Minimizing cross-axis sensitivity in grating-based optomechanical accelerometers.

Cross-axis sensitivity of single-axis optomechanical accelerometers, mainly caused by the asymmetric structural design, is an essential issue primarily for high performance applications, which has not been systematically researched. This paper investigates the generating mechanism and detrimental effects of the cross-axis sensitivity of a high resoluion single-axis optomechanical accelerometer, which is composed of a grating-based cavity and an acceleration sensing chip consisting of four crab-shaped cantilevers and a proof mass. The modified design has been proposed and a prototype setup has been built based on the model of cross-axis sensitivity in optomechanical accelerometers. The characterization of the cross-axis sensitivity of a specific optomechanical accelerometer is quantitatively discussed for both mechanical and optical components by numerical simulation and theoretical analysis in this work. The analysis indicates that the cross-axis sensitivity decreases the contrast ratio of the interference signal and the acceleration sensitivity, as well as giving rise to an additional optical path difference, which would impact the accuracy of the accelerometer. The improved mechanical design is achieved by double side etching on a specific double-substrate-layer silicon-on-insulator (SOI) wafer to move the center of the proof mass to the support plane. The experimental results demonstrate that the modified design with highly symmetrical structure can suppress the cross-axis sensitivity significantly without compromising the sensitivity and resolution. The cross-axis sensitivity defined by the contrast ratio of the output signal drops to 2.19% /0.1g from 28.28%/0.1g under the premise that the acceleration sensitivity of this single-axis optomechanical accelerometer remains 1162.45V/g and the resolution remains 1.325µg.

Highly sensitive lateral deformable optical MEMS displacement sensor: anomalous diffraction studied by rigorous coupled-wave analysis.

This paper discusses the pulse signal of a highly sensitive lateral deformable optical microelectromechanical systems (MEMS) displacement sensor based on Wood's anomalies and its corresponding tolerance. The optical reflection amplitude of the device changes with the displacement of the nanostructured grating elements. Unexpectedly, the device's original sinusoidal signal develops into a new signal form (i.e., a pulse signal), when the air gap between the two layers of gratings decreases. Since the slope of the pulse signal, namely 2.5%/nm (i.e., 0.65 dB/nm), is eight times higher than that of the original signal form, namely 0.3%/nm (i.e., 0.03 dB/nm), the sensitivity of the structure improves by eight times. However, this device is very sensitive to parameters such as its wavelength, period, duty ratio, and air gap. In this paper we used rigorous coupled wavelength analysis (RCWA) to analyze and optimize the respective influence of each parameter on the device's performance. We have introduced two methods to search for the optimal setting and have demonstrated the optimal settings of different incident lights. The simulation results indicate that it is close to 85% possible to achieve an actual device with the highest slope superior to 0.5%/nm and it is 64% possible that the highest slope of an actual device falls in the interval ranging from 1.0%/nm to 2.0%/nm. All the simulated data helped us better understand the tolerance of the pulse signal and guide us toward the development of an actual device.

Positive effects of an extracellular matrix hydrogel on rat anterior cruciate ligament fibroblast proliferation and collagen mRNA expression.

