Using Functionalized Liposomes to Harvest Extracellular Vesicles of Similar Characteristics in Dermal Interstitial Fluid.

Extracellular vesicles (EVs) are used by living cells for the purpose of biological information trafficking from parental-to-recipient cells and vice versa. This back-and-forth communication is enabled by two distinct kinds of biomolecules that constitute the cargo of an EV: proteins and nucleic acids. The proteomic-cum-genetic information is mediated by the physiological state of a cell (healthy or otherwise) as much as modulated by the biogenesis pathway of the EV. Therefore, in mirroring the huge diversities of human communications, the proteins and nucleic acids involved in cell communications possess seemingly near limitless diversities, and it is this characteristic that makes EVs so highly heterogeneous. Currently, there is no simple and reliable tool for the selective capture of heterogeneous EVs and the delivery of their undamaged cargo for research in extracellular protein mapping and spatial proteomics studies. Our work is a preliminary attempt to address this issue. We demonstrated our approach by using antibody functionalized liposomes to capture EVs from tumor and healthy cell-lines. To characterize their performance, we presented fluorescence and nanoparticle tracking analysis (NTA) results, TEM images, and Western blotting analysis for EV proteins. We also extracted dermal interstitial fluid (ISF) from healthy individuals and used our functionalized synthetic vesicle (FSV) method to capture EVs from their proteins. We constructed three proteomic sets [EV vs ISF, (FSV+EV) vs ISF, and (FSV+EV) vs EV] from the EV proteins and the free proteins harvested from ISF and compared their differentially expressed proteins (DEPs). The performance of our proposed method is assessed via an analysis of 1095 proteins, together with volcano plots, heatmap, GO annotation, and enriched KEGG pathways and organelle localization results of 213 DEPs.

Wireless, battery-free and wearable device for electrically controlled drug delivery: sodium salicylate released from bilayer polypyrrole by near-field communication on smartphone.

Compared with traditional drug delivery methods, transdermal drug delivery has many advantages in avoiding the side effects in gastrointestinal tract, reducing the fluctuations in drug concentration, and improving patients' compliance. Among them, electrically controlled drug delivery is a promising solution. This work presents a wireless, battery-free and wearable device with electrically controlled drug delivery capability. The electronic component of the device is a flexible circuit board with a temperature sensor and a near-field communication module. With the help of smartphone, the device could wirelessly obtain energy and implement data transmission. The drug delivery component is a paper-based electrode modified with polypyrrole, in which non-steroidal anti-inflammatory drug sodium salicylate was encapsulated. The applied potential for electrically controlled drug delivery was more negative than -0.6 V. The drug release dose and release rates could be controlled by applying potentials with different amplitudes and durations through this device. It provided a minimalized wearable transdermal drug delivery platform for monitoring diseases such as gout. This wearable device shows promising potential in develop closed-loop drug delivery and monitoring systems for the treatment of various diseases.

Salivary Cortisol Determination on Smartphone-Based Differential Pulse Voltammetry System.

Cortisol is commonly used as a significant biomarker of psychological or physical stress. With the accelerated pace of life, non-invasive cortisol detection at the point of care (POC) is in high demand for personal health monitoring. In this paper, an ultrasensitive immunosensor using gold nanoparticles/molybdenum disulfide/gold nanoparticles (AuNPs/MoS2/AuNPs) as transducer was explored for non-invasive salivary cortisol monitoring at POC with the miniaturized differential pulse voltammetry (DPV) system based on a smartphone. Covalent binding of cortisol antibody (CORT-Ab) onto the AuNPs/MoS2/AuNPs transducer was achieved through the self-assembled monolayer of specially designed polyethylene glycol (PEG, SH-PEG-COOH). Non-specific binding was avoided by passivating the surface with ethanolamine. The miniaturized portable DPV system was utilized for human salivary cortisol detection. A series current response of different cortisol concentrations decreased and exhibited a linear range of 0.5-200 nM, the detection limit of 0.11 nM, and high sensitivity of 30 µA M-1 with a regression coefficient of 0.9947. Cortisol was also distinguished successfully from the other substances in saliva. The recovery ratio of spiked human salivary cortisol and the variation of salivary cortisol level during one day indicated the practicability of the immunosensor based on the portable system. The results demonstrated the excellent performance of the smartphone-based immunosensor system and its great potential application for non-invasive human salivary cortisol detection at POC.

[Development of a New Type Elastic Syndesmosis Hook Plate].

