Sensitive Urine Immunoassay for Visualization of Lipoarabinomannan for Noninvasive Tuberculosis Diagnosis.

Lipoarabinomannan (LAM) is a prospective noninvasive biomarker for tuberculosis (TB) diagnosis. Here, we report a visual immunoassay of high sensitivity for detecting LAM in urine samples toward TB diagnosis. This method uses a DNA-linked immunosorbent of LAM, followed by a transduction cascade into amplified visual signals using quantum dots (QDs) and calcein reaction with Cu2+ and copper nanoparticles (Cu NPs). The limit of detection (LOD) for LAM in the urine reaches 2.5 fg/mL and 25 fg/mL using a fluorometer and length readouts on strips, respectively, demonstrating an ultrahigh sensitivity. The clinical validation of the proposed assay was performed with 147 HIV-negative clinical urine specimens. The results show the sensitivity of test is 94.1% (16/17) for confirmed TB (culture-positive) and 85% (51/60) for unconfirmed TB (clinical diagnosis without positive culture results), respectively, when the test cutoff value is 40 fg/mL for TB. Its specificity is 89.2% (25/28) in non-TB and nontuberculous mycobacterial patients. The area under the curve (AUC) was 0.86 when controls were non-TB and LTBI patients, while the AUC was 0.92 when controls were only non-TB patients. This highly sensitive visual immunoassay of LAM has shown potential for noninvasive diagnosis of TB using urine samples.

Substitution of Ethylammonium Halides Enabling Lead-Free Tin-Based Perovskite Solar Cells with Enhanced Efficiency and Stability.

Tin (Sn)-based perovskite solar cells (PSCs) have attracted extensive attention due to the irlow toxicity and excellent optoelectric properties. Nonetheless, the development of Sn-based PSCs is still hampered by poor film quality due to the fast crystallization and the oxidation from Sn2+ to Sn4+. In this work, we compare and employ three ethylammonium halides, EAX (X = Cl, Br, I) to explore their roles in Sn-based perovskites and solar cells. We find that crystallinity and crystallization orientation of perovskites are optimized with the regulation of EAI. EABr leads to reduced defect density and enhanced crystallinity but also the lowest absorption and the widest band gap owing to the substitution of Br-. Notably, perovskites with EACl exhibit the best crystallinity, lowest defect density, and excellent antioxidant capacity benefiting from the partial substitution of Cl-. Consequently, the EACl-modified device achieves a champion PCE of 12.50% with an improved Voc of 0.79 V. Meanwhile, an unencapsulated EACl device shows excellent shelf stability with negligible efficiency degradation after 5400 h of storage in a N2-filled glovebox, and the encapsulated device retains its initial efficiency after continuous light illumination at the maximum power point for 100 h in air.

Homogeneous two-dimensional visual and fluorescence analysis of circulating tumor cells in clinical samples via steric hindrance regulated enzymes recognition cleavage and elongation.

Oncology detection technology is significant for the early detection of tumors. The current study reports a new method that uses folate receptor (FR) as circulating tumor cells (CTCs) marker and only folate modified T30 as a probe. This method also uses dual-enzyme assisted amplification strategy for homogeneous fluorescence as well as two-dimensional visual (color and distance) detection of SMMC-7721 liver cancer cells from clinical blood samples. This work was based on the steric hindrance caused by binding between FR and folate to regulate cleavage of folate-T30 by exonuclease I (Exo I) and to inhibit subsequent polymerization and extension reaction of the cleavage product by terminal deoxynucleotidyl transferase (TdT). It explores the use of CdTe QDs to selectively identify Cu2+ and polyT-template Cu NPs as a bridge combined with inkjet printing technology to make test strips that can be read through distance changes. Under fluorometer mode, limit of detection as low as 1 cells/mL was achieved. The color and distance reading modes can identify cells with concentrations as low as 5 and 1 cells/mL, respectively. This CTCs detection approach of fluorescence mode was further validated by using 50 clinical samples of liver cancer patients (19 negative and 31 positive). The results were in good agreement with FR-polymerase chain reaction (FR-PCR) kits, radiologic and pathological techniques. In addition, the quantitative results of distance reading test strips of CTCs in 22 clinical samples (8 negative and 14 positive) were also in 100% agreement with the findings of clinical kits, computed tomography (CT) and pathological tests.

