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Inflammation is a good thing when it's fighting off infection, but too much can lead to autoimmune diseases or cancer. In efforts to dampen inflammation, scientists have long been interested in CC chemokine receptor 2 (CCR2)—a protein that sits on the surface of immune cells like an antenna, sensing and transmitting inflammatory signals that spur cell movement toward sites of inflammation. Researchers at the Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego have now determined the 3D structure of CCR2 simultaneously bound to two inhibitors. Understanding how these molecules fit together may better enable pharmaceutical companies to develop anti-inflammatory drugs that bind and inhibit CCR2 in a similar manner.CCR2 and associated signaling molecules are known to play roles in a number of inflammatory and neurodegenerative diseases, including multiple sclerosis, asthma, diabetic nephropathy and cancer. Many drug companies have attempted to develop drugs that target CCR2, but none have yet made it to market."So far drugs that target CCR2 have consistently failed in clinical trials," said Tracy Handel, PhD, professor in the Skaggs School of Pharmacy. "One of the biggest challenges is that, to work therapeutically, CCR2 needs to be turned 'off' and stay off completely, all of the time. We can't afford ups and downs in its activity. To be effective, any small molecule drug that inhibits CCR2 would have to bind the receptor tightly and stay there. And that's difficult to do."Handel led the study with Irina Kufareva, PhD, project scientist at Skaggs School of Pharmacy, and Laura Heitman, PhD, of Leiden University. The study's first author is Yi Zheng, PhD, postdoctoral researcher also at Skaggs School of Pharmacy.CCR2 spans the membrane of immune cells. Part of the receptor sticks outside the cell and part sticks inside. Inflammatory molecules called chemokines bind the external part of CCR2 and the receptor carries that signal to the inside of the cell. Inside the cell, CCR2 changes shape and binds other communication molecules, such as G proteins, triggering a cascade of activity. As a result, the immune cells move, following chemokine trails that lead them to places in the body where help is needed.In this study, the researchers used a technique known as X-ray crystallography to determine the 3D structure of CCR2 with two molecules bound to it simultaneously—one at each end.That's a huge accomplishment because, Kufareva said, "Receptors that cross the cell membrane are notoriously hard to crystalize. To promote crystallization, we needed to alter the amino acid sequence of CCR2 to make the receptor molecules assemble in an orderly fashion. Otherwise, when taken out of the cell membrane, they tend to randomly clump together. "Handel, Kufareva and team also discovered that the two small molecules binding CCR2 turn the receptor "off" by different but mutually reinforcing mechanisms. One of the small molecules binds the outside face of the receptor and blocks binding of the natural chemokines that normally turn the receptor "on." The other small molecule binds the face of the receptor inside the cell, where the G protein normally binds, preventing inflammatory signal transmission. According to Handel, the latter binding site has never been seen before.   

At last week's IEEE International Electron Devices Meeting (IEDM) in San Francisco (USA), imec, the world-leading research and innovation hub in nano-electronics and digital technology and Holst Centre debuted a miniaturized sensor that simultaneously determines pH and chloride (Cl-)levels in fluid. This innovation is a must have for accurate long-term measurement of ion concentrations in applications such as environmental monitoring, precision agriculture and diagnostics for personalized healthcare. The sensor is an industry first and thanks to the SoC (system on chip) integration it enables massive and cost-effective deployments in Internet-of-Things (IoT) settings. Its innovative electrode design results in a similar or better performance compared to today's standard equipment for measuring single ion concentrations and allows for additional ion tests.Sensors based on ion-selective membranes are considered the gold standard to measure ion concentrations in many applications, such as water quality, agriculture, and analytical chemistry. They consist of two electrodes, the ion-sensitive electrode with the membrane (ISE) and a reference electrode (RE). When these electrodes are immersed in a fluid, a potential is generated that scales with the logarithm of the ion activity in the fluid, forming a measure for the concentration. However, the precision of the sensor depends on the long-term stability of the miniaturized RE, a challenge that has now been overcome."The common issue with such designs is the leaching of ions from the internal electrolyte, causing the sensor to drift over time," stated Marcel Zevenbergen, senior researcher at imec/Holst Centre. "To suppress such leaching, we designed and fabricated an RE