Directed Particle Transport via Reconfigurable Fiber Networks

Mass transport limitations of particulates within conventional microanalytical systems are often cited as the root cause for low sensitivity but can be overcome by directed analyte transport, such as via biomolecular motors or gradient surfaces. An ongoing challenge is the development of materials that are passive in nature (i.e., no external power source required), but can reconfigure to perform work, such as transporting particle‐based analytes. Mimicking biology’s concepts of autonomous and reconfigurable materials systems, like the Drosera capensis leaf, reconfigurable fiber networks that effectively concentrate particulates within a localized spot that can act as a detection patch are developed. These networks, prepared by electrohydrodynamic co‐jetting, draw their reconfigurability from a bicompartmental fiber architecture. Upon exposure to neutral pH, a differential swelling of both fiber compartments gives rise to interfacial tension and ultimately results in shape reconfiguration of the fiber network. Compared to free particles, the reconfigurable fiber networks display a 57‐fold increase in analyte detectability, average transport efficiencies of 91.9 ± 2.4%, and separation selectivity between different surface properties of 95 ± 3%. The integration of biomimetic materials into microanalytical systems, exemplified in this study, offers ample opportunities to design novel and effective detection schemes that circumvent mass transport limitations.Biomimetic hydrogel fibers deposited in a structured spiderweb network via electrohydrodynamic co‐jet writing allow for precise control over the direction of their bending motion. The shape reconfigurable network exhibits high selectivity and efficiency in actively transporting particulates. Based on these results, their potential in overcoming mass transport limitations in microanalytical systems is demonstrated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/174803/1/adfm202204080-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/174803/2/adfm202204080_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/174803/3/adfm202204080.pd

Cervical Mucus Properties Stratify Risk for Preterm Birth

Background: Ascending infection from the colonized vagina to the normally sterile intrauterine cavity is a well-documented cause of preterm birth. The primary physical barrier to microbial ascension is the cervical canal, which is filled with a dense and protective mucus plug. Despite its central role in separating the vaginal from the intrauterine tract, the barrier properties of cervical mucus have not been studied in preterm birth. Methods and Findings: To study the protective function of the cervical mucus in preterm birth we performed a pilot case-control study to measure the viscoelasticity and permeability properties of mucus obtained from pregnant women at high-risk and low-risk for preterm birth. Using extensional and shear rheology we found that cervical mucus from women at high-risk for preterm birth was more extensible and forms significantly weaker gels compared to cervical mucus from women at low-risk of preterm birth. Moreover, permeability measurements using fluorescent microbeads show that high-risk mucus was more permeable compared with low-risk mucus. Conclusions: Our findings suggest that critical biophysical barrier properties of cervical mucus in women at high-risk for preterm birth are compromised compared to women with healthy pregnancy. We hypothesize that impaired barrier properties of cervical mucus could contribute to increased rates of intrauterine infection seen in women with preterm birth. We furthermore suggest that a robust association of spinnbarkeit and preterm birth could be an effectively exploited biomarker for preterm birth prediction.Massachusetts Institute of Technology. Charles E. Reed Faculty Initiative FundBurroughs Wellcome Fund (Preterm Birth Research Grant)National Science Foundation (U.S.). Graduate Research Fellowship Progra

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Delivery Strategies for Skin: Comparison of Nanoliter Jets, Needles and Topical Solutions

Drug diffusion within the skin with a needle-free micro-jet injection (NFI) device was compared with two well-established delivery methods: topical application and solid needle injection. A permanent make-up (PMU) machine, normally used for dermal pigmentation, was utilized as a solid needle injection method. For NFIs a continuous wave (CW) laser diode was used to create a bubble inside a microfluidic device containing a light absorbing solution. Each method delivered two different solutions into ex vivo porcine skin. The first solution consisted of a red dye (direct red 81) and rhodamine B in water. The second solution was direct red 81 and rhodamine B in water and glycerol. We measured the diffusion depth, width and surface area of the solutions in all the injected skin samples. The NFI has a higher vertical dispersion velocity of 3 × 10 5μm/s compared to topical (0.1 μm/s) and needle injection (53 μm/s). The limitations and advantages of each method are discussed, and we conclude that the micro-jet injector represents a fast and minimally invasive injection method, while the solid needle injector causes notable tissue damage. In contrast, the topical method had the slowest diffusion rate but causes no visible damage to the skin

Ionic‐Liquid‐Based Safe Adjuvants

Adjuvants play a critical role in the design and development of novel vaccines. Despite extensive research, only a handful of vaccine adjuvants have been approved for human use. Currently used adjuvants are mostly composed of components that are non‐native to the human body, such as aluminum salt, bacterial lipids, or foreign genomic material. Here, a new ionic‐liquid‐based adjuvant is explored, synthesized using two metabolites of the body, choline and lactic acid (ChoLa). ChoLa distributes the antigen efficiently upon injection, maintains antigen integrity, enhances immune infiltration at the injection site, and leads to a potent immune response against the antigen. Thus, it can serve as a promising safe adjuvant platform that can help to protect against pandemics and future infectious threats.Despite extensive research, only a handful of vaccine adjuvants, non‐native to the human body, have been approved. A new adjuvant based on ionic liquids is demonstrated, which combines two metabolites of the body, choline and lactic acid (ChoLa). It successfully enhances immune infiltration at the injection site and leads to a potent immune response against the antigen, serving as a safe adjuvant alternative that can help protect against infections.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163573/3/adma202002990.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163573/2/adma202002990-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163573/1/adma202002990_am.pd

Characterization of Particle Translocation through Mucin Hydrogels

Biological functional entities surround themselves with selective barriers that control the passage of certain classes of macromolecules while rejecting others. A prominent example of such a selective permeability barrier is given by mucus. Mucus is a biopolymer-based hydrogel that lines all wet epithelial surfaces of the human body. It regulates the uptake of nutrients from our gastrointestinal system, adjusts itself with the menstrual cycle to control the passage of sperm, and shields the underlying cells from pathogens such as bacteria and viruses. In the case of drug delivery, the mucus barrier needs to be overcome for successful medical treatment. Despite its importance for both physiology and medical applications, the underlying principles which regulate the permeability of mucus remain enigmatic. Here, we analyze the mobility of microscopic particles in reconstituted mucin hydrogels. We show that electrostatic interactions between diffusing particles and mucin polymers regulate the permeability properties of reconstituted mucin hydrogels. As a consequence, various parameters such as particle surface charge and mucin density, and buffer conditions such as pH and ionic strength, can modulate the microscopic barrier function of the mucin hydrogel. Our findings suggest that the permeability of a biopolymer-based hydrogel such as native mucus can be tuned to a wide range of settings in different compartments of our bodies