OBJECTIVE: To design a kind of internal fixation device to treat the syndesmosis injury. METHODS: The elastic syndesmosis hook plate is made of medical stainless steel alloy, which is consisted of locking or common screw fixing hole of the tibial side for the head, tridentate fork like arc anatomical fibula side plate for the tail and serpentine elastic connecting body. By reduction of the joint of the lower tibia and fibula, the steel plate tail is fixed at the side of the fibula and the head is fixed at the side of the tibia for fixing the symphysis. RESULTS: The design of elastic syndesmosis hook plate is reasonable, and the operation is convenient. There is no need to penetrate the substantia ossea and the plate has elastic micro-movement feature, the problem of internal fixation breakage and loosening is avoid in huge degree, so it is safe and reliable. CONCLUSION: The elastic syndesmosis hook plate is a new type medical apparatus of internal fixation of the symphysis, which is worthy of clinical popularization and application.

Hydrogel-based radio frequency H2S sensor for in situ periodontitis monitoring and antibacterial treatment.

Periodontitis, a chronic disease, can result in irreversible tooth loss and diminished quality of life, highlighting the significance of timely periodontitis monitoring and treatment. Meanwhile, hydrogen sulfide (H2S) in saliva, produced by pathogenic bacteria of periodontitis, is an important marker for periodontitis monitoring. However, the easy volatility and chemical instability of the molecule pose challenges to oral H2S sensing. Here, we report a wearable hydrogel-based radio frequency (RF) sensor capable of in situ H2S detection and antibacterial treatment. The RF sensor comprises an agarose hydrogel containing conjugated silver nanoparticles-chlorhexidine (AG-AgNPs-CHL hydrogel) integrated with split-ring resonators. Adhered to a tooth, the hydrogel-based RF sensor enables wireless transmission of sensing signals to a mobile terminal and a concurrent release of the broad-spectrum antibacterial agent chlorhexidine without complex circuits. With the selective binding of the AgNPs to the sulfidion, the RF sensor demonstrates good sensitivity, a wide detection range (2-30 µM), and a low limit of detection (1.2 µM). Compared with standard H2S measurement, the wireless H2S sensor can distinguish periodontitis patients from healthy individuals in saliva sample tests. The hydrogel-based wearable sensor will benefit patients with periodontitis by detecting disease-related biomarkers for practical oral health management.

Wireless, noninvasive therapeutic drug monitoring system for saliva measurement toward medication management of schizophrenia.

As an efficient patient management tool of precision medicine, decentralized therapeutic drug monitoring (TDM) provides new vision for therapy adherence and health management of schizophrenia in a convenient manner. To dispense with psychologically burdensome blood sampling and to achieve real-time, noninvasive, and continual circulating tracking of drugs with narrow therapeutic window, we study the temporal metabolism of clozapine, an antipsychotic with severe side effect, in rat saliva by a wireless, integrated and patient-friendly smart lollipop sensing system. Highly sensitive and efficient sensing performance with acceptable anti-biofouling property was realized based on the synergistic effect of electrodeposited reduced graphene oxide and ionic liquids in pretreatment-free saliva with low detection limit and good accuracy cross-validated with conventional method. On this basis, continual salivary drug levels with distinctive pharmacokinetics were found in different routes of drug administration. Pilot experiment reveals a strong correlation between blood and saliva clozapine and a positive relationship between drug dosage and salivary drug level, indicating potential applications presented by noninvasive saliva analysis towards patient-centered and personalized pharmacotherapy and adherence management via proposed smart lollipop system.

Nanoplasmonic biosensor: coupling electrochemistry to localized surface plasmon resonance spectroscopy on nanocup arrays.

The nanoscale Lycurgus cup arrays were hybrid structures of nanocups and nanoparticles with ultrasensitivity to refractive index change. In this study, an electrochemical localized surface plasmon resonance (LSPR) sensor was developed by coupling electrochemistry to LSPR spectroscopy measurement on the nanoscale cup arrays (nanoCA). Based on the combination of electrochemistry and LSPR measurement, the electrochemical LSPR on nanoCA was observed with significant resonance wavelength shifts in electrochemical modulation. The synchronous implementation of cyclic voltammetry and optical transmission spectrum can be used to obtain multiply sensing information and investigate the enhancement for LSPR from electrochemical scanning. The electrochemical enhanced LSPR was utilized as biosensor to detect biomolecules. The electrochemical LSPR biosensor with synchronous electrochemical and optical implement showed higher sensitivity than that of conventional optical LSPR measurement. Detecting with multi-transducer parameters and high sensitivity, the electrochemical LSPR provided a promising approach for chemical and biological detection.