Quorum sensing (QS) is a molecular signaling modality that mediates molecular-based cell–cell communication. Prevalent in nature, QS networks provide bacteria with a method to gather information from the environment and make decisions based on the intel. With its ability to autonomously facilitate both inter- and intraspecies gene regulation, this process can be rewired to enable autonomously actuated, but molecularly programmed, genetic control. On the one hand, novel QS-based genetic circuits endow cells with smart functions that can be used in many fields of engineering, and on the other, repurposed QS circuitry promotes communication and aids in the development of synthetic microbial consortia. Furthermore, engineered QS systems can probe and intervene in interkingdom signaling between bacteria and their hosts. Lastly, QS is demonstrated to establish conversation with abiotic materials, especially by taking advantage of biological and even electronically induced assembly processes; such QS-incorporated biohybrid devices offer innovative ways to program cell behavior and biological function.

There are many strategies to actuate and control genetic circuits, including providing stimuli like exogenous chemical inducers, light, magnetic fields, and even applied voltage, that are orthogonal to metabolic activity. Their use enables actuation of gene expression for the production of small molecules and proteins in many contexts. Additionally, there are a growing number of reports wherein cocultures, consortia, or even complex microbiomes are employed for the production of biologics, taking advantage of an expanded array of biological function. Combining stimuli-responsive engineered cell populations enhances design space but increases complexity. In this work, we co-opt nature’s redox networks and electrogenetically route control signals into a consortium of microbial cells engineered to produce a model small molecule, tyrosine. In particular, we show how electronically programmed short-lived signals (i.e., hydrogen peroxide) can be transformed by one population and propagated into sustained longer-distance signals that, in turn, guide tyrosine production in a second population building on bacterial quorum sensing that coordinates their collective behavior. Two design methodologies are demonstrated. First, we use electrogenetics to transform redox signals into the quorum sensing autoinducer, AI-1, that, in turn, induces a tyrosine biosynthesis pathway transformed into a second population. Second, we use the electrogenetically stimulated AI-1 to actuate expression of ptsH, boosting the growth rate of tyrosine-producing cells, augmenting both their number and metabolic activity. In both cases, we show how signal propagation within the coculture helps to ensure tyrosine production. We suggest that this work lays a foundation for employing electrochemical stimuli and engineered cocultures for production of molecular products in biomanufacturing environments.

Process conditions established during the development and manufacture of recombinant protein therapeutics dramatically impacts their quality and clinical efficacy. Technologies that enable rapid assessment of product quality are critically important. Here, we describe the development of sensor interfaces that directly connect to electronics and enable near real-time assessment of antibody titer and N-linked galactosylation. We make use of a spatially resolved electroassembled thiolated polyethylene glycol hydrogel that enables electroactivated disulfide linkages. For titer assessment, we constructed a cysteinylated protein G that can be linked to the thiolated hydrogel allowing for robust capture and assessment of antibody concentration. For detecting galactosylation, the hydrogel is linked with thiolated sugars and their corresponding lectins, which enables antibody capture based on glycan pattern. Importantly, we demonstrate linear assessment of total antibody concentration over an industrially relevant range and the selective capture and quantification of antibodies with terminal β-galactose glycans. We also show that the interfaces can be reused after surface regeneration using a low pH buffer.Our functionalized interfaces offer advantages in their simplicity, rapid assembly, connectivity to electronics, and reusability. As they assemble directly onto electrodes that also serve as I/O registers, we envision incorporation into diagnostic platforms including those in manufacturing settings. K E Y W O R D S antibody titer, critical quality attributes, near real time monitoring, N-linked glycosylation 1 | INTRODUCTION Recombinant antibody therapeutics constitute a large segment of the biologics market as they have shown clinical and commercial success in many therapeutic areas, including cancer, respiratory and autoimmune diseases, among others (Ecker et al., 2015; Kaplon & Reichert, 2019; Nelson et al., 2010). The development process for antibody therapeutics is costly and time-intensive due to the complexities associated with optimizing host cell lines, bioreactors, and processing conditions, along with the post-synthesis product

Background: Bedside procedure services are increasingly employed within internal medicine departments to meet clinical needs and improve trainee education.Published literature on these largely comprises single-center studies; an updated systematic review is needed to synthesize available data.Purpose: This review examined published literature on the structure and function of bedside procedure services and their impact on clinical and educational outcomes (PROSPERO ID: 192466). Data Sources: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, multiple databases were searched for publications from 2000 to 2021.Study Selection, Data Extraction, and Data Synthesis: Thirteen single-center studies were identified, including 12 observational studies and 1 randomized trial. Data were synthesized in tabular and narrative format. Services were typically staffed by hospitalists or pulmonologists. At a minimum, each offered paracentesis, thoracentesis, and lumbar puncture. While there was considerable heterogeneity in service structures, these broadly fit either Model A (service performing the procedure) or Model B (service supervising the primary team). Procedure services led to increases in procedure volumes and self-efficacy among medical residents. Assessment of clinical outcomes was limited by heterogeneous definitions of complication rates and by sparse head-to-head data involving suitable comparators. Published data pointed to high success rates, low complication rates, and high patient satisfaction, with a recent study also demonstrating a decreased length of stay.Conclusions: There are relatively few published studies describing the characteristics of bedside procedure services and their impact on clinical and educational outcomes.Limited data point to considerable heterogeneity in service design, a positive impact on medical trainees, and a positive impact on patient-related outcomes.