BACKGROUND/OBJECTIVE: We have previously shown that an extracellular matrix (ECM) bioscaffold derived from porcine small intestine submucosa (SIS) enhanced the healing of a gap injury of the medial collateral ligament as well as the central third defect of the patellar tendon. With the addition of a hydrogel form of SIS, we found that a transected goat anterior cruciate ligament (ACL) could also be healed. The result begs the research question of whether SIS hydrogel has positive effects on ACL fibroblasts (ACLFs) and thus facilitates ACL healing. METHODS: In the study, ECM-SIS hydrogel was fabricated from the digestion of decellularised and sterilised sheets of SIS derived from αGal-deficient (GalSafe) pigs. As a comparison, a pure collagen hydrogel was also fabricated from commercial collagen type I solution. The morphometrics of hydrogels was assessed with scanning electron microscopy. The ECM-SIS and collagen hydrogels had similar fibre diameters (0.105 ± 0.010 µm vs. 0.114 ± 0.004 µm), fibre orientation (0.51 ± 0.02 vs. 0.52 ± 0.02), and pore size (0.092 ± 0.012 µm vs. 0.087 ± 0.008 µm). The preservation of bioactive properties of SIS hydrogel was assessed by detecting bioactive molecules sensitive to processing and enzyme digestion, such as growth factors fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta 1 (TGF-ß1), with enzyme-linked immunosorbent assay. ACLFs were isolated and expanded in culture from explants of rat ACLs (n = 3). The cells were then seeded on the hydrogels and cultured with 0%, 1%, and 10% foetal bovine serum (FBS) for 3 days and 7 days. Cell attachment was observed using a light microscope and scanning electron microscopy, whereas cell proliferation and matrix production (collagen types I and III) were examined with bromodeoxyuridine assays and reverse transcription-polymerase chain reaction, respectively. RESULTS: The results showed that FGF-2 and TGF-ß1 in the SIS hydrogel were preserved by 50% (65.9 ± 26.1 ng/g dry SIS) and 90% (4.4 ± 0.6 ng/g dry SIS) relative to their contents in ECM-SIS sheets, respectively. At Day 3 of culture, ACLFs on the SIS hydrogel were found to proliferate 39%, 31%, and 22% more than those on the pure collagen hydrogel at 0%, 1%, and 10% FBS, respectively (p < 0.05). Collagen type I mRNA expression was increased by 150%, 207%, and 100%, respectively, compared to collagen hydrogel (p < 0.05), whereas collagen type III mRNA expression was increased by 123% and 132% at 0% and 1% FBS, respectively (all p < 0.05) but not at 10% FBS. By Day 7, collagen type I mRNA expression was still elevated by 137% and 100% compared to collagen hydrogel at 1% and 10% FBS, respectively (p < 0.05). Yet, collagen type III mRNA levels were not significantly different between the two groups at any FBS concentrations. CONCLUSION: Our data showed that the ECM-SIS hydrogel not only supported the growth of ACLFs, but also promoted their proliferation and matrix production relative to a pure collagen hydrogel. As such, ECM-SIS hydrogel has potential therapeutic value to facilitate ACL healing at the early stage after injury.

Focused laser lithographic system with sub-wavelength resolution based on vortex laser induced opacity of photochromic material.

A focused laser lithographic system combines with vortex laser induced opacity of photochromic layer to write patterns with linewidth below wavelength. A photochromic layer is formed by coating the mixture of metanil yellow and aqueous PVA solution on the photoresist layer. In our system, the center of a lithographic laser with a 405 nm wavelength coincides with the center of vortex laser with a 532 nm wavelength. When a photochromic layer is illuminated by both lasers simultaneously, the absorbance for the lithographic laser decreases at the hollow region of the vortex laser but increases at its annular region, so that a transparent aperture for the lithographic laser is created and its size could be tuned by changing the power of vortex laser; therefore, the linewidth of written patterns is variable. Experimentally, using a 20× lens (NA = 0.4), this system condenses the linewidth of written patterns from 6614 to 350 nm.

Metabonomic study of genkwa flos-induced hepatotoxicity and effect of herb-processing procedure on toxicity.

A urinary metabonomic approach based on ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS) was developed to study the metabolic disturbances caused by the administration of Genkwa Flos (GF) to rats. Potential biomarkers of GF-induced toxic effects were screened out and identified, and the underlying toxicological mechanism as well as the detoxification of vinegar-processing procedure on this herb was discussed. Urine samples were analyzed by the established UPLC-MS method. With the help of serum biochemistry and histopathology results, metabolic disturbances induced by the exposure to GF and the detoxification of processing procedure were confirmed. The differences in the metabolic profiles of healthy and treated rats were clearly discriminated with the principal component analysis of the chromatographic data. Eight significantly changed metabolites were identified and interpreted as biomarkers for the hepatotoxicity and detoxification of processing procedure. This study indicated that a UPLC-MS-based metabonomic analysis of urine samples could be considered as a promising tool to predict the hepatotoxicity induced by the GF and the detoxification of traditional vinegar-processing procedure on this herb.

Optical accelerometer based on grating interferometer with phase modulation technique.

