the regular electronic systems is the versatility in engineering artificial potentials. Here by utilizing dissipative elements in a CMOS-compatible photonic platform to create a periodic complex potential and by exploiting the emerging concept of parity-time synthetic photonics, we experimentally realize spatial Bloch oscillations in a non-Hermitian photonic system on a chip level. Our demonstration may have significant impact in the field of quantum simulation by following the recent trend of moving complicated table-top quantum optics experiments onto the fully integrated CMOS-compatible silicon platform.

Optical power transfer and communication methods for wireless implantable sensing platforms.

Ultrasmall scale implants have recently attracted focus as valuable tools for monitoring both acute and chronic diseases. Semiconductor optical technologies are the key to miniaturizing these devices to the long-sought sub-mm scale, which will enable long-term use of these devices for medical applications. This can also enable the use of multiple implantable devices concurrently to form a true body area network of sensors. We demonstrate optical power transfer techniques and methods to effectively harness this power for implantable devices. Furthermore, we also present methods for optical data transfer from such implants. Simultaneous use of these technologies can result in miniaturized sensing platforms that can allow for large-scale use of such systems in real world applications.

A multiplex PCR assay for the simultaneous detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.

INTRODUCTION: For developing countries, sexually transmitted infections (STIs) and their complications are ranked in the top 5 disease categories for which adults seek medical treatment. Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) are the three most common STIs worldwide, with TV accounting for over half of the cases. In developing countries, traditional methods for diagnosing STIs are laborious, often not very sensitive, and have a long turnaround time with most recent commercially available diagnostic tests targeting one or, at most, two of these STIs at a time. Here, we describe the development of a highly sensitive, rapid and affordable sample-to-answer multiplex PCR-based assay for the simultaneous detection of Trichomonas vaginalis, Neisseria gonorrhoeae, and Chlamydia trachomatis. MATERIALS AND METHODS: We designed a multiplex PCR assay for the detection of 4 targets (CT, TV, NG, and process/PCR control) using melt curve analysis. To establish the limit of detection (LOD) for each pathogen, we used previously extracted and quantified TV, NG, and CT genomic DNA (Vircell, Spain). For each target, the LOD was determined by lowering its copy number while increasing the other two STI loads in a stepwise fashion. The process/PCR control remained constant in the optimized assay and was spiked into each sample before extraction. For a concordance study, we tested urine, vaginal and rectal swab specimens from 26 patients positive for one or more of the tested STIs. In addition, 56 liquid cytology specimens (Thinprep) were used to assess specificity. RESULTS: This assay has a turnaround time of less than 2h and has a limit of detection as low as 7-31 copies for each STI in the presence of the other 2 targets. Our assay also demonstrated 100% concordance with 26 known clinical samples from urine, vaginal and rectal swab specimens. TV, NG, CT, and our process/PCR control were consistently identified at 78°C, 82.3°C, 85.7°C, and ~92°C, respectively. When applied to DNA extracted from residual Thinprep specimens, the assay was negative in 54/56 samples. Two samples were found to be co-infected with CT. CONCLUSIONS: Our multiplex assay combines a rapid and cost-effective approach to molecular diagnostics with the versatility required for use within a variety of laboratory settings. These performance characteristics make this multiplex STI assay highly suitable for use in a clinical laboratory.

A rapid RT-PCR assay for the detection of HIV-1 in human plasma specimens.

