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.

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.

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.

Experimental demonstration of a unidirectional reflectionless parity-time metamaterial at optical frequencies.

Invisibility by metamaterials is of great interest, where optical properties are manipulated in the real permittivity-permeability plane. However, the most effective approach to achieving invisibility in various military applications is to absorb the electromagnetic waves emitted from radar to minimize the corresponding reflection and scattering, such that no signal gets bounced back. Here, we show the experimental realization of chip-scale unidirectional reflectionless optical metamaterials near the spontaneous parity-time symmetry phase transition point where reflection from one side is significantly suppressed. This is enabled by engineering the corresponding optical properties of the designed parity-time metamaterial in the complex dielectric permittivity plane. Numerical simulations and experimental verification consistently exhibit asymmetric reflection with high contrast ratios around a wavelength of of 1,550 nm. The demonstrated unidirectional phenomenon at the corresponding parity-time exceptional point on-a-chip confirms the feasibility of creating complicated on-chip parity-time metamaterials and optical devices based on their properties.

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.

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.

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.

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.

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.

Compact and low power consumption tunable photonic crystal nanobeam cavity.

A proof-of-concept for a new and entirely CMOS compatible tunable nanobeam cavity is demonstrated in this paper. Preliminary results show that a compact nanobeam cavity (~20 µm(2)) with high Q-factor (~50,000) and integrated with a micro-heater atop, is able of tuning the resonant wavelength up to 15 nm with low power consumption (0.35nm/mW), and of attaining high modulation depth with only ~100 µW. Additionally, a tunable bi-stable behavior is reported.

Higher-order defect-mode laser in an optically thick photonic crystal slab.

The use of an optically thick slab may provide versatile solutions for the realization of a current injection-type laser using photonic crystals. Here, we show that a transversely higher-order defect mode can be designed to be confined by a photonic bandgap in such a thick slab. Using simulations, we show that a high Q of >10(5) is possible from a finely tuned second-order hexapole mode (2h). Experimentally, we achieve optically pumped pulsed lasing at 1347 nm from the 2h with a peak threshold pump power of 88 µW.

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.

Low-field MRI versus ultrasound: which is more sensitive in detecting inflammation and bone damage in MCP and MTP joints in mild or moderate rheumatoid arthritis?

OBJECTIVES: The aim of the present paper is to determine if the ultrasound of hands and feet is comparable to the MRI of the dominant hand to detect erosive disease and inflammation in mild or moderate rheumatoid arthritis (RA). METHODS: Twenty-six patients (14 females; mean age, 48 years) with active mild or moderate RA (mean DAS28, 3.9; mean disease duration, 19 months) were examined clinically, by ultrasound and by gadolinium-enhanced low-field MRI at baseline, after 6 and 12 months (78 examinations). Radiographs from hands and forefeet were taken at baseline and after 12 months. MRI was performed at the clinically most active (dominant) hand or forefoot evaluating the MCP 1-5 or MTP 1-5 joints. Ultrasound examination additionally included all other 2nd, 5th MCP and 5th MTP joints. RESULTS: MRI and ultrasound detected erosive disease in 67 and 56 of 78 examinations, respectively (p<0.01); radiography only in 8 of 52 examinations (p<0.001). MRI and ultrasound were equally sensitive to detect synovitis (in 64 and 66 examinations). Synovial power Doppler signals were present in 38 ultrasound examinations. Bone marrow oedema was present in 37 MRI examinations. Ultrasound was more sensitive than MRI to detect tenosynovitis (in 30 vs. 15 examinations; p=0.001). CONCLUSIONS: MRI of the dominant hand and bilateral ultrasound of MCP and MTP joints are superior to x-ray to detect erosive disease in mild and moderate RA. MRI is slightly, but significantly more sensitive than ultrasound for erosive disease, while ultrasound is more sensitive to detect tenosynovitis. Ultrasound and MRI are comparably sensitive to detect synovitis.

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.

Molecular imaging of cartilage damage of finger joints in early rheumatoid arthritis with delayed gadolinium-enhanced magnetic resonance imaging.