In this paper, an optical accelerometer based on grating interferometer with phase modulation technique is proposed. This device architecture consists of a laser diode, a sensing chip and an optoelectronic processing circuit. The sensing chip is a sandwich structure, which is composed of a grating, a piezoelectric translator and a micromachined silicon structure consisting of a proof mass and four cantilevers. The detected signal is intensity-modulated with phase modulation technique and processed with a lock-in amplifier for demodulation. Experimental results show that this optical accelerometer has acceleration sensitivity of 619 V/g and high-resolution acceleration detection of 3 µg in the linear region.

Realization of autofocusing system for laser direct writing on non-planar surfaces.

This paper presents an autofocusing system for laser direct writing on non-planar surfaces, including focus error signal detection and focusing control. The focus error signal detection is based on modified confocal techniques, which features easy implementation, independence of the tilt angles of non-planar surfaces, and excellent suppression of common-mode noise or variable system factors. We also present a macro/micro dual-drive mechanism and its synchronous operation for focusing control on non-planar surfaces. Finally, a performance evaluation of the autofocusing system is presented. The uniform line width of 2.1 µm for a pattern on a convex spherical substrate with a curvature radius of 100 mm shows the autofocusing system performs well.

Nanometer-scale displacement sensor based on phase-sensitive diffraction grating.

In this paper, a nanometer-scale displacement sensor based on a phase-sensitive diffraction grating with interferometeric detection is described and experimentally demonstrated. The proposed displacement sensor consists of a coherent light source, a microstepping motor controller, an integrated grating, a mirror, and a differential circuit. Experimental results show that the displacement sensor has a sensitivity of about 6 mV/nm and a resolution of less than 1 nm. This displacement measurement is an attractive technology with high sensitivity, broad dynamic range, good reliability, and immunity to electromagnetic interference.

Compact optical correlator based on one phase-only spatial light modulator.

An optical correlator that utilizes one phase-only spatial light modulator (SLM) combined with a mirror is proposed and demonstrated. This system is compressed by displaying the input and filter pattern on different parts of the same SLM. The background noise is separated from the correlation signal by superimposing a high-frequency carrier with the filter pattern except in the zero-frequency regions, which will improve the signal-to-noise ratio in pattern recognition. Our architecture is compact and the cost is relatively low by utilizing only one SLM.

The effects of multiple freeze-thaw cycles on the biomechanical properties of the human bone-patellar tendon-bone allograft.

Soft tissue allografts, such as the bone-patellar tendon-bone (BPTB) graft, have been frequently used for anterior cruciate ligament (ACL) reconstruction. As allografts are subjected to freezing and thawing for multiple cycles, the objective of this study was to measure the changes of the biomechanical properties of the human BPTB allograft after 4 and 8 freeze-thaw cycles in comparison to a single freeze-thaw cycle. Three BPTB specimens were procured from 21 human donors and divided into three groups: 1, 4, or 8 freeze-thaw cycles. Each freeze-thaw cycle consisted of freezing at -20 ± 10°C for more than 6 h and thawing at 22 ± 3°C for at least 6 h. Tensile testing of the BPTB specimens consisted of loading between 50 N and 250 N for 100 cycles and then loading to failure. Cyclic loading revealed a similar amount of creep (∼0.5 mm) among the three freeze-thaw cycles groups (p = 0.38). The stiffness of the BPTB graft for the 1, 4, and 8 freeze-thaw cycle groups were 244 ± 42 N/mm, 235 ± 39 N/mm, and 231 ± 40 N/mm, respectively (p = 0.43). Similar findings were obtained for the ultimate load of the BPTB graft (p = 0.14) and the tangent modulus of the PT substance (p = 0.41). The results of this study suggest that there would be little measurable effect on the structural properties of the BPTB graft or mechanical properties of the PT tissue substance following 8 freeze-thaw cycles. These BPTB allografts could potentially be re-frozen without a loss in their biomechanical properties, given appropriate storage and care.

Alpha1,3-galactosyltransferase knockout does not alter the properties of porcine extracellular matrix bioscaffolds.