INTRODUCTION: The CDC estimates that there are currently over 1million people living with human immunodeficiency virus (HIV-1) in the United States, with new cases increasing by approximately 50,000 each year. HIV-1 consists of four distinct groups: the major M group, and the rare N, O, and P groups, each comprising of various subtypes. Without proper care, HIV-1 can lead to cardiovascular, kidney, and liver diseases, cancer, and rapid progression into acquired immune deficiency syndrome (AIDS). Here, we describe a novel, rapid, and highly sensitive assay for the detection of HIV-1 using intercalating dye based RT-PCR and melt curve analysis. MATERIALS AND METHODS: We designed an RT-PCR assay for the detection of the major M subtypes in addition to the rare (O, N, and P) HIV-1 groups, as well as an extraction/RT-PCR control, using melt curve analysis. Viral RNA was extracted using the automated Qiagen EZ1 robotic system (Qiagen, Valencia, CA). To establish the limit of detection (LOD) for this assay, we diluted the AcroMetrix HIV-1 panel (LifeTechnologies, Grand Island, NY) to concentrations ranging from 25 to 500 copies/ml. Armored RNA BCR/ABL b3/a2 (Asuragen, Austin, Texas) was used as our extraction and RT-PCR control. Specificity and accuracy were assessed by testing plasma specimens from 48 anonymized patients negative for HIV-1. RESULTS: This assay has a turnaround time of less than 2.5h and has a limit of detection of 50 copies/ml of plasma. Our assay also demonstrated 100% concordance with 53 previously quantified plasma patient specimens, including 48 negative samples and 5 positive samples. HIV-1 and our extraction/RT-PCR control were consistently identified at 79 °C and 82.5 °C, respectively. CONCLUSIONS: We developed a comprehensive, easy to use assay for the detection of HIV-1 in human plasma. Our assay combines a rapid and cost-effective method for molecular diagnostics with the versatility necessary for widespread laboratory use. These performance characteristics make this HIV-1 detection assay highly suitable for use in a clinical laboratory.

Experimental demonstration of a reconfigurable silicon thermo-optical device based on spectral tuning of ring resonators for optical signal processing.

We have experimentally demonstrated a reconfigurable silicon thermo-optical device able to tailor its intrinsic spectral optical response by means of the thermo-optical control of individual and uncoupled resonant modes of micro-ring resonators. Preliminarily results show that the device's optical response can be tailored to build up distinct and reconfigurable logic levels for optical signal processing, as well as control of overall figures of merit, such as free-spectral-range, extinction ratio and 3 dB bandwidth. In addition, the micro-heaters on top of the ring resonators are able to tune the resonant wavelength with efficiency of 0.25 nm/mW within a range of up to 10 nm, as well as able to switch the resonant wavelength within fall and rise time of 15 µs.

Advantages of a combined rheumatoid arthritis magnetic resonance imaging score (RAMRIS) for hand and feet: does the RAMRIS of the hand alone underestimate disease activity and progression?

BACKGROUND: To evaluate a combined rheumatoid arthritis magnetic resonance imaging score (RAMRIS) for hand and foot (HaF-score) in rheumatoid arthritis (RA). METHODS: Magnetic resonance imaging (MRI, 0.2 Tesla) of the dominant hand and foot of 26 ACPA positive RA patients before and 6 months after initiation of methotrexate was obtained. RAMRIS of the hand was complemented by corresponding scoring of the foot (MTP I-V; HaF-score). Disease Activity Score 28 (DAS28) and a tender and swollen joint count (JC) of the joints scored in MRI were recorded. Changes in these scores (Δ) were assessed. RESULTS: ΔHaF-score correlated significantly with ΔDAS28 (r = 0.820, 95%-CI 0.633-0.916). Correlations to ΔDAS28 were best for changes in the synovitis subscore (0.648) and bone marrow edema (0.703). Correlations to ΔDAS28 were significantly better for of the ΔHaF-score than ΔRAMRIS (0.499, 0.139-0.743, p = 0.0368).All patients with at least moderate response (EULAR criteria, n = 11) had continuing disease activity on MRI, including five cases with new erosions, three of them at the feet. Improvements of the hand JC or foot JC were seen in 16 and 15 cases, respectively. However, MRI of the hand or feet improved in only 10 and 9 cases, respectively. No patient fulfilled SDAI remission criteria. CONCLUSIONS: The HaF-score identifies patients with continuing disease activity despite clinical response that would have been missed by consideration of the traditional RAMRIS or the DAS28 alone. Response as opposed to remission may be an insufficient goal in RA as all patients showed continuing disease activity, especially at the feet.

Democratizing molecular diagnostics for the developing world.