Homogeneous Visual and Fluorescence Detection of Circulating Tumor Cells in Clinical Samples via Selective Recognition Reaction and Enzyme-Free Amplification.

Here we report a simple all-nucleic-acid enzyme-free catalyzed hairpin assembly assisted amplification strategy with quantum dots (QDs) as the nanoscale signal reporter for homogeneous visual and fluorescent detection of A549 lung cancer cells from clinical blood samples. This work was based on the phenomenon that CdTe QDs can selectively recognize Ag+ and C-Ag+-C and by using mucin 1 as the circulating tumor cells (CTCs) marker and aptamer as the recognition probe. Under optimized conditions, the limits of detections as low as 0.15 fg/mL of mucin 1 and 3 cells/mL of A549 cells were achieved with fluorescence signals. A 1 fg/mL concentration of mucin 1 and 100 cells/mL of A549 can be distinguished by the naked eye. This method was used to quantitatively analyze CTCs in 51 clinical whole blood samples of patients with lung cancer. The levels of CTCs detected in clinical samples by this method were consistent with those obtained using the folate receptor-polymerase chain reaction clinical test kit and correlated with radiologic and pathological findings.

High-stability pH sensing with a few-layer MoS2 field-effect transistor.

Recently, molybdenum disulfide (MoS2), an emerging 2D material, has become an alternative candidate for ultra-sensitive biosensors due to its semiconducting behavior and the unique layer-by-layer atomic structure. Here, we report on highly stable and repeatable real-time pH sensing with few-layer MoS2 field-effect transistor (FET) biosensors, fabricated with both HfO2 and Al2O3/HfO2 gate dielectrics on top of MoS2 flakes exfoliated from natural crystals onto SiO2/Si samples. Both types of sensors demonstrate a highly linear, stable and repeatable response over a wide pH range with near-ideal pH sensitivity close to the theoretical limit of 59.6 mV pH-1. Ascribing from a different device operation regime in the pH sensing test-subthreshold regime for a sensor with an Al2O3/HfO2 dielectric and linear regime for a sensor with HfO2-a sensor with Al2O3/HfO2 shows significantly higher current sensitivity (∼105-fold) and relatively better linearity than a sensor with HfO2, while the latter shows relatively higher stability and higher repeatability. An Al2O3/HfO2-coated MoS2 FET reveals a high sensitivity or low detection limit of 0.01 pH.

Polystyrene-coated Interdigitated Microelectrode Array to Detect Free Chlorine towards IoT Applications.

We apply interdigitated microelectrode array (IDA) sensors for water quality monitoring. IDA sensors with an ion-sensitive coating show higher sensitivity of about 600 mV with the hypochlorite ion concentration increasing from 0 to 10 ppm more than the traditional sensing method. The response mechanism and selectivity have been studied. Several material components that affect the sensing process were explored. Coupling agents and plasticizer were introduced into the coating material to improve the coating material quality and its adhesion to the electrodes. The stability/repeatability and linearity have been significantly improved.

Room-Temperature Continuous-Wave Operation of Organometal Halide Perovskite Lasers.

Solution-processed organic-inorganic lead halide perovskites have recently emerged as promising gain media for tunable semiconductor lasers. However, optically pumped continuous-wave lasing at room temperature, a prerequisite for a laser diode, has not been realized so far. Here, we report lasing action in a surface-emitting distributed feedback methylammonium lead iodide (MAPbI3) perovskite laser on a silicon substrate at room temperature under continuous-wave optical pumping. This outstanding performance is achieved because of the ultralow lasing threshold of 13 W/cm2, which is enabled by thermal nanoimprint lithography that directly patterns perovskite into a high- Q cavity with large mode confinement, while at the same time, it improves perovskite's emission characteristics. Our results represent a major step toward electrically pumped lasing in organic and thin-film materials as well as the insertion of perovskite lasers into photonic integrated circuits for applications in optical computing, sensing, and on-chip quantum information.

Continuous-wave operation in directly patterned perovskite distributed feedback light source at room temperature.