OBJECTIVE: To assess cartilage glycosaminoglycan content and cartilage thickness in the metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis (RA) and healthy volunteers. METHODS: After review board approval and informed consent were obtained, 22 subjects were prospectively enrolled (9 patients with early RA [7 women and 2 men with a mean ± SD age of 49 ± 13 years; range 25-68 years] and 13 healthy volunteers [10 women and 3 men with a mean ± SD age of 51 ± 12 years; range 25-66 years). In a total of 44 MCP joints of the index and middle fingers, measurements of cartilage thickness and delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index (T1 [msec]) were obtained using the variable flip-angle method and a 3T MR scanner. MRIs were evaluated for bone edema, erosions, and synovitis (using the RA MRI Scoring criteria). Student's t-test was used to test the significance of differences between groups. RESULTS: The mean ± SD dGEMRIC index was 497 ± 86 msec in healthy volunteers and was significantly lower in the early RA group (421 ± 76 msec) (P = 0.042). There was no joint space narrowing seen on standard radiographs. No significant difference was found between cartilage thickness in patients with early RA and that in controls (index finger mean ± SD 1.27 ± 0.23 mm in RA patients versus 1.46 ± 0.34 mm in controls [P = 0.16] and middle finger 1.26 ± 0.23 mm in RA patients versus 0.97 ± 0.47 mm in controls [P = 0.10]). No significant correlation was noted between cartilage thickness and dGEMRIC index (R = 0.36, P = 0.88 in RA patients; R = 0.156, P = 0.445 in controls). CONCLUSION: Our findings indicate that cartilage damage is present in the MCP joints of patients with early RA despite the absence of joint space narrowing on standard radiographs and MRI. Cartilage damage in RA can be imaged with dGEMRIC.

Patterns of magnetic resonance imaging of the foot in rheumatoid arthritis: which joints are most frequently involved?

To investigate patterns of inflammatory MRI pathologies of the fore- and midfoot in rheumatoid arthritis (RA) and early RA (ERA) and their changes under therapy. In this prospective study, MRI data of the foot of 39 RA patients (29 female, 10 male; age: 54 ± 13 years; disease duration: 35 ± 37 months; baseline DAS28: 3.0 ± 2.0; medication: 29 DMARD, 1 biological, 9 symptomatic or non-specific treatment) were evaluated for synovitis in 314 joints, bone marrow edema and erosions according to RAMRIS criteria in a total of 585 joints. The change in joint pathology intensity was evaluated on follow-up MRI (time of follow-up: 8 ± 4 months) in 25 patients. Inflammation was generally more frequent in the metatarsophalangeal (MTP) joints (221/292; 76 %) than in the proximal metatarsal (47/292; 16 %) and tarsal bones (24/292; 8 %). The overall most frequently involved joints of the foot were MTP 5 (51/292; 18 %) and 1 (49/292; 17 %). Change under therapy was most frequently seen in the MTP 1 joint. Progress of inflammation in the MTP 1 was more frequently found in ERA patients than in patients with established RA (disease duration >12 months) (p = 0.002). In RA, the MTP joints, primarily MTP 5 and 1, are the predominant sites of inflammatory MRI pathologies of the foot. A change of inflammatory activity under therapy can be most frequently noted in the MTP 1 joint. This information might be helpful to improve effectiveness of MRI-controlled therapy approaches and clinical trials.

Pertinent reportable incidental cardiac findings on chest CT without electrocardiography gating: review of 268 consecutive cases.

BACKGROUND: Pertinent reportable cardiac findings on non-electrocardiography (ECG)-gated chest CT examinations have become easier to detect given recent advancements in multidetector CT technology. However, those findings are easily overlooked on routine chest CT without ECG gating given residual inherent cardiac motion artifact and non-cardiac indications. PURPOSE: To describe and quantify the types of pertinent reportable cardiac findings that can be detected on chest CT examinations without ECG gating and evaluate how often they were reported. MATERIAL AND METHODS: Two radiologists retrospectively reviewed (blinded to the original interpretation) 268 consecutive routine adult chest CT examinations without ECG gating for the presence of pertinent reportable cardiac findings. Retrospective interpretations were then compared with the original radiological reports. RESULTS: One hundred and sixty-three patients (61%) had pertinent reportable cardiac findings. The findings encountered included: coronary artery disease (n = 131; 80.0%), coronary artery bypass grafts (n = 10; 6.1%), left ventricular aneurysm (n = 1; 0.6%), valve calcification (n = 131; 80.0%), valve repair/replacement (n = 5; 3.1%), pericardial effusion (n = 33; 20.2%), left atrial appendage thrombus (n = 1; 0.6%), cardiac mass (n = 1; 0.6%), and cardiac chamber enlargement (n = 29; 17.8%). On the original radiological reports 22.3% of the pertinent reportable cardiac findings, detected by the two radiologists retrospectively, were not reported. CONCLUSION: Detection of pertinent reportable cardiac findings on routine chest CT examinations without ECG gating is possible. The high volume of chest CT examinations without ECG gating represents an opportunity for radiologists to comment on the presence or absence of cardiac disease which may influence future clinical decisions.

Reconfigurable silicon thermo-optical ring resonator switch based on Vernier effect control.

A proof-of-concept for a new and entirely CMOS compatible thermo-optic reconfigurable switch based on a coupled ring resonator structure is experimentally demonstrated in this paper. Preliminary results show that a single optical device is capable of combining several functionalities, such as tunable filtering, non-blocking switching and reconfigurability, in a single device with compact footprint (~50 µm x 30 µm).