OBJECTIVES: Infectious diseases that are largely treatable continue to pose a tremendous burden on the developing world despite the availability of highly potent drugs. The high mortality and morbidity rates of these diseases are largely due to a lack of affordable diagnostics that are accessible to resource-limited areas and that can deliver high-quality results. In fact, modified molecular diagnostics for infectious diseases were rated as the top biotechnology to improve health in developing countries. METHODS: In this review, we describe the characteristics of accessible molecular diagnostic tools and discuss the challenges associated with implementing such tools at low infrastructure sites. RESULTS: We highlight our experience as part of the "Grand Challenge" project supported by the Gates Foundation for addressing global health inequities and describe issues and solutions associated with developing adequate technologies or molecular assays needed for broad access in the developing world. CONCLUSIONS: We believe that sharing this knowledge will facilitate the development of new molecular technologies that are extremely valuable for improving global health.

Ultrasensitive gas-phase chemical sensing based on functionalized photonic crystal nanobeam cavities.

Photonic crystal nanobeam cavities with high-quality factors are very sensitive to the changes of the dielectric properties of their surroundings. Utilizing this high sensitivity and by applying chemical functionalization, an ultrasensitive chemical sensor for gases based on a nanobeam cavity was demonstrated. A limit of detection of 1.5 parts-per-billion (ppb) in ambient conditions, determined from the noise level of the system, was achieved for nerve agent simulant methyl salicylate. The nanobeam cavity's nonlinear thermo-optical bistability is also utilized to realize a threshold detector for cumulative chemical exposure.

Diagnostic accuracy of ultrasound, ¹8F-FDG-PET/CT, and fused ¹8F-FDG-PET-MR images with DWI for the detection of cervical lymph node metastases of HNSCC.

OBJECTIVE: This study aimed to compare (18)F-fluorodesoxyglucose positron emission tomography/MRI ((18)F-FDG-PET-MRI) fusion images, including diffusion-weighted imaging (DWI), (18)F-FDG-PET/CT, and ultrasound (US) regarding their performance in nodal staging of patients with head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Eighteen patients prospectively underwent ultrasound examination, (18)F-FDG- PET/CT, and MRI before oral tumor resection and bilateral neck dissection. PET data sets were fused with contrast-enhanced T1-weighted MR images. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for nodal detection were calculated for all the imaging modalities. Furthermore, the accuracy of the correct N-staging was calculated for all methods. Detailed histopathology served as the standard of reference. RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy for detection of lymph node metastases were 63, 99, 86, 96, and 95 % for ultrasound; 30, 97, 56, 92, and 90 % for (18)F-FDG-PET/CT; 52, 96, 59, 94, and 91 % for (18)F-FDG-PET-MRI; and 53, 97, 67, 95, and 92 % for (18)F-FDG-PET-MRI plus DWI, respectively. There was no significant difference in the diagnostic accuracy for lymph node metastasis detection between (18)F-FDG-PET-MRI and (18)F-FDG-PET/CT (p = 0.839) and between (18)F-FDG-PET-MRI plus DWI and (18)F-FDG-PET/CT (p = 0.286), respectively. US was significantly more accurate than (18)F-FDG-PET/CT (p = 0.009), whereas no significant difference was seen between (18)F-FDG-PET-MRI and US (p = 0.223) or (18)F-FDG-PET-MRI plus DWI and US (p = 0.115). The nodal stage was correctly rated by (18)F-FDG-PET-MRI in eight patients, (18)F-FDG-PET-MRI plus DWI in nine patients, US in 12 patients, and (18)F-FDG-PET/CT in five out of 18 patients. CONCLUSION: Software-based fusion of (18)F-FDG-PET-MRI and (18)F-FDG-PET-MRI plus DWI may not increase nodal detection and N-staging performance in patients with oral malignancies compared to US and (18)F-FDG-PET/CT. CLINICAL RELEVANCE: Surgical staging of cervical lymph nodes will not be replaced even by advanced imaging modalities in the near future.

Hybrid single quantum well InP/Si nanobeam lasers for silicon photonics.