Extracellular matrix (ECM) bioscaffolds, such as porcine small intestine submucosa (SIS) and urinary bladder matrix (UBM), have been successfully used to improve soft tissue healing. Yet they contain plenty of galactose α1,3 galactose (αGal) epitopes, which cause rejection responses in pig organ transplantation to human. Recently, ECM bioscaffolds derived from genetically modified pigs that are αGal-deficient (αGal(-)) have become available. To ensure that the ECM bioscaffolds from these pigs can be used as alternatives, we examined their morphological, bioactive and biomechanical properties and compared them with those from the wild-type pigs (n=5 per group). Morphologically, the αGal(-) ECMs were found to be similar to the wild-type ECMs in gross observation and matrix appearance with hematoxylin and eosin staining. Growth factors commonly known to be present in ECM bioscaffolds, including FGF-2, TGF-ß1, VEGF, IGF-1 and PDGF-BB, also showed no significant differences in terms of quantity (p>0.05) and distribution in tissue from the results of enzyme-linked immunosorbent assay, Western blot analysis and immunohistochemistry. Furthermore, a bromodeoxyuridine cell proliferation assay confirmed the bioactivity of the extracts from the αGal(-) bioscaffolds to be similar to the wild-type bioscaffolds. Under uniaxial tensile testing, no significant differences were found between the αGal(-) and wild-type bioscaffolds in terms of their viscoelastic and mechanical properties (p>0.05). These multidisciplinary results suggest that genetic modification to eliminate the αGal epitopes in the ECM bioscaffolds had not altered the properties of these ECM bioscaffolds and, as such, they should retain their performance in tissue engineering in humans.

A metabonomic analysis of urine from rats treated with rhizoma alismatis using ultra-performance liquid chromatography/mass spectrometry.

A metabonomic approach based on ultra-performance liquid chromatography coupled to mass spectrometry (UPLC/MS) was used to study the nephrotoxicity of rhizoma alismatis (RA) in rats. Potential biomarkers of RA toxicity were identified and the toxicological mechanism is discussed. Urine samples were collected from control and treated rats at various stages and analyzed by UPLC/MS in positive ionization mode. Histopathological analysis was used to evaluate renal function. The differences in the metabolic profiles of the control and treated rats were clearly distinguishable with principal components analysis (PCA) of the chromatographic data, and significant changes in 13 metabolite biomarkers were detected in the urine. This metabonomic method combined with PCA could discriminate the treated rats from the control rats on days 60, 120, and 180 after treatment, before serious organic renal damage was apparent on day 180 with histopathology. This research indicates that UPLC/MS-based metabonomic analysis of urine samples can be used to predict the chronic nephrotoxicity induced by rhizoma alismatis.

A sensitive liquid chromatography-mass spectrometry method for simultaneous determination of alisol A and alisol A 24-acetate from Alisma orientale (Sam.) Juz. in rat plasma.

A liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for the simultaneous determination of alisol A and alisol A 24-acetate from Alisma orientale (Sam.) Juz. in rat plasma using diazepam as an internal standard. A 200-µl plasma sample was extracted by methyl tert-butyl ether and the separation was performed on Kromasil C(18) column (150 × 4.6 mm, 5 µm) with the mobile phase of acetonitrile (containing 0.1% of formic acid)-water (73:27, v/v) at a flow rate of 0.8 ml/min in a run time of 10 min. The two analytes were monitored with positive electrospray ionization by selected ion monitoring mode. The lower limit of quantitation for both alisol A and alisol A 24-acetate were 10 ng/ml. The calibration curves were linear in the measured range 10-1,000 ng/ml for alisol A and 10-500 ng/ml for alisol A 24-acetate. The mean extraction recoveries were above 74.7% for alisol A and above 72.4% for alisol A 24-acetate from biological matrixes. The intra- and inter-day precision for all concentrations of quality controls was lower than 14.1% (RSD %) for each analyte. The accuracy ranged from -12.3% to 9.8% (RE %) for alisol A, and -8.6% to 14.2% (RE %) for alisol A 24-acetate. The method was successfully applied to the study on the pharmacokinetics of alisol A and alisol A 24-acetate in rat plasma.

Laser direct writing using submicron-diameter fibers.

In this paper, a novel direct writing technique using submicron-diameter fibers is presented. The submicron-diameter fiber probe serves as a tightly confined point source and it adopts micro touch mode in the process of writing. The energy distribution of direct writing model is analyzed by Three-Dimension Finite-Difference Time-Domain method. Experiments demonstrate that submicron-diameter fiber direct writing has some advantages: simple process, 350-nm-resolution (lower than 442-nm-wavelength), large writing area, and controllable width of lines. In addition, by altering writing direction of lines, complex submicron patterns can be fabricated.

