Accurate medical recordkeeping is a major challenge in many low-resource settings where well-maintained centralized databases do not exist, contributing to 1.5 million vaccine-preventable deaths annually. Here, we present an approach to encode medical history on a patient using the spatial distribution of biocompatible, near-infrared quantum dots (NIR QDs) in the dermis. QDs are invisible to the naked eye yet detectable when exposed to NIR light. QDs with a copper indium selenide core and aluminum-doped zinc sulfide shell were tuned to emit in the NIR spectrum by controlling stoichiometry and shelling time. The formulation showing the greatest resistance to photobleaching after simulated sunlight exposure (5-year equivalence) through pigmented human skin was encapsulated in microparticles for use in vivo. In parallel, microneedle geometry was optimized in silico and validated ex vivo using porcine and synthetic human skin. QD-containing microparticles were then embedded in dissolvable microneedles and administered to rats with or without a vaccine. Longitudinal in vivo imaging using a smartphone adapted to detect NIR light demonstrated that microneedle-delivered QD patterns remained bright and could be accurately identified using a machine learning algorithm 9 months after application. In addition, codelivery with inactivated poliovirus vaccine produced neutralizing antibody titers above the threshold considered protective. These findings suggest that intradermal QDs can be used to reliably encode information and can be delivered with a vaccine, which may be particularly valuable in the developing world and open up new avenues for decentralized data storage and biosensing.

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The three-dimensional (3D) cultivation of intestinal cells and tissues in dynamic bioreactor systems to represent in vivo intestinal microenvironments is essential for developing regenerative medicine treatments for intestinal diseases. We have previously developed in vitro human intestinal tissue systems using a 3D porous silk scaffold system with intestinal architectures and topographical features for the adhesion, growth, and differentiation of intestinal cells under static culture conditions. In this study, we designed and fabricated a multifunctional bioreactor system that incorporates pre-epithelialized 3D silk scaffolds in a dynamic culture environment for in vitro engineering of human intestine tissues. The bioreactor system allows for control of oxygen levels in perfusion fluids (aerobic simulated intestinal fluid (SIF), microaerobic SIF, and anaerobic SIF), while ensuring control over the mechanical and chemical microenvironments present in native human intestines. The bioreactor system also enables 3D cell culture with spatial separation and cultivation of cocultured epithelial and stromal cells. Preliminary functional analysis of tissues housed in the bioreactor demonstrated that the 3D tissue constructs survived and maintained typical phenotypes of intestinal epithelium, including epithelial tight junction formation, intestinal biomarker expression, microvilli formation, and mucus secretion. The unique combination of a dynamic bioreactor and 3D intestinal constructs offers utility for engineering human intestinal tissues for the study of intestinal diseases and discovery options for new treatments.

Antibiotic resistance is a worldwide and growing clinical problem. With limited drug development in the antibacterial space, combination therapy has emerged as a promising strategy to combat multidrug‐resistant bacteria. Antibacterial combinations can improve antibiotic efficacy and suppress antibacterial resistance through independent, synergistic, or even antagonistic activities. Combination therapies are famously used to treat viral and mycobacterial infections and cancer. However, antibacterial combinations are only now emerging as a common treatment strategy for other bacterial infections owing to challenges in their discovery, development, regulatory approval, and commercial/clinical deployment. Here, we focus on discovery—where the sheer scale of combinatorial chemical spaces represents a significant challenge—and discuss how combination therapy can impact the treatment of bacterial infections. Despite these challenges, recent advancements, including new in silico methods, theoretical frameworks, and microfluidic platforms, are poised to identify the new and efficacious antibacterial combinations needed to revitalize the antibacterial drug pipeline.

Crypt-villus architecture in the small intestine is crucial for the structural integrity of the intestinal epithelium and maintenance of gut homeostasis. We utilized three-dimensional (3D) printing and inverse molding techniques to form threedimensional (3D) spongy scaffold systems that resemble the intestinal crypt-villus microarchitecture. The scaffolds consist of silk fibroin protein with curved lumens with rows of protruding villi with invaginating crypts to generate the architecture. Intestinal cell (Caco-2, HT29-MTX) attachment and growth, as well as long-term culture support were demonstrated with cell polarization and tissue barrier properties compared to two-dimensional (2D) Transwell culture controls. Further, physiologically relevant oxygen gradients were generated in the 3D system. The various advantages of this system may be ascribed to the more physiologically relevant 3D environment, offering a system for the exploration of disease pathogenesis, host−microbiome interactions, and therapeutic discovery.

The COVID-19 pandemic has demonstrated a clear need for high-throughput, multiplexed, and sensitive assays for detecting SARS-CoV-2 and other respiratory viruses as well as their emerging variants. Here, we present microfluidic CARMEN (mCARMEN), a cost-effective virus and variant detection platform that combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel (RVP) and demonstrated its diagnostic-grade performance on 533 patient specimens in an academic setting and then 166 specimens in a clinical setting. We further developed a panel to distinguish 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 106 patient specimens, with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of viral copies in samples. mCARMEN enables high-throughput surveillance of multiple viruses and variants simultaneously.