Unlocking the Molecular Variations of a Micron-Scale Amyloid Plaque in an Early Stage Alzheimer's Disease by a Cellular-Resolution Mass Spectrometry Imaging Platform.

Uncovering the molecular changes at the site where Aß is deposited plays a critical role in advancing the diagnosis and treatment of Alzheimer's disease. However, there is currently a lack of a suitable label-free imaging method with a high spatial resolution for brain tissue analysis. In this study, we propose a modified desorption electrospray ionization (DESI) mass spectrometry imaging (MSI) method, called segmented temperature-controlled DESI (STC-DESI), to achieve high-resolution and high-sensitivity spatial metabolomics observation by precisely controlling desorption and ionization temperatures. By concentrating the spray plume and accelerating solvent evaporation at different temperatures, we achieved an impressive spatial resolution of 20 µm that enables direct observation of the heterogeneity around a single cell or an individual Aß plaque and an exciting sensitivity that allows a variety of low-abundance metabolites and less ionizable neutral lipids to be detected. We applied this STC-DESI method to analyze the brains of transgenic AD mice and identified molecular changes associated with individual Aß aggregates. More importantly, our study provides the first evidence that carnosine is significantly depleted and 5-caffeoylquinic acid (5-CQA) levels rise sharply around Aß deposits. These observations highlight the potential of carnosine as a sensitive molecular probe for clinical magnetic resonance imaging diagnosis and the potential of 5-CQA as an efficient therapeutic strategy for Aß clearance in the early AD stage. Overall, our findings demonstrate the effectiveness of our STC-DESI method and shed light on the potential roles of these molecules in AD pathology, specifically in cellular endocytosis, gray matter network disruption, and paravascular Aß clearance.

Reactive Matrices for MALDI-MS of Cholesterol.

Cholesterol is a critical molecule whose dysregulation in certain brain regions is related to multiple neurological disorders. It is of pathological importance to map the distribution of cholesterol in brain. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been widely used in the molecular imaging of metabolites at a high spatial resolution. However, it is challenging to analyze cholesterol by MALDI-MS due to its difficulty in ionization. Herein, we present for the first time a type of reactive matrix for MALDI-MS of cholesterol. Methylpyridinium carboxaldehydes react with cholesterol and other hydroxyl-containing sterols, which greatly enhanced both desorption and ionization and improved the limits of detection to the low µg/mL range. Compared with previous methods, our reactive matrix requires only one step of chemical derivatization and avoids time-consuming enzymatic reaction, which simplified the sample pretreatment. The reactive matrix was successfully used in mapping the distribution of cholesterol in brain tissue sections using MALDI-MS imaging. In summary, this work has provided a sensitive and simple method for the MALDI-MS analysis of cholesterol, has proposed a novel solution to visualize the distribution of sterol metabolites, and has great potential for applications in neurological and pathological studies.

Structural Electronic Skin for Conformal Tactile Sensing.

The conformal integration of the electronic skin on the non-developable surface is in great demand for the comprehensive tactile sensing of robotics and prosthetics. However, the current techniques still encounter obstacles in achieving conformal integration of film-like electronic skin on non-developable surfaces with substantial curvatures for contact pressure detection and tactile mapping. In this paper, by utilizing the 3D printing technology to prepare the 3D electrode array in the structural component following its surface curvature, and covering it with a molded functional shell to form the pressure sensitive iontronic interface, a device is proposed to achieve high-sensitive pressure detection and high-fidelity tactile mapping on a complicated non-developable surface, called structural electronic skin (SES). The SES is prepared in a 3D printed fingertip with 46 tactile sensing units distributed on its curved surface, achieving the integration of both structural and tactile functions in a single component. By integrating the smart fingertip into a dexterous hand, a series of demonstrations are presented to show the dead-zone free pressure detection and tactile mapping with high sensitivity, for instance, 2D pulse wave monitoring and robotic injection in a medical robot, object recognition and compliant control in a smart prosthesis.

Blink-sensing glasses: A flexible iontronic sensing wearable for continuous blink monitoring.

Blink reflex has long been considered closely related to physiological states, from which abundant information on ocular health and activities can be revealed. In this study, a smart glasses wearable has been developed, incorporating a flexible and sensitive pressure sensor, to monitor blink patterns by continuously detecting ocular muscular movements, referred to as blink-sensing glasses. By applying the emerging flexible iontronic sensing (FITS) sensor with the sensitivity of 340 pF/mmHg, the skin pressure variations induced by movements of the orbicularis oculi muscles can be monitored in real time. The blink-sensing glasses can successfully capture blink patterns with a high accuracy of 96.3% and have been used to differentiate the blink features from both dry-eye subjects and healthy controls. This device can be potentially used as a new clinical and research monitoring tool for continuous eye blink analysis, while providing patients with high comfortableness in long-term ambulatory and home settings.

Microfluidic cap-to-dispense (µCD): a universal microfluidic-robotic interface for automated pipette-free high-precision liquid handling.

Microfluidic devices have been increasingly used for low-volume liquid handling operations. However, laboratory automation of such delicate devices has lagged behind due to the lack of world-to-chip (macro-to-micro) interfaces. In this paper, we have presented the first pipette-free robotic-microfluidic interface using a microfluidic-embedded container cap, referred to as a microfluidic cap-to-dispense (µCD), to achieve a seamless integration of liquid handling and robotic automation without any traditional pipetting steps. The µCD liquid handling platform offers a generic and modular way to connect the robotic device to standard liquid containers. It utilizes the high accuracy and high flexibility of the robotic system to recognize, capture and position; and then using microfluidic adaptive printing it can achieve high-precision on-demand volume distribution. With its modular connectivity, nanoliter processability, high adaptability, and multitask capacity, µCD shows great potential as a generic robotic-microfluidic interface for complete pipette-free liquid handling automation.