We report on a hybrid InP/Si photonic crystal nanobeam laser emitting at 1578 nm with a low threshold power of ~14.7 µW. Laser gain is provided from a single InAsP quantum well embedded in a 155 nm InP layer bonded on a standard silicon-on-insulator wafer. This miniaturized nanolaser, with an extremely small modal volume of 0.375(λ/n)(3), is a promising and efficient light source for silicon photonics.

Severe everolimus-induced steatohepatis: a case report.

The mammalian target of rapamycin inhibitors are normally favored as immunosuppressant agents for solid organ transplantation such as kidney, liver or heart. Only in recent years have they been increasingly administered for the treatment of neuroendocrine tumors. Even though mammalian target of rapamycin inhibitors are known to exhibit specific side effects, everolimus-related severe hepatic steatosis has not as yet been described in the literature. We report the case of a 76-year-old man who developed severe hepatic steatosis within four weeks of treatment with everolimus as concomitant tumor therapy for a progressively growing neuroendocrine carcinoma of the ileum. A diagnosis of hepatic steatosis was established using computer tomography and fibroscan©. Other underlying causes for steatosis hepatis could be excluded. Further studies are warranted to explain the underlying mechanisms.

Coincidence of active Crohn's disease and florid endometriosis in the terminal ileum: a case report.

Crohn's disease (CD), a variant of chronic inflammatory bowel disease, frequently affects the terminal ileum and coecal region. The clinical symptoms are often subtle and depend on the inflammatory activity of disease. In women of child-bearing age, florid intestinal endometriosis can simulate CD. Moreover, current pathophysiological concepts include intestinal endometriosis as a putative founder lesion for consecutive CD establishment. The report summarizes clinical and histomorphological data of a 35-year-old woman with the rare coincidence of florid intestinal endometriosis and CD both affecting the terminal ileum. The patient was suffering over 10 years from strong abdominal disorders including constipation, diarrhea, weight loss, and diffuse abdominal pain. In magnetic resonance imaging-Sellink, strong inflammation and intestinal obstruction of the terminal ileum were found. The laparoscopy revealed further evidence for existence of an inflammatory disease like CD, but brownish spots on the peritoneum were found indicative for endometriosis. Surgical resection of the terminal ileum and the coecal segment was performed followed by histopathological investigations. In transmural sections of the terminal ileum, histomorphological features of florid endometriosis intermingled with florid CD was found. The diagnostic findings were substantiated with a panel of immunohistological stainings. In conclusion, the findings demonstrate that florid endometriosis persists in florid CD lesions and the putative link between intestinal endometriosis and CD is more complex than previously assumed.

Supercolor coding methods for large-scale multiplexing of biochemical assays.

We present a novel method for the encoding and decoding of multiplexed biochemical assays. The method enables a theoretically unlimited number of independent targets to be detected and uniquely identified in any combination in the same sample. For example, the method offers easy access to 12-plex and larger PCR assays, as contrasted to the current 4-plex assays. This advancement would allow for large panels of tests to be run simultaneously in the same sample, saving reagents, time, consumables, and manual labor, while also avoiding the traditional loss of sensitivity due to sample aliquoting. Thus, the presented method is a major technological breakthrough with far-reaching impact on biotechnology, biomedical science, and clinical diagnostics. Herein, we present the mathematical theory behind the method as well as its experimental proof of principle using Taqman PCR on sequences specific to infectious diseases.

Self-aligned active quantum nanostructures in photonic crystals via selective wet-chemical etching.

We propose a method of forming quantum-size emitters within a pre-defined photonic crystal in a self-aligned fashion through controlled removal of quantum well layers via selective wet-chemical etching. To demonstrate the effectiveness of our method, we take the example of a two-dimensional photonic crystal slab containing multiple quantum wells at its center. We successfully fabricate vertically stacked quantum nanostructures (or quantum dots) well aligned with respect to the photonic crystal backbone. Micro-photoluminescence measurements performed at 78 K reveal that the radiative transition energy blue-shifts when the lateral dimension reaches less than 100 nm, which is compared with a simple model based on the 'particle-in-a-box' picture. The proposed method may find a broad range of applications in photonics and quantum optics, where the coupling between an emitter and an optical mode needs to be maximized.