Development and optimization of a frequency mixing sensor for adjacent samples quantitative detection on a lateral flow assay.

Frequency-mixing technology has been widely used to precisely identify magnetic nanoparticles in applications of quantitative biomedical detection in recent years. Examples include immune adsorption, lateral flow assays (LFAs), and biomagnetic imaging. However, the signals of magnetic response generated by adjacent magnetic samples interfere with each other owing to the small spacing between them in applications involving multi-sample detection (such as the LFA and multiplexing detection). Such signal interference prevents the biosensor from obtaining characteristic peaks related to the concentration of adjacent biomarkers from the magnetic response signals. Mathematical and physical models of the structure of sensors based on frequency-mixing techniques were developed. The theoretical model was verified and its key parameters were optimized by using simulations. A new frequency-mixing magnetic sensor structure was then designed and developed based on the model, and the key technical problem of signal crosstalk between adjacent samples was structurally solved. Finally, standard cards with stable magnetic properties were used to evaluate the performance of the sensor, and strips of the gastrin-17 (G-17) LFA were used to evaluate its potential for use in clinical applications. The results show that the minimum spacing between samples required by the optimized sensor to accurately identify them was only about 4-5 mm, and the minimum detectable concentration of G-17 was 11 pg mL-1 . This is a significant reduction in the required spacing between samples for multiplexing detection. The optimized sensor also has the potential for use in multi-channel synchronous signal acquisition, and can be used to detect synchronous magnetic signals in vivo.

Grain Boundary Engineering Enabled High-Performance Garnet-Type Electrolyte for Lithium Dendrite Free Lithium Metal Batteries.

Solid-state lithium metal batteries (SSLMBs) are attracting increasing attentions as one of the promising next-generation technologies due to their high-safety and high-energy density. Their practical application, however, is hindered by lithium dendrite growth and propagation in solid-state electrolytes (SSEs). Herein, an in situ grain boundary modification strategy relying on the reaction between Li2 TiO3 (LTO) and Ta-substituted garnet-type electrolyte (LLZT) is developed, which forms LaTiO3 along with lesser amounts of LTO/Li2 ZrO3 at the grain boundaries (GBs). The second phases of LTO/Li2 ZrO3 inhibit abnormal grain growth. The presence of LaTiO3 at the GBs reduces electronic conductivity and improves mechanical strength, which can hinder dendrite formation and block lithium dendrite penetration through the LLZT. Moreover, the adjacent grains by LaTiO3 build a continuous Li+ transport path, providing a homogeneous Li+ flux throughout the whole LLZT-4LTO. As a result, symmetric cells of Li | LLZT-4LTO | Li shows a high critical current density of 1.8 mA cm-2 and a long cycling stability up to 2000 h at 0.3 mA cm-2 . Moreover, the high-voltage full cells demonstrate remarkable cycling stability and rate performance. It is believed that this novel grain boundary modification strategy can shed light on the constructing of high-performance SSEs for practical SSLMBs.

Can wastewater surveillance assist China to cost-effectively prevent the nationwide outbreak of COVID-19?

China has controlled the nationwide spread of COVID-19 since April 2020, but it is still facing an enormous threat of disease resurgence originating from infected international travelers. Taking the rapid transmission and the mutation of SARS-CoV-2 into consideration, the current status would be easily jeopardized if sporadic locally-transmitted individuals are not identified at an early stage. Clinical diagnosis is the gold standard for COVID-19 surveillance, but it is hard to screen presymptomatic or asymptomatic cases in those who have not exhibited symptoms. Since presymptomatic or asymptomatic individuals are infectious, it is urgent to establish a surveillance system based on other tools that can profile the entire population. Infected people including those who are symptomatic, presymptomatic, and asymptomatic shed SARS-CoV-2 RNA in feces and thereby endow wastewater-based epidemiology (WBE) with an early-warning ability for mass COVID-19 surveillance. In the context of China's "COVID-zero" strategy, this work intends to discuss the practical feasibility of WBE applications as an early warning and disease surveillance system in hopes that WBE together with clinical testing would cost-effectively restrain sporadic COVID-19 outbreaks in China.

Nanozyme enhanced magnetic immunoassay for dual-mode detection of gastrin-17.

In this study, we developed a novel magnetic lateral flow assay based on iron oxide decorated with platinum probes (Fe3O4@Pt) for dual-mode detection of gastrin-17 (G-17), which is one of the main biomarkers for early gastric cancer diagnosis. The probe material exhibits both magnetic properties and peroxidase activity. The peroxidase activity enhances the intensity of the brownish coloring of the Fe3O4@Pt probes on the test strip, with a limit of detection of 10 pg mL-1 using the naked eye, which is remarkable for colorimetric lateral flow assays. The magnetic property allows the simple separation and enrichment of the sample, and the signal can be read using a magnetic assay reader for quantitative detection. The linear range for G-17 using the magnetic signal was determined as 10 pg mL-1 to 2200 pg mL-1, and the calculated limit of detection was as low as 3.365 pg mL-1, thereby covering the reference range for G-17. Serum samples were used to validate the test strip, which exhibited high sensitivity, high specificity, and consistency with the results obtained by the enzyme-linked immunosorbent assay method. The entire inspection process using this method can produce results within 35 min and it is simple to operate without requiring strict experimental conditions. This dual-mode lateral flow test strip provides a simple, rapid, and quantitative strategy for detecting G-17, and it may also be valuable in other portable diagnostic applications.

