Low-cost Nuclear Magnetic Resonance Research Articles

Efficient Xe Filling of MEMS Vapor Cells Empowered by Customized Triple Stack Wafer Bond Processing

Nuclear-magnetic-resonance (NMR) gyroscopes based on MEMS vapor cell technology are currently being investigated worldwide and show superior advantages over current MEMS gyroscopes. However, there are still challenges in the upscaling and further deployment of NMR gyroscopes, due to the extremely high cost of the required gases (i.e. 129Xe, 131Xe), size, and high power consumption. To tackle these bottlenecks, in this study, a miniaturized, chip-scale, and low-cost NMR gyroscope has been conceptualized and fabricated. Here, a cost-effective and scalable filling of MEMS vapor cells with isotropic Xe filling was developed via an innovative microfabrication and wafer stacking process flow. By utilizing ultra-thin glass wafers, Taiko-processed silicon wafers, and an external gas flow system integrated into the wafer bonders, a sequential anodic bonding technique was executed to create a hermetically sealed chamber through which Xe gas can flow in a minimal volume. Fig. 1 shows the configuration of the triple-stack bonded wafer featuring the sealed chamber, the gas inlet, and the outlet. The Xe mass flow rate during the efficient filling process was 3.2528 *10-7 kg/s with a total filling time of <100 sec, as verified by the two-way Fluid-Structure Interactions (FSI) simulation data. As a result, it was demonstrated that the consumption of Xe gas during device filling can be dramatically reduced, which has a substantial impact on the total cost of the MEMS vapor cell. Figure 1. A demonstration of the triple-stack bonded wafer (glass-Silicon-glass) with an efficient Xe gas-filling process Figure 1

Efficient Xe Filling of MEMS Vapor Cells Empowered by Customized Triple Stack Wafer Bond Processing

Nuclear-magnetic-resonance (NMR) gyroscopes based on MEMS vapor cell technology are currently being investigated worldwide and show superior advantages over current MEMS gyroscopes. However, there are still challenges in the upscaling and further deployment of NMR gyroscopes, due to the extremely high cost of the required gases (i.e., 129Xe, 131Xe), size, and high power consumption. To tackle these bottlenecks, in this study, a miniaturized, chip-scale, and low-cost NMR gyroscope has been conceptualized and fabricated. Here, a cost-effective and scalable filling of MEMS vapor cells with Xe gas was developed via an innovative microfabrication and wafer stacking process flow. By utilizing ultra-thin glass wafers, Taiko-processed silicon wafers, and an external gas flow system integrated into the wafer bonder, a sequential anodic bonding technique is executed to create a hermetically sealed Xe gas-filled chamber at minimal Xe consumption during the filling process.

#5650 METABOLIC BLOOD BIOMARKER PROFILING FOR CHRONIC KIDNEY DISEASE PREDICTION – EVIDENCE FROM 275,000 INDIVIDUALS IN THE UK BIOBANK

Abstract Background and Aims Early identification of individuals at high risk of developing chronic kidney disease and other chronic conditions is essential for targeted prevention. Here, we assess the utility of metabolic blood biomarkers in predicting the onset of chronic kidney disease in over 250,000 individuals from UK Biobank, beyond established risk factors and polygenic risk scores. Method Circulating blood biomarkers, including lipids, fatty acids, amino acids, glycolysis metabolites and inflammation markers were measured by a low-cost nuclear magnetic resonance (NMR) metabolomics assay in around 275,000 plasma samples from the UK Biobank. During a prospective 10-year follow-up, over 6000 incident chronic kidney disease events were obtained from national health registries. Using multivariable regression modelling, we derived a 10-year risk score for chronic kidney disease onset. We assessed the predictive performance of the biomarker risk score in comparison to standard risk factors (age, sex, prevalent diabetes, body mass index, systolic and diastolic blood pressure, smoking status and use of cholesterol lowering medication), clinical chemistry measurements (HbA1c, LDL and HDL cholesterol, total cholesterol and eGFR) and polygenic risk scores. We evaluated the performance of the risk score in two practical scenarios: in a general population screening setting and in a clinical use case of stratifying kidney disease risk among prevalent type 2 diabetics. We further illustrate applications of the biomarker risk scores in predicting the risk of other chronic diseases, such as cardiovascular outcomes, in general population settings. Results In the general population screening setting, adding the metabolic biomarkers to a simple model of standard risk factors substantially improved the predictive performance, with area under the receiver operating characteristic curve (AUC) increasing from 0.74 to 0.82. When compared to more comprehensive model including also clinical chemistry measurements and polygenic risk scores, the improvements were also significant, albeit more modest, with the AUC increasing from 0.81 to 0.83. Even more substantial gains were observed in a clinical use case scenario of stratifying risk of chronic kidney disease onset among prevalent type 2 diabetics. Among diabetics with mildly to moderately decreased kidney function at the time of blood sampling (eGFR 60-90), adding the metabolic biomarkers in a comprehensive model including standard risk factors, clinical chemistry measurements and polygenic risk scores increased the AUC from 0.60 to 0.70. Conclusion Circulating metabolic biomarkers enhanced the prediction of chronic kidney disease onset beyond standard risk factors and polygenic risk scores. From a translational perspective, this may complement the identification of high-risk individuals in both general population and clinical settings beyond current risk factor assessment, while simultaneously informing on the risk of other chronic diseases.

