Search

Abstract The ability to weigh microsubstances present in low concentrations is an important tool for environmental monitoring and chemical analysis. For instance, developing a rapid analysis platform that identifies the material type of microplastics in seawater would help evaluate the potential toxicity to marine organisms. In this study, we demonstrate the integration of two different techniques that bring together the functions of sparse particle localization and miniaturized mass sensing on a microelectromechanical system (MEMS) chip for enhanced detection and minimization of negative measurements. The droplet sample for analysis is loaded onto the MEMS chip containing a resonant mass sensor. Through the coupling of a surface acoustic wave (SAW) from a SAW transducer into the chip, the initially dispersed microparticles in the droplet are localized over the detection area of the MEMS sensor, which is only 200 µm wide. The accreted mass of the particles is then calibrated against the resulting shift in resonant frequency of the sensor. The SAW device and MEMS chip are detachable after use, allowing the reuse of the SAW device part of the setup instead of the disposal of both parts. Our platform maintains the strengths of noncontact and label-free dual-chip acoustofluidic devices, demonstrating for the first time an integrated microparticle manipulation and real-time mass measurement platform useful for the analysis of sparse microsubstances.

A technique and electronic circuit for contactless electromagnetic interrogation of piezoelectric micro-electromechanical system (MEMS) resonator sensors are proposed. The adopted resonator is an aluminum-nitride (AlN) thin-film piezoelectric-on-silicon (TPoS) disk vibrating in radial contour mode at about 6.3 MHz. The MEMS resonator is operated in one-port configuration and it is connected to a spiral coil, forming the sensor unit. A proximate electronic interrogation unit is electromagnetically coupled through a readout coil to the sensor unit. The proposed technique exploits interleaved excitation and detection phases of the MEMS resonator. A tailored electronic circuit manages the periodic switching between the excitation phase, where it generates the excitation signal driving the readout coil, and the detection phase, where it senses the transient decaying response of the resonator by measuring through a high-impedance amplifier the voltage induced back across the readout coil. This approach advantageously ensures that the readout frequency of the MEMS resonator is first order independent of the interrogation distance between the readout and sensor coils. The reported experimental results show successful contactless readout of the MEMS resonator independently from the interrogation distance over a range of 12 mm, and the application as a resonant sensor for ambient temperature and as a resonant acoustic-load sensor to detect and track the deposition and evaporation processes of water microdroplets on the MEMS resonator surface.

RET (REarranged during Transfection) is a receptor tyrosine kinase, which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activation of RET is a mechanism of oncogenesis in medullary thyroid carcinomas where both germline and sporadic activating somatic mutations are prevalent. At present, there are no known specific RET inhibitors in clinical development, although many potent inhibitors of RET have been opportunistically identified through selectivity profiling of compounds initially designed to target other tyrosine kinases. Vandetanib and cabozantinib, both multi-kinase inhibitors with RET activity, are approved for use in medullary thyroid carcinoma, but additional pharmacological activities, most notably inhibition of vascular endothelial growth factor - VEGFR2 (KDR), lead to dose-limiting toxicity. The recent identification of RET fusions present in ~1% of lung adenocarcinoma patients has renewed interest in the identification and development of more selective RET inhibitors lacking the toxicities associated with the current treatments. In an earlier publication [Newton et al, 2016; 1] we reported the discovery of a series of 2-substituted phenol quinazolines as potent and selective RET kinase inhibitors. Here we describe the development of the robust screening cascade which allowed the identification and advancement of this chemical series. Furthermore we have profiled a panel of RET-active clinical compounds both to validate the cascade and to confirm that none display a RET-selective target profile.