We report a directly patterned perovskite distributed feedback (DFB) resonator and show narrow amplified spontaneous emission (ASE) at pump powers as low as 0.1 W/cm2 under continuous-wave (CW) optical pumping conditions at room temperature. Compared to the pristine thin film photoluminescence spectrum, a 16-fold reduction in emission linewidth in the MAPbI3 DFB cavity was observed. The direct nanostructuring of perovskites was achieved by thermal nanoimprint lithography. Our findings pave the way toward realizing CW pumped perovskite lasers at room temperature and energy-efficient perovskite light sources.

Nanoimprinted perovskite metasurface for enhanced photoluminescence.

Recently, solution-processed hybrid halide perovskite has emerged as promising materials for advanced optoelectronic devices such as photovoltaics, photodetectors, light emitting diodes and lasers. In the mean time, all-dielectric metasurfaces with high-index materials have attracted attention due to their low-loss and high-efficient optical resonances. Because of its tunable by composition band gap in the visible frequencies, organolead halide perovskite could serve as a powerful platform for realizing high-index, low-loss metasurfaces. However, direct patterning of perovskite by lithography-based technique is not feasible due to material instability under moisture. Here we report novel organolead halide perovskite metasurfaces created by the cost-effective thermal nanoimprint technology. The nanoimprinted perovskite metasurface showed improved surface morphology and enhanced optical absorption properties. Significantly enhanced optical emission with an eight-fold enhancement in photoluminescence (PL) intensity was observed under room temperature. Temperature-dependent PL of perovskite nanograting metasurface was also investigated. Based on our results, we believe that thermal nanoimprint is a simple and cost-effective technique to fabricate perovskite-based metasurfaces, which could have broad impact on optoelectronic and photonic applications.

Nanoimprinted Perovskite Nanograting Photodetector with Improved Efficiency.

Recently, organolead halide-based perovskites have emerged as promising materials for optoelectronic applications, particularly for photovoltaics, photodetectors, and lasing, with low cost and high performance. Meanwhile, nanoscale photodetectors have attracted tremendous attention toward realizing miniaturized optoelectronic systems, as they offer high sensitivity, ultrafast response, and the capability to detect beyond the diffraction limit. Here we report high-performance nanoscale-patterned perovskite photodetectors implemented by nanoimprint lithography (NIL). The spin-coated lead methylammonium triiodide perovskite shows improved crystallinity and optical properties after NIL. The nanoimprinted metal-semiconductor-metal photodetectors demonstrate significantly improved performance compared to the nonimprinted conventional thin-film devices. The effects of NIL pattern geometries on the optoelectronic characteristics were studied, and the nanograting pattern based photodetectors demonstrated the best performance, showing approximately 35 times improvement on responsivity and 7 times improvement on on/off ratio compared with the nonimprinted devices. The high performance of NIL-nanograting photodetectors likely results from high crystallinity and favored nanostructure morphology, which contribute to higher mobility, longer diffusion length, and better photon absorption. Our results have demonstrated that the NIL is a cost-effective method to fabricate high-performance perovskite nanoscale optoelectronic devices, which may be suitable for manufacturing of high-density perovskite nanophotodetector arrays and to provide integration with state-of-the-art electronic circuits.

Large Molecular Weight Polymer Solar Cells with Strong Chain Alignment Created by Nanoimprint Lithography.

In this work, strong chain alignment in large molecular weight polymer solar cells is for the first time demonstrated by nanoimprint lithography (NIL). The polymer crystallizations in nonimprinted thin films and imprinted nanogratings with different molecular weight poly(3-hexylthiophene-2,5-diyl) (P3HT) are compared. We first observe that the chain alignment is favored by medium molecular weight (Mn = 25 kDa) P3HT for nonimprinted thin films. However, NIL allows large molecular weight P3HT (>40 kDa) to organize more strongly, which has been desired for efficient charge transport but is difficult to achieve through any other technique. Consequently P3HT/[6,6]-penyl-C61-butyric-acid-methyl-ester (PCBM) solar cells with large molecular weight P3HT nanogratings show a high power conversion efficiency of 4.4%, which is among the best reported P3HT/PCBM photovoltaics devices.

Efficient low bandgap polymer solar cell with ordered heterojunction defined by nanoimprint lithography.