with a microfluidic channel as junction and combined it with solid-state iridium oxide (IrOx) and silver chloride (AgCl) electrodes fabricated on a silicon substrate, respectively as indicating electrodes for pH and Cl-. Our tests demonstrated this to be a long-term stable solution with the sensor showing a sensitivity, accuracy and response time that are equal or better than existing solutions, while at the same time being much smaller and potentially less expensive.""We are providing groundbreaking sensing and analytics solutions for the IoT," stated John Baekelmans, Managing Director of imec in The Netherlands. "This new multi-ion sensor is one in a series that Holst Centre is currently developing with its partners to form the senses of the IoT. For each sensor, the aim is to leapfrog the current performance of the state-of-the-art sensors in a mass-producible, wireless, energy optimized and miniaturized package."Reference:ADXRS620BBGZLPY410ALTRL3GD20HTR  

An ISA100 Wireless-based field wireless vibration sensor from Yokogawa has the ability to quickly update data as well as a long battery life. ISA100 Wireless is a technology that is based on the ISA100.11a standard. It includes ISA100.11a-2011 communications, an application layer with process control industry standard objects, device descriptions and capabilities, a gateway interface, infrared provisioning, and a backbone router.By providing real-time updates on vibration levels in plant facilities, the new sensor helps users quickly detect equipment anomalies and enables predictive maintenance.With a field wireless system, plant field devices and analysers are able to communicate wirelessly with host-level monitoring and control systems.The rising need to improve productivity and enhance safety by collecting more data on plant operations is driving the demand for field wireless devices, which can be installed even in difficult to access locations.Field wireless devices have the added advantage of reducing installation costs.Vibration sensors are useful for the condition monitoring and predictive maintenance of plant machinery such as compressors, pumps, and motors.Conventional methods for monitoring vibration include the use of vibration sensors that rely on wired communications with a host system, and patrols by maintenance staff to collect vibration data.With the widening use of field wireless systems and the need to reduce installation costs, there is an increasing demand for wireless vibration sensors.Since releasing the world’s first ISA100 Wireless-based field wireless devices and wireless systems, Yokogawa has expanded its lineup of field wireless devices that measure temperature, pressure, flow rate, and the like.This new vibration sensor will meet the company’s customers’ needs for a device that can provide the quick updates on vibration levels needed to detect anomalies at an early stage.The principal components of this field wireless vibration sensor are the FN510 field wireless multifunction module, the LN01 piezoelectric type acceleration sensor, and the FN110 field wireless communication module.Via a gateway device, the FN510 uses the ISA100 Wireless communications protocol to exchange data with a host-level system such as a DCS. The data collected with this vibration sensor enables plant operators and maintenance staff to monitor vibration levels in real time. Both explosion-proof and non-explosion-proof types are available.Reference:D7E-1BU-27135-0001005447-1   

Researchers have proposed a design for the first DNA sequencer based on an electronic nanosensor that can detect tiny motions as small as a single atom. The proposed device—a type of capacitor, which stores electric charge—is a tiny ribbon of molybdenum disulfide suspended over a metal electrode and immersed in water. The ribbon is 15.5 nanometers (nm, billionths of a meter) long and 4.5 nm wide. Single-stranded DNA, containing a chain of bases (bits of genetic code), is threaded through a hole 2.5 nm wide in the thin ribbon. The ribbon flexes only when a DNA base pairs up with and then separates from a complementary base affixed to the hole. The membrane motion is detected as an electrical signal. As described in a new paper, the NIST team made numerical simulations and theoretical estimates to show the membrane would be 79 to 86 percent accurate in identifying DNA bases in a single measurement at speeds up to about 70 million bases per second. Integrated circuits would detect and measure electrical signals and identify bases. The results suggest such a device could be a fast, accurate and cost-effective DNA sequencer, according to the paper. Conventional sequencing, developed in the 1970s, involves separating, copying, labeling and reassembling pieces of DNA to read the genetic information. Newer methods include automated sequencing of many DNA fragments at once—still costly—and novel "nanopore sequencing" concepts. For example, the same NIST group recently demonstrated the idea of sequencing DNA by passing it through a graphene nanopore, and measuring how graphene's electronic