RET (REarranged during Transfection) is a receptor tyrosine kinase, which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activation of RET is a mechanism of oncogenesis in medullary thyroid carcinomas where both germline and sporadic activating somatic mutations are prevalent. At present, there are no known specific RET inhibitors in clinical development, although many potent inhibitors of RET have been opportunistically identified through selectivity profiling of compounds initially designed to target other tyrosine kinases. Vandetanib and cabozantinib, both multi-kinase inhibitors with RET activity, are approved for use in medullary thyroid carcinoma, but additional pharmacological activities, most notably inhibition of vascular endothelial growth factor - VEGFR2 (KDR), lead to dose-limiting toxicity. The recent identification of RET fusions present in ~1% of lung adenocarcinoma patients has renewed interest in the identification and development of more selective RET inhibitors lacking the toxicities associated with the current treatments. In an earlier publication [Newton et al, 2016; 1] we reported the discovery of a series of 2-substituted phenol quinazolines as potent and selective RET kinase inhibitors. Here we describe the development of the robust screening cascade which allowed the identification and advancement of this chemical series. Furthermore we have profiled a panel of RET-active clinical compounds both to validate the cascade and to confirm that none display a RET-selective target profile.

We present a 5.41 MHz square-extensional (SE) mode resonator in closed-loop oscillation for resonant mass sensing in the liquid phase. The resonator has been fabricated in piezoelectric thin film aluminum nitride (AlN) on silicon (Si). The strain profile of the SE mode allows for higher electromechanical coupling efficiency using piezoelectric transduction to lower the motional resistance (Rm) given the expected low quality factors (Q) in liquid (136 compared to 942 in air). By locking the device into self-sustained oscillation, the minimum detectable frequency shift is reduced from 3680 ppm (open-loop in water) to 8.76 ppm (closed-loop in air).

RET (REarranged during Transfection) is a receptor tyrosine kinase, which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activation of RET is a mechanism of oncogenesis in medullary thyroid carcinomas where both germline and sporadic activating somatic mutations are prevalent. At present, there are no known specific RET inhibitors in clinical development, although many potent inhibitors of RET have been opportunistically identified through selectivity profiling of compounds initially designed to target other tyrosine kinases. Vandetanib and cabozantinib, both multi-kinase inhibitors with RET activity, are approved for use in medullary thyroid carcinoma, but additional pharmacological activities, most notably inhibition of vascular endothelial growth factor - VEGFR2 (KDR), lead to dose-limiting toxicity. The recent identification of RET fusions present in ~1% of lung adenocarcinoma patients has renewed interest in the identification and development of more selective RET inhibitors lacking the toxicities associated with the current treatments. In an earlier publication [Newton et al, 2016; 1] we reported the discovery of a series of 2-substituted phenol quinazolines as potent and selective RET kinase inhibitors. Here we describe the development of the robust screening cascade which allowed the identification and advancement of this chemical series. Furthermore we have profiled a panel of RET-active clinical compounds both to validate the cascade and to confirm that none display a RET-selective target profile.

Cervical cancer is the second most common cancer in women worldwide. Human papillomavirus (HPV) is considered as the main cause of invasive cervical cancer and cervical intra-epithelial neoplasia. High risk HPV DNA has been shown to be present in 99.7% of cervical cancers. So HPV DNA testing for screening of cervical cancers may play a potential role in early detection and management of cervical cancer. With above background a cross sectional study was undertaken to estimate the prevalence and to identify the associated risk factors of human Papillomavirus infection among Visual Inspection with Acetic acid (VIA) positive women attending at colposcopy clinic of Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh from July 2013 to December 2014. One hundred and forty three cervical swabs for nested PCR were collected from the patients attending colposcopy clinic of MMCH, for detecting target gene of L1 region of the HPV genome. Among the 143 VIA positive patient nested PCR showed 49.6% (71/143) positive. Biopsy of 54 colposcopy positive women revealed that 16 (29.6%) cases were chronic cervicitis, 33 (61.1%) cases were mild dysplasia (C1NI), 01 (1.9%) were having moderate dysplasia (C1NII) and 04(7.4%) patients were diagnosed as invasive squamous cell carcinoma. So, high grade cervical lesions were 100% positive by nested PCR for HPV.