In this work, we demonstrate the feasibility of using nanoimprint lithography (NIL) to make efficient low bandgap polymer solar cells with well-ordered heterojunction. High quality low bandgap conjugated polymer poly[2,6-(4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) nanogratings are fabricated using this technique for the first time. The geometry effect of PCPDTBT nanostructures on the solar cell performance is investigated by making PCPDTBT/C70 solar cells with different feature sizes of PCPDTBT nanogratings. It is found that the power conversion efficiency (PCE) increases with increasing nanograting height, PCPDTBT/C70 junction area, and decreasing nanograting width. We also find that NIL makes PCPDTBT chains interact more strongly and form an improved structural ordering. Solar cells made on the highest aspect ratio PCPDTBT nanostructures are among the best reported devices using the same material with a PCE of 5.5%.

Effects of nanostructure geometry on nanoimprinted polymer photovoltaics.

We demonstrate the effects of nanostructure geometry on the nanoimprint induced poly(3-hexylthiophene-2,5-diyl) (P3HT) chain alignment and the performance of nanoimprinted photovoltaic devices. Out-of-plane and in-plane grazing incident X-ray diffraction techniques are employed to characterize the nanoimprint induced chain alignment in P3HT nanogratings with different widths, spacings and heights. We observe the dependence of the crystallite orientation on nanostructure geometry such that a larger width of P3HT nanogratings leads to more edge-on chain alignment while the increase in height gives more vertical alignment. Consequently, P3HT/[6,6]-phenyl-C61-butyric-acid-methyl-ester (PCBM) solar cells with the highest density and aspect ratio P3HT nanostructures show the highest power conversion efficiency among others, which is attributed to the efficient charge separation, transport and light absorption.

Applications of Semiconductor Fabrication Methods to Nanomedicine: A Review of Recent Inventions and Techniques.

We live in a world of convergence where scientific techniques from a variety of seemingly disparate fields are being applied cohesively to the study and solution of biomedical problems. For instance, the semiconductor processing field has been primarily developed to cater to the needs of the ever decreasing transistor size and cost while increasing functionality of electronic circuits. In recent years, pioneers in this field have equipped themselves with a powerful understanding of how the same techniques can be applied in the biomedical field to develop new and efficient systems for the diagnosis, analysis and treatment of various conditions in the human body. In this paper, we review the major inventions and experimental methods which have been developed for nano/micro fluidic channels, nanoparticles fabricated by top-down methods, and in-vivo nanoporous microcages for effective drug delivery. This paper focuses on the information contained in patents as well as the corresponding technical publications. The goal of the paper is to help emerging scientists understand and improvise over these inventions.

Silicon multi-nanochannel FETs to improve device uniformity/stability and femtomolar detection of insulin in serum.

Here we demonstrate the use of multiple Si nanochannel (NC) or nanograting (NG) instead of the conventional single nanochannel or nanowire design in biosensors. The NG devices can significantly reduce device-to-device variation, and improve device performance, e.g. higher current, higher ON/OFF ratio, smaller subthreshold slope, lower threshold voltage Vt in buffer solution. NG devices also result in higher sensor stability in buffer and diluted human serum. We believe such improvements are due to reduced discrete dopant fluctuation in the Si nanowires and biochemical noise in the solution because of the multiple-channel design. The improved devices allow us to sense pH linearly with 3-aminopropyltriethoxysilane coated devices, and to selectively detect insulin with limit of detection down to 10 fM in both buffer solution and diluted human serum without pre-purification.

Electrokinetic effects on detection time of nanowire biosensor.

We develop a multiphysics model to study the contribution of electrokinetics on the biomolecular detection process and provide a physical explanation of the two to three orders of magnitude difference in detection time between experimental results and theoretical predications at ultralow concentration. The electrokinetic effects, including electrophoretic force and electroosmotic flow, have been systematically studied under various sensor design and test conditions. In a typical single nanowire-based sensor, it is found that electrokinetic effects could result in a reduction of detection time over 90 times, compared with that induced by pure biomolecular diffusion. The detection time difference is further enhanced by increasing the applied gate voltage or the number of nanowires. It is proposed that accelerated biomolecular detection at ultralow concentration could be achieved by appropriate combinations of electrokinetic effects and nanowire sensor design.

Nanoimprinted polymer solar cell.