properties respond to strain. The latest NIST proposal relies on a thin film of molybdenum disulfide—a stable, layered material that conducts electricity and is often used as a lubricant. Among other advantages, this material does not stick to DNA, which can be a problem with graphene. The NIST team suggests the method might even work without a nanopore—a simpler design—by passing DNA across the edge of the membrane. "This approach potentially solves the issue with DNA sticking to graphene if inserted improperly, because this approach does not use graphene, period," NIST theorist and lead author Alex Smolyanitsky said. "Another major difference is that instead of relying on the properties of graphene or any particular material used, we read motions electrically in an easier way by forming a capacitor. This makes any electrically conductive membrane suitable for the application." Nanomaterials expert Boris Yakobson of Rice University, a co-author on the paper, suggested the capacitor idea. Computational support was provided by the University of Groningen in the Netherlands. DNA has four bases. For the simulations, cytosine (C), which naturally pairs up with guanine (G), is attached to the inside of the pore. When a piece of DNA passes through the pore, any G in the strand temporarily attaches to the embedded C, pulling on the nanoribbon and signaling the electrode. The DNA sequence is determined by measuring how and when electrical blips vary over time. To detect all four bases, four nanoribbons, each with a different base attached to the pore, could be stacked vertically to create an integrated DNA sensor. The molybdenum disulfide ribbon is flexible enough to deform measurably in response to the forces required to break up a DNA pair, but rigid enough to have less ongoing, meaningless movement than graphene, potentially reducing unwanted noise in the sequencing signals. The deflection of the ribbon is exceedingly small, on the order of one angstrom, the size of a hydrogen atom. Its pulling force is on the order of 50 piconewtons, or trillionths of a newton, enough to break up the delicate chemical bonds between DNA bases. Researchers estimated how the device would perform in an integrated circuit and found the peak currents through the capacitor were measurable (50 to 70 picoamperes), even for the small nanoribbons studied. The current peaks are expected to be even larger in physical systems. The device size could be tweaked to make it even easier to measure sequencing signals. The NIST authors hope to build a physical version of the device in the future. For practical applications, the chip-sized DNA sequencing microfluidic technology might be combined with electronics into a single device small enough to be handheld. Reference: RFCS04021000BJTT1 RFCS04025000DBTT1 SC02201518    

The availability of the MMC5883MA 3 Axis Magnetic Sensor has been announced by MEMSIC. The newest member of MEMSIC’s Anisotropic Magneto Resistive (AMR) based Magnetic Sensor family, it provides the industry’s highest accuracy, lowest noise and lowest power consumption. All combined in an industry standard small LGA package, and addresses the ever-increasing demands of industrial and drone applications.Dr. Yang Zhao, MEMSIC’s Chairman, President and CEO said: “With more than 300 million units shipped, MEMSIC has a long history of success with its AMR magnetic sensor in a wide range of critical portable and wearable applications. Integrating innovative design architecture and optimised processes, MEMSIC’s new 3-Axis, ± 8 Gauss Full Scale Range (FSR) MMC5883MA provides a reliable, high performance solution for industrial and drone system design and development engineers who need to provide stability and direction sensing for their designs.”The MEMSIC MMC5883MA 3-Axis Magnetic Sensor provides 16-bit operation over a wide ± 8 Gauss operating range with linearity of ±0.2 % FSR, hysteresis of 0.2 % FSR and repeatability of 0.2 % FSR on each of its 3-axis. Its exceptionally high performance enables faster algorithms for hard and soft iron interference correction delivering more precise and faster heading determination. The small, low profile LGA package measures 3.0x3.0x1.0 mm. and operates over the -40 to +85°C temperature range from a supply voltage of 2.16-3.6V. It exhibits extremely low current consumption of only 20uA at seven samples per second data rate and extremely low noise level of only 0.4mGauss total RMS noise making it ideal for drone and industrial markets.The MC5883MA is complete system incorporating on-chip signal processing and an integrated I2C 400kHz FAST mode operation digital interface for direct connectivity to the system microprocessor.The MEMSIC MMC5883MA 3-Axis Magnetic Sensor is available immediately and in production now. Devices pre-mounted on prototyping boards can be purchased directly from MEMSIC. Designers can evaluate and log data using MEMSIC's Universal Evaluation Board.Reference:TLE4976-2KAH180-WG-7AH1801-WG-7  