Positive changes in bone marrow-derived cells in response to culture on an aligned bioscaffold.

Previous studies have shown that cultured cells align with the local topography of their substrate following a concept called "contact guidance." Additionally, if the topography is highly aligned, the cells produce newly synthesized matrix that is also aligned. The objective of this study was to elucidate the positive effect of cell seeding on an elongated porcine small intestinal submucosa (SIS), which has been shown to improve ligament and tendon healing, by measuring the cellular response as a result of the changes in alignment. Because elongation is known to align the fibers of SIS through recruitment along the direction of elongation, we hypothesized that rabbit bone marrow-derived cells (BMDCs) seeded on SIS with improved fiber alignment would increase the expression and production of collagen following the concept of contact guidance. Using the small-angle light-scattering technique, it was found that a 15% elongation together with BMDC seeding on SIS (elongated, seeded group) improved its alignment of collagen fibers up to 16 times more than no elongation and no BMDC seeding (non-elongated, non-seeded group). Furthermore, BMDCs were also aligned along the direction of elongation and showed 200% greater collagen type I gene expression in the elongated, seeded group than in Petri dish controls. More importantly, the production of collagen was also 24% greater. The results of this study demonstrate that alignment of a bioscaffold can result in positive changes in cellular response, making the bioscaffold more attractive for functional tissue engineering to potentially enhance healing of ligaments and tendons.

Design of a panoramic annular lens with a long focal length.

A new method to improve the design of the panoramic annular lens (PAL) optical system with long focus is introduced. Cemented lenses are used in a PAL block to improve the design freedom. A multilayer diffractive optical element (MDOE) is used in relay optics to simplify the structure of the system and to increase diffractive efficiency of the design spectral range. The diffractive efficiency of MDOE in a wide spectral range is investigated theoretically. A seven piece PAL system with a total effective focal length of 10.8 mm is realized, and the diffractive efficiency of the whole design wavelength is above 99.3%. A PAL system with all spherical surfaces is described as a comparison.

Repetitive mechanical stretching modulates IL-1beta induced COX-2, MMP-1 expression, and PGE2 production in human patellar tendon fibroblasts.

While mechanical loading is known to be essential in maintaining tendon homeostasis, repetitive mechanical loading has also been implicated in the etiology of tendon overuse injuries. The purpose of this study was to determine whether cyclic mechanical stretching regulates inflammatory responses induced by interleukin-1beta (IL-1beta) treatment in human patellar tendon fibroblasts (HPTFs). HPTFs were grown in microgrooved silicone dishes, where they became elongated in shape and aligned with the microgrooves, which is similar to the shape and organization of tendon fibroblasts in vivo. Cyclic uniaxial stretching was then applied to silicone culture dishes with a 4% or 8% stretch at a stretching frequency of 0.5 Hz for a duration of 4 h in the presence or absence of 10 pM IL-1beta treatment. Non-stretched cells in the presence or absence of IL-1beta were used for controls, respectively. The expression of cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1), and the production of prostaglandin E2 (PGE2) were measured. In the absence of stretching, it was found that 10 pM of IL-1beta markedly induced higher levels of COX-2, MMP-1 gene expression, and PGE2 production than non-treated cells. Furthermore, cells with 4% stretching decreased the COX-2 and MMP-1 gene expression and PGE2 production that were stimulated by IL-1beta, whereas cells with 8% stretching further increased these gene products and/or expression levels in addition to the effects of IL-1beta stimulation. Thus, the results suggest that repetitive, small-magnitude stretching is anti-inflammatory, whereas large-magnitude stretching is pro-inflammatory. Therefore, moderate exercise may be beneficial to reducing tendon inflammation.

Controlling cell responses to cyclic mechanical stretching.