Among the various organic photovoltaic devices, the conjugated polymer/fullerene approach has drawn the most research interest. The performance of these types of solar cells is greatly determined by the nanoscale morphology of the two components (donor/acceptor) and the molecular orientation/crystallinity in the photoactive layer. A vertically bicontinuous and interdigitized heterojunction between donor and acceptor has been regarded as one of the ideal structures to enable both efficient charge separation and transport. Synergistic control of polymer orientation in the nanostructured heterojunction is also critical to improve the performance of polymer solar cells. Nanoimprint lithography has emerged as a new approach to simultaneously control both the heterojunction morphology and polymer chains in organic photovoltaics. Currently, in the area of nanoimprinted polymer solar cells, much progress has been achieved in the fabrication of nanostructured morphology, control of molecular orientation/crystallinity, deposition of acceptor materials, patterned electrodes, understanding of structure-property correlations, and device performance. This review article summarizes the recent studies on nanoimprinted polymer solar cells and discusses the outstanding challenges and opportunities for future work.

Room-temperature quantum confinement effects in transport properties of ultrathin Si nanowire field-effect transistors.

Quantum confinement of carriers has a substantial impact on nanoscale device operations. We present electrical transport analysis for lithographically fabricated sub-5 nm thick Si nanowire field-effect transistors and show that confinement-induced quantum oscillations prevail at 300 K. Our results discern the basis of recent observations of performance enhancement in ultrathin Si nanowire field-effect transistors and provide direct experimental evidence for theoretical predictions of enhanced carrier mobility in strongly confined nanowire devices.

Biofriendly bonding processes for nanoporous implantable SU-8 microcapsules for encapsulated cell therapy.

Mechanically robust, cell encapsulating microdevices fabricated using photolithographic methods can lead to more efficient immunoisolation in comparison to cell encapsulating hydrogels. There is a need to develop adhesive bonding methods which can seal such microdevices under physiologically friendly conditions. We report the bonding of SU-8 based substrates through (i) magnetic self assembly, (ii) using medical grade photocured adhesive and (iii) moisture and photochemical cured polymerization. Magnetic self-assembly, carried out in biofriendly aqueous buffers, provides weak bonding not suitable for long term applications. Moisture cured bonding of covalently modified SU-8 substrates, based on silanol condensation, resulted in weak and inconsistent bonding. Photocured bonding using a medical grade adhesive and of acrylate modified substrates provided stable bonding. Of the methods evaluated, photocured adhesion provided the strongest and most stable adhesion.

Catecholaminergic axonal varicosities appear to innervate growth hormone-releasing hormone-immunoreactive neurons in the human hypothalamus: the possible morphological substrate of the stress-suppressed growth.

CONTEXT: Stress is considered to be a major factor in the regulation of growth. Psychosocial dwarfism, characterized with short stature, delayed puberty, and depression, is typically preceded by psychological harassment or stressful environment. It has been observed that stress suppresses GH secretion, possibly via the attenuation of GHRH secretion. However, the exact mechanism of the impact of stress on growth has not been elucidated yet. OBJECTIVE: Our previous studies revealed intimate associations between neuropeptide Y (NPY)-immunoreactive (IR) axonal varicosities and GHRH-IR perikarya in the human hypothalamus. Because NPY is considered to be a stress molecule, NPY-GHRH juxtapositions may represent an important factor of stress-suppressed GHRH release. In addition to NPY, catecholamines are among the major markers of stress. Thus, in the present study, we examined the putative juxtapositions between the catecholaminergic tyrosine hydroxylase (TH)-/dopamine-ß-hydroxylase-/phenylethanolamine N-methyltransferase-IR and GHRH-IR neural elements in the human hypothalamus. To reveal these juxtapositions, double-label immunohistochemistry was used. RESULTS: Our findings revealed that the majority of the GHRH-IR perikarya formed intimate associations with TH-IR fiber varicosities. The majority of these juxtapositions were found in the infundibular nucleus/median eminence. CONCLUSIONS: The lack of phenylethanolamine N-methyltransferase-GHRH associations and the small number of dopamine-ß-hydroxylase-GHRH juxtapositions suggest that the vast majority of the observed TH-GHRH juxtapositions represent dopaminergic associations. The density of the abutting TH-IR fibers on the surface of the GHRH perikarya suggests that these juxtapositions may be functional synapses, and thus, in addition to NPY, catecholamines may regulate GHRH secretion via direct synaptic mechanisms.