Discrimination between softwood and hardwood based on hemicellulose content obtained with portable nuclear magnetic resonance

Wood is a hygroscopic material that can reach an equilibrium moisture content when ambient temperature and relative humidity are constant. Moisture affects all properties of wood, as well as its preservative treatment. The hygroscopic behavior of wood can be attributed to the hydroxyl groups of its constituents. Since hemicellulose shows the greatest water affinity, it can be considered the main responsible for the ingress of water into the wood mass. Below the fiber saturation point, wood moisture is only stored in the cell walls. Proton Nuclear Magnetic Resonance (NMR) is a relative method used for the evaluation of moisture content distribution in wood and NMR relaxation is an excellent tool to study the hygroscopic behavior of different woods below the fiber saturation point. This work aimed to test the hypothesis of discriminating among softwoods and hardwoods of different botanical species and identifying further sub-clusters of woods based on the NMR proton spin–spin (T2) and spin–lattice (T1) relaxation times of their cell wall water in the hygroscopic moisture range. Importantly, the study was performed using a portable low-cost NMR instrument with which it is possible to investigate wood samples of any size. The main result of this study was that at RH = 94% the relaxation time T2,2, associated with the cell wall bound water, can be used as a marker to discriminate among softwoods and hardwoods.Graphical abstract

Stable magic angle spinning with Low-Cost 3D-Printed parts

A 3D-printed double-bearing magic angle spinning (MAS) system was developed with a home-built 4.0 mm MAS nuclear magnetic resonance (NMR) probe at 7 T. Various fused deposition modelling 3D printers were used to produce spinning modules of ignorable materials costs for rotors with a diameter of 7.0, 4.0, and 3.5 mm. High-performance MAS experiments on the 4.0 mm-diameter model using a pencil-type ceramic rotor and 3D-printed drive cap resulted in a high-resolution 1H NMR signal of silicone grease. The 3.5 mm-diameter MAS system reached a spinning frequency of 23 kHz. Furthermore, 3D-printed inserts were designed for various rotor sizes which can isolate the sample from humidity for a duration of more than a week. Single crystal inserts for MAS rotors of commercial probes can readily be printed using two-color printers. Those developments enable customized low-cost MAS NMR for both adapting existing and manufacturing new probes, respectively.

Incorporation of Benchtop NMR Spectrometer into the Organic Chemistry Laboratory: Analysis of an Unknown Liquid

Nuclear magnetic resonance (NMR) spectroscopy is an indispensable technique in the organic chemistry laboratory for elucidation of molecular structure. Miniaturization of NMR technology has attracted attention and acceptance due to a considerable reduction in the cost to acquire and maintain the instrument. The advent of low-field, low-cost, and low-maintenance tabletop NMR technology has provided academic institutions with limited resources the option of hands-on NMR experimentation for undergraduates. The application of the tabletop NMR instrument in the organic chemistry laboratory to analyze an unknown liquid, which can be an ester, an aldehyde, an alcohol, or a ketone, together with infrared (IR) spectroscopy and classic chemical color tests, is herein described.

Ultrasensitive and fast detection of pathogens using Europium-containing polystyrene nanospheres in a homemade portable NMR diagnostic system

The use of nuclear magnetic resonance (NMR) platforms to detect biological samples via magnetic nanoparticles has shown great importance in clinical applications. In numerous studies, superparamagnetic nanoparticles, including ferromagnetic nanoparticles, have been adopted to improve the performance of magnetic nanoparticles. Here we developed a simple and novel europium (Eu)-containing polystyrene nanosphere (PS NS)-based NMR system for rapid pathogen detection in clinical samples. Using this proposed portable NMR diagnostic system, we found that during pathogen detection, NPs with lower susceptibility (e.g., Eu-containing PS NSs) produced an unexpected detection effect compared with iron oxide NPs. Our Eu-containing PS NS-based NMR diagnostic system showed higher detection sensitivity, broader detection range, and higher stability than conventional iron oxide NP-based NMR platforms do. Using an inexpensive microcontact-printed Ag microcoil-based NMR probe, we demonstrated unprecedented detection sensitivity and speed with minimal sample preparation for pathogen analyses. The sample concentration of 0.2 ng/mL of hepatitis B virus surface antigen (HBsAg) and 10 CFU/mL of Clostridium difficile can be attained by the NMR diagnostic system within 5 s, and concentration-detection ranges spanned over three orders of magnitude. With advantages of low-cost NMR probe, a portable instrument, and convenient operation, our proposed NMR platform may provide a promising point-of-care diagnostic system in clinical applications.