In most cell culture studies, cells are grown on smooth culture surfaces. Using microfabrication technology, we have developed microgrooved silicone surfaces to grow cells and subject them to repetitive mechanical stretching. When human patellar tendon fibroblasts were plated on these microgrooved surfaces, the cells had an elongated shape and underwent cyclic uniaxial stretching parallel to their long axes, all of which closely mimic conditions of tendon fibroblasts in vivo. Also, when fibroblasts were grown on microgrooves oriented at 45 and 90 degrees with respect to stretching direction, they did not change alignment or shape under cyclic mechanical stretching. Furthermore, compared to nonstretched cells, 8% cyclic stretching of tendon fibroblasts oriented at 0 (i.e., parallel to stretching direction), 45, and 90 degrees was found to increase alpha-SMA protein expression level by 46, 31, and 14%, respectively. In addition, 8% cyclic stretching tendon fibroblasts for 4 and 8 h oriented parallel to stretching direction increased alpha-SMA protein expression level by 25 and 57%, respectively. Thus, the results of this study showed that alpha-SMA protein expression levels of tendon fibroblasts depend on cell orientation with respect to stretching direction and stretching duration. We suggest that microgrooved silicone substrates can be used to study biological responses of tendon or ligament fibroblasts to repetitive mechanical stretching conditions in a more controlled manner.

Proliferation and collagen production of human patellar tendon fibroblasts in response to cyclic uniaxial stretching in serum-free conditions.

We studied the effect of cyclic mechanical stretching on the proliferation and collagen mRNA expression and protein production of human patellar tendon fibroblasts under serum-free conditions. The role of transforming growth factor-beta1 (TGF-beta1) in collagen production by cyclically stretched tendon fibroblasts was also investigated. The tendon fibroblasts were grown in microgrooved silicone dishes, where the cells were highly elongated and aligned with the microgrooves. Cyclic uniaxial stretching with constant frequency and duration (0.5 Hz, 4 h) but varying magnitude of stretch (no stretch, 4%, and 8%) was applied to the silicone dishes. Following the period of stretching, the cells were rested for 20 h in stretching-conditioned medium to allow for cell proliferation. In separate experiments, the cells were stretched for 4h and then rested for another 4 h. Samples of the medium, total cellular RNA and protein were used for analysis of collagen and TGF-beta1 gene expression and production. It was found that there was a slight increase in fibroblast proliferation at 4% and 8% stretch, compared to that of non-stretched fibroblasts, where at 8% stretch the increase was significant. It was also found that the gene expression and protein production of collagen type I and TGF-beta1 increased in a stretching-magnitude-dependent manner. And, levels of collagen type III were not changed, despite gene expression levels of the protein being slightly increased. Furthermore, the exogenous addition of anti-TGF-beta1 antibody eliminated the increase in collagen type I production under cyclic uniaxial stretching conditions. The results suggest that mechanical stretching can modulate proliferation of human tendon fibroblasts in the absence of serum and increase the cellular production of collagen type I, which is at least in part mediated by TGF-beta1.

Repetitively stretched tendon fibroblasts produce inflammatory mediators.

We studied the expression of cytosolic phospholipase-A2 and activity of secretory phospholipase-A2 by human patellar tendon fibroblasts subjected to cyclic mechanical stretching. The effect of different stretching frequencies on the production of prostaglandin-E2 and expression of cyclooxygenase enzyme were also examined. An in vitro system that can control alignment, shape, and mechanical loading conditions of tendon fibroblasts was used for this study. Cyclic stretching of fibroblasts increased the expression level of cytosolic phospholipase-A2 by 88% and activity level of secretory phospholipase-A2 by 190%, compared with those of nonstretched fibroblasts. Cyclic stretching of tendon fibroblasts at 0.1 Hz and 1.0 Hz also increased prostaglandin-E2 production by 40% and 69%, respectively. Furthermore, cyclooxygenase-1 and cyclooxygenase-2 expression levels were increased in a stretching frequency-dependent manner, but cyclooxygenase-2 expression was increased more than that of cyclooxygenase-1. Because cytosolic phospholipase-A2 and secretory phospholipase-A2 are involved in the production of prostaglandin-E2 and other inflammatory mediators, this study suggests that regulation of phospholipase-A2 expression level may be an alternative approach to control in vivo tendon inflammation. The results of this study also may explain in part why activities that involve repetitive motion and high frequency loading of tendons are more likely to result in tendon inflammation.