Researchers from the Institute for Biomedical Engineering have succeeded in measuring tiny changes in strong magnetic fields. In their experiments, the scientists magnetised a water droplet inside a magnetic resonance imaging (MRI) scanner, a device that is used for medical imaging. The researchers were able to detect even the tiniest variations of the magnetic field strength within the droplet.These changes were up to a trillion times smaller than the seven tesla field strength of the MRI scanner used in the experiment. “Until now, it was possible only to measure such small variations in weak magnetic fields,” says Klaas Prüssmann, Professor of Bioimaging at ETH Zurich and the University of Zurich.An example of a weak magnetic field is that of the Earth, where the field strength is just a few dozen microtesla. For fields of this kind, highly sensitive measurement methods are already able to detect variations of about a trillionth of the field strength, says Prüssmann.“Now, we have a similarly sensitive method for strong fields of more than one tesla, such as those used, inter alia, in medical imaging.” The scientists based the sensing technique on the principle of nuclear magnetic resonance, which also serves as the basis for magnetic resonance imaging and the spectroscopic methods that biologists use to elucidate the 3D structure of molecules.However, to measure the variations, the scientists had to build a new high-precision sensor, part of which is a highly sensitive digital radio receiver. “This allowed us to reduce background noise to an extremely low level during the measurements,” says Simon Gross. Gross wrote his doctoral thesis on this topic in Prüssmann’s group and is lead author of the paper published in the journal Nature Communications.In the case of nuclear magnetic resonance, radio waves are used to excite atomic nuclei in a magnetic field. This causes the nuclei to emit weak radio waves of their own, which are measured using a radio antenna; their exact frequency indicates the strength of the magnetic field.As the scientists emphasise, it was a challenge to construct the sensor in such a way that the radio antenna did not distort the measurements. The scientists have to position it in the immediate vicinity of the water droplet, but as it is made of copper it becomes magnetised in the strong magnetic field, causing a change in the magnetic field inside the droplet.The researchers therefore came up with a trick: they cast the droplet and antenna in a specially prepared polymer; its magnetisability (magnetic susceptibility) exactly matched that of the copper antenna. In this way, the scientists were able to eliminate the detrimental influence of the antenna on the water sample.This measurement technique for very small changes in magnetic fields allows the scientists to now look into the causes of such changes. They expect their technique to find use in various areas of science, some of them in the field of medicine, although the majority of these applications are still in their infancy.“In an MRI scanner, the molecules in body tissue receive minimal magnetisation – in particular, the water molecules that are also present in blood,” explains doctoral student Gross. “The new sensor is so sensitive that we can use it to measure mechanical processes in the body; for example, the contraction of the heart with the heartbeat.”The scientists carried out an experiment in which they positioned their sensor in front of the chest of a volunteer test subject inside an MRI scanner. They were able to detect periodic changes in the magnetic field, which pulsated in time with the heartbeat.The measurement curve is reminiscent of an electrocardiogram (ECG), but unlike the latter measures a mechanical process (the contraction of the heart) rather than electrical conduction.“We are in the process of analysing and refining our magnetometer measurement technique in collaboration with cardiologists and signal processing experts,” says Prüssmann. “Ultimately, we hope that our sensor will be able to provide information on heart disease – and do so non-invasively and in real time.”The new measurement technique could also be used in the development of new contrast agents for magnetic resonance imaging: in MRI, the image contrast is based largely on how quickly a magnetised nuclear spin reverts to its equilibrium state.Experts call this process relaxation. Contrast agents influence the relaxation characteristics of nuclear spins even at low concentrations and are used to highlight certain structures in the body.In strong magnetic fields, sensitivity issues had previously restricted scientists to measurement of just two of the three spatial nuclear spin components and their relaxation.They had to rely on an indirect measurement of relaxation in the important third dimension. For the first time, the new high-precision measurement technique allows the direct measurement of all three dimensions of nuclear spin in strong magnetic fields.Direct measurement of all three nuclear spin components also paves the way for future developments in nuclear magnetic resonance (NMR) spectroscopy for applications in biological and chemical research.