In Situ SABRE Hyperpolarization with Earth’s Field NMR Detection

Hyperpolarization methods, which increase the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI), have the potential to expand the range of applications of these powerful analytical techniques and to enable the use of smaller and cheaper devices. The signal amplification by reversible exchange (SABRE) method is of particular interest because it is relatively low-cost, straight-forward to implement, produces high-levels of renewable signal enhancement, and can be interfaced with low-cost and portable NMR detectors. In this work, we demonstrate an in situ approach to SABRE hyperpolarization that can be achieved using a simple, commercially-available Earth’s field NMR detector to provide 1H polarization levels of up to 3.3%. This corresponds to a signal enhancement over the Earth’s magnetic field by a factor of ε > 2 × 108. The key benefit of our approach is that it can be used to directly probe the polarization transfer process at the heart of the SABRE technique. In particular, we demonstrate the use of in situ hyperpolarization to observe the activation of the SABRE catalyst, the build-up of signal in the polarization transfer field (PTF), the dependence of the hyperpolarization level on the strength of the PTF, and the rate of decay of the hyperpolarization in the ultra-low-field regime.

A CMOS differential receiver dedicated to nuclear magnetic resonance applications

This paper examines the design and implementation of a 21 MHz CMOS differential or so-called dual-path receiver (DPR) dedicated to nuclear magnetic resonance (NMR) spectrometer. This receiver features a CMOS chip incorporated with two mini-Coils and other circuitries. Herein we discuss the design and implementation of the DPR chip as the core part of this new NMR system. The DPR consists of two differential low-noise amplifiers, voltage buffers, phase shifters and variable gain amplifiers in order to accurately cancel the effect of the background NMR signal. We put forward the design and analysis of the DPR chip and thereafter demonstrate and discuss the simulation and experimental results. Based on these results, the front-end receiver achieves a voltage gain of 80 dB at a low input referred noise of 2.7 nV/?Hz. The chip is designed in a 0.13-µm CMOS technology and occupies an area of 1 mm × 2 mm. As per experimental results, this device can be used n the future low-cost NMR technologies.

Small NMR biomolecular sensors

By combining the physics of nuclear magnetic resonance (NMR) and silicon radio-frequency (RF) integrated circuits, we recently created progressively smaller NMR systems, which we originally reported in Refs. [1–4]. Our strategy for NMR system miniaturization proved effective, culminating in the smallest prototype [3,4] that weighs 0.1kg and can be held at the palm of the hand. These small, low-cost NMR systems can be useful as biomolecular sensors in the personalized medicine setting, and we demonstrated their ability to detect proteins, compounds, and human cancer cells. The present paper, which is not a new technical contribution, reviews these developments.

Portable, low-cost NMR with laser-lathe lithography produced microcoils

Nuclear Magnetic Resonance (NMR) is unsurpassed in its ability to non-destructively probe chemical identity. Portable, low-cost NMR sensors would enable on-site identification of potentially hazardous substances, as well as the study of samples in a variety of industrial applications. Recent developments in RF microcoil construction (i.e. coils much smaller than the standard 5 mm NMR RF coils), have dramatically increased NMR sensitivity and decreased the limits-of-detection (LOD). We are using advances in laser pantographic microfabrication techniques, unique to LLNL, to produce RF microcoils for field deployable, high sensitivity NMR-based detectors. This same fabrication technique can be used to produce imaging coils for MRI as well as for standard hardware shimming or “ex-situ” shimming of field inhomogeneities typically associated with inexpensive magnets. This paper describes a portable NMR system based on the use of a 2 kg hand-held permanent magnet, laser-fabricated microcoils, and a compact spectrometer. The main limitations for such a system are the low resolution and sensitivity associated with the low field values and quality of small permanent magnets, as well as the lack of large amounts of sample of interest in most cases. The focus of the paper is on the setting up of this system, initial results, sensitivity measurements, discussion of the limitations and future plans. The results, even though preliminary, are promising and provide the foundation for developing a portable, inexpensive NMR system for chemical analysis. Such a system will be ideal for chemical identification of trace substances on site.

Low-cost high-temperature NMR probe head

The design of a simple high-temperature nuclear magnetic resonance (NMR) probe head for narrow-bore magnets is presented. It covers the temperature range from 20 to 1300°C, necessitating a heating power of below 100 W. Several probe heads of this design, manufactured for NMR solenoids with bores from 30 to 54 mm have shown good stability and long life times.

Simulation of nuclear magnetic resonance spin echoes using the Bloch equation: Influence of magnetic field inhomogeneities

There are a number of low cost nuclear magnetic resonance (NMR) applications that are based on measurements of spin-spin (T2) and spin-lattice (T1) relaxation times. Pulsed rf magnetic fields are typically used to flip the nuclear spins in these measurements. The ability to perform these measurements in relatively nonuniform magnetic fields is a factor in minimizing costs. In this work, we explore the limitations of field inhomogeneity on spin echo techniques for measuring relaxation times. Using a computer model that was developed for this study, we numerically integrate the Bloch equation to simulate spin echo peaks for CPMG and other pulse sequences. We quantify how higher intensity rf pulses result in increased amplitudes of spin echo peaks in an inhomogeneous static magnetic field. An rf amplitude which is five times the maximum inhomogeneity in the static field results in less than 0.5% attenuation between even numbered peaks in a CPMG sequence.