Magnetic frequency mixing technological advances for the practical improvement of point-of-care testing.

Nanomaterials, especially superparamagnetic nanomaterials, have recently played essential roles in point-of-care testing due to their intrinsic magnetic, electrochemical, and optical properties. The inherent superparamagnetism of magnetic nanoparticles makes them highly sensitive for quantitative detection. Among the various magnetic detection technologies, frequency mixing technology (FMT) technology is an emerging detection technique in the nanomedical field. FMT sensors have high potential for development in the field of biomedical quantitative detection due to their simple structure, and they are not limited to the materials used. In particular, they can be applied for large-scale disease screening, early tumor marker detection, and low-dose drug detection. This review summarizes the principles of FMT and recent advances in the fields of immunoadsorption, lateral flow assay detection, magnetic imaging, and magnetic nanoparticles recognition. The advantages and limitations of FMT sensors for robust, ultrasensitive biosensing are highlighted. Finally, the future requirements and challenges in the development of this technology are described. This review provides further insights for researchers to inspire the future development of FMT by integration into biosensing and devices with a broad field of applications in analytical sensing and clinical usage.

Strategies for the detection of target analytes using microfluidic paper-based analytical devices.

Microfluidic paper-based analytical devices (µPADs) have developed rapidly in recent years, because of their advantages, such as small sample volume, rapid detection rates, low cost, and portability. Due to these characteristics, they can be used for in vitro diagnostics in the laboratory, or in the field, for a variety of applications, including food evaluation, disease screening, environmental monitoring, and drug testing. This review will present various detection methods employed by µPADs and their respective applications for the detection of target analytes. These include colorimetry, electrochemistry, chemiluminescence (CL), electrochemiluminescence (ECL), and fluorescence-based methodologies. At the same time, the choice of labeling material and the design of microfluidic channels are also important for detection results. The construction of novel nanocomponents and different smart structures of paper-based devices have improved the performance of µPADs and we will also highlight some of these in this manuscript. Additionally, some key challenges and future prospects for the use of µPADs are briefly discussed.

Rapid developments in lateral flow immunoassay for nucleic acid detection.

Recently, lateral flow assay (LFA) for nucleic acid detection has drawn increasing attention in the point-of-care testing fields. Due to its rapidity, easy implementation, and low equipment requirement, it is well suited for use in rapid diagnosis, food authentication, and environmental monitoring under source-limited conditions. This review will discuss two main research directions of lateral flow nucleic acid tests. The first one is the incorporation of isothermal amplification methods with LFA, which ensures an ultra-high testing sensitivity under non-laboratory conditions. The two most commonly used methodologies will be discussed, namely Loop-mediated Isothermal Amplification (LAMP) and Recombinase Polymerase Amplification (RPA), and some novel methods with special properties will also be introduced. The second research direction is the development of novel labeling materials. It endeavors to increase the sensitivity and quantifiability of LFA testing, where signals can be read and analyzed by portable devices. These methods are compared in terms of limits of detection, detection times, and quantifiabilities. It is anticipated that future research on lateral flow nucleic acid tests will focus on the integration of the whole testing process into a microfluidic system and the combination with molecular diagnostic tools such as clustered regularly interspaced short palindromic repeats to facilitate a rapid and accurate test.

Holographic particle sizing and locating by using Hilbert-Huang transform.

By using the Hilbert-Huang transform, a novel method is proposed to perform the task of particle sizing and axial locating directly from in-line digital holograms rather than reconstructing the optical field. The intensity distribution of the particle hologram is decomposed into intrinsic mode functions (IMFs) by the empirical mode decomposition. From the Hilbert spectrum of these IMFs, the axial location of the particle can be calculated by fitting the spectrum to a straight line, and the particle size can be derived from the singularities of the spectrum. Our method does not need to predefine any basis function; thus the whole process is fast and efficient. The validity and accuracy of the method are demonstrated by the numerical simulations and experiments. It is expected that this method can be used in on-line particle sizing and 3D tracking.

Effects of structural periodicity on localization length in one-dimensional periodic-on-average disordered systems.

We investigate the effects of structural periodicity on wave localization in one-dimensional periodic-on-average disordered systems and derive two relations from the properties of the spectral periodicity and symmetry of the underlying periodic systems. These two relations predict equal localization lengths between disordered systems with different randomness. Comparisons with numerically simulated results show good agreement. These relations are used to explain some properties of the frequency dependence of the localization length, such as oscillation, asymmetry, etc.