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On-Chip Octanol-Assisted Liposome Assembly for Bioengineering

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Trends in Cerebrovascular Disease-Related Mortality and Disparities in the United States: A 25-Year National Cross-Sectional Analysis

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Wageningen University & Research

Wannan Medical University

Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compound characterization and identification are being hampered by the lack of a comprehensive database of known compounds against which to compare experimental data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no standard format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have associated structure files (e.g., MOL, InChI, or SMILES), instead containing images of structures. This makes extraction and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24 594 compounds and contains referenced data for structure, compound names, source organisms, isolation references, total syntheses, and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and physical properties. The Web site also provides mechanisms for visualizing natural products chemical space and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Minimum Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Molecular Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms and is the first comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries.

The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discovery.

Microfluidic paper-based analytical devices (μPADs) have been widely explored for point-of-care testing due to their simplicity, low cost, and portability. μPADs with multiple-step reactions usually require precise flow control, especially flow-delay. This paper reports the numerical, mathematical, and experimental studies of flow delay through wax valves surrounded by PDMS walls on paper microfluidics. The predried surfactant in the sample zone diffuses into the liquid sample which can therefore flow through the wax valves. The delay time is automatically regulated by the diffusion of the surfactant after sample loading. The numerical study suggested that both the elevated contact angle and the reduced porosity and pore size in the wax printed region could effectively prevent water but allow liquids with lower contact angles (, surfactant solutions) to flow through. The PDMS walls fabricated using a low-cost liquid dispenser effectively prevented the leakage of surfactant solutions. By controlling the quantity, diffusion distance, and type of the surfactant predried on the chip, the system successfully achieved a delay time ranging from 1.6 to 20 minutes. A mathematical model involving the above parameters was developed based on Fick's second law to predict the delay time. Finally, the flow-delay systems were applied in sequential mixing and distance-based detection of either glucose or alcohol. Linear ranges of 1-100 mg dL and 1-40 mg dL were achieved for glucose and alcohol, respectively. The lower limit detection (LOD) of glucose and alcohol was 1 mg dL. The LOD of glucose was only 1/11 of that detected using μPADs without flow control, indicating the advantage of controlling fluid flow. The systematic findings in this study provide critical guidelines for the development and applications of wax valves in automatic flow delay for point-of-care testing.

Automatic flow delay through passive wax valves for paper-based analytical devices.

Biosensing using liquid crystals has a tremendous potential by coupling the high degree of sensitivity of their alignment to their surroundings with clear optical feedback. Many existing set-ups use birefringence of nematic liquid crystals, which severely limits straightforward and frugal implementation into a sensing platform due to the sophisticated optical set-ups required. In this work, we instead utilize chiral nematic liquid crystal microdroplets, which show strongly reflected structural color, as sensing platforms for surface active agents. We systematically quantify the optical response of closely related biological amphiphiles and find unique optical signatures for each species. We detect signatures across a wide range of concentrations (from micromolar to millimolar), with fast response times (from seconds to minutes). The striking optical response is a function of the adsorption of surfactants in a nonhomogeneous manner and the topology of the chiral nematic liquid crystal orientation at the interface requiring a scattering, multidomain structure. We show that the surface interactions, in particular, the surface packing density, to be a function of both headgroup and tail and thus unique to each surfactant species. We show lab-on-a-chip capability of our method by drying droplets in high-density two-dimensional arrays and simply hydrating the chip to detect dissolved analytes. Finally, we show proof-of-principle  biosensing in the healthy as well as inflamed intestinal tracts of live zebrafish larvae, demonstrating CLC droplets show a clear optical response specifically when exposed to the gut environment rich in amphiphiles. Our unique approach shows clear potential in developing on-site detection platforms and detecting biological amphiphiles in living organisms.

Designing Biological Microsensors with Chiral Nematic Liquid Crystal Droplets.

Paper microfluidics has been extensively exploited as a powerful tool for environmental and medical detection applications. Both flow delay and compatibility with either polar or non-polar reagents are indispensable for the automation of detections requiring multiple reaction steps. This article reports the systematic studies of a 3D-printing protocol, characterization, and application of both the partially and fully penetrated polydimethylsiloxane (PDMS) barriers for flexible flow control in paper microfluidics. The physical parameters of PDMS barriers printed using a simple liquid dispenser were found related to the printing pressure, speed, diffusion time after printing, baking temperature, and PDMS viscosity. The capability of PDMS barriers to confine the flow of non-polar solvents was demonstrated using oil flow in both wax- and PDMS-surrounded channels. It was identified that the minimum width of channels to prevent leakage was 470 ± 54 μm, which was as narrow as that fabricated using stamps from lithography. Both the partially penetrated barriers (PPBs) and constriction channels were of the capability to delay flow in paper microfluidics. Additionally, an  investigation led to the further understanding that the reduction of channel cross-section resulting from PPBs was the primary reason for flow delay. Our results suggest that increasing the penetration depth of the barriers is more efficient in delaying flow than increasing the PPB length. Finally, devices with four inlet channels and 0-6 PPBs across each channel were successfully applied in flow delay for sequential fluid delivery. These results improve the understanding of the major factors, affecting the 3D PDMS barrier fabrication and the resulting flow control in paper microfluidics, providing practical implications for applications in various fields.

ArticleTotal : 2	Year
Publication title Cited by 9	2023
Publication title	2026

Article	Year
The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discovery. ACS central science\| PubMed ID: 31807684	2019
Automatic flow delay through passive wax valves for paper-based analytical devices. Lab on a chip\| PubMed ID: 34541589	2021
Designing Biological Microsensors with Chiral Nematic Liquid Crystal Droplets. ACS applied materials & interfaces\| PubMed ID: 35969154	2022
Development of Paper Microfluidics with 3D-Printed PDMS Barriers for Flow Control. ACS applied materials & interfaces\| PubMed ID: 36001301	2022

Chang Chen

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