A new surface bioconjugation strategy is presented. A polydopamine surface coating provides chemical activation on material surfaces, is resistant to hydrolysis, and offers selectivity in coupling of biomolecules via nucleophilic groups through simple pH control. Control of orientation of immobilized biomolecules may be possible using terminally modified DNA or His‐containing proteins.

A new method for creating layer‐by‐layer (LbL) assembled films on any substrate using polymers inspired by the high catechol content of mussel adhesive proteinsis presented. Catechol‐derivatized polymers permit LbL assembly on challenging substrates without prior surface preparation. Catechol groups incorporated into the LbL film induce the reduction of silver ions to metallic silver when immersedin an aqueous metal salt solution, providing antibacterial properties.

A facile approach for material-independent surface modification using norepinephrine was investigated. pH-induced oxidative polymerization of norepinephrine forms adherent films on vastly different types of material surfaces of noble metals, metal oxides, semiconductors, ceramic, shapememory alloy and synthetic polymers. Secondary biochemical functionalizations such as immobilization of proteins and growth of biodegradable polyester on the poly(norepinephrine) films was demonstrated.Performance of most advanced materials is closely connected to their surface chemical characteristics. Examples include biosensors, medical devices, catalysts, nanomaterials, drug delivery carriers, etc. [1][2][3][4][5] Widespread methods for surface modification, such as self-assembled monolayer (SAM) and organosilane chemistry, work well on particular material surfaces compatible with the specific strategy for surface conjugation, 6 but lack efficacy on broad ranges of material surfaces. Methods that require the use of organic solvents, in some cases under anhydrous conditions, represent further limitations of existing surface modification strategies. Thus, development of versatile aqueous surface modification chemistry remains an important goal.Herein, we report a facile surface modification method utilizing norepinephrine, a small catecholamine molecule. Oxidative polymerization of norepinephrine in alkaline aqueous media modified virtually all material surfaces (noble metals, metal oxides, semiconductors, ceramics, and synthetic polymers), and the modified surfaces serve as useful platforms for biomolecule-conjugation and ring-opening polymerization.Recently, we reported a material-independent surface functionalization strategy involving selfpolymerization of dopamine to form chemically active adherent films on virtually any material surfaces including noble metals, oxides, polymers, semiconductors, and ceramics. 7 The method was inspired by the high content of 3,4-dihydroxy-L-phenylalanine (DOPA) and lysine found Dopamine is considered a small molecule mimic of Mefp-5 in that it contains the catechol and primary amine functional groups found in the side chains of DOPA and Lys residues. Incubation of substrates in an alkaline dopamine solution resulted in oxidative polymerization of dopamine and formation of a heterogeneous polymer coating. 7a A variety of secondary immobilization reactions using the polydopamine coating as a base or 'primer' led to various functional coatings, including grafted polymer coatings, metal films, and self-assembled monolayers.In an effort to further increase the versatility of this strategy, we now report organic thin film formation by derivatives of dopamine, in particular catecholamines that offer chemical functionalities not present in dopamine. Importantly, we find that norepinephrine shares the material-independent coating-forming properties of dopamine, but can also support secondary derivatization of surfaces that is difficult with polydopamine coatings. Unlike polydopamine coatings,...

During the course of their lifespan, erythrocytes actively shed phospholipid-bound, microvesicles (MVs). In stored blood, the number of these erythrocyte-derived MVs have been observed to increase over time, suggesting their potential value as a quality metric for blood products. The lack of sensitive, standardized MV assays, however, poses a significant barrier to implementing MV analyses into clinical settings. Here, we report on a new nanotechnology platform capable of rapid and sensitive MV detection in packed red blood cell (pRBC) units. A filter-assisted microfluidic device was designed to enrich MVs directly from pRBC units, and label them with target-specific magnetic nanoparticles. Subsequent detection using a miniaturized nuclear magnetic resonance system enabled accurate MV quantification as well as the detection of key molecular markers (CD44, CD47, CD55). By applying the developed platform, MVs in stored blood units could also be monitored longitudinally. Our results showed that MV counts increase over time, and thus could serve as an effective metric of blood aging. Furthermore, our studies found that MVs have the capacity to generate oxidative stress and consume nitric oxide. By advancing our understanding of MV biology, we expect that the developed platform will lead to improved blood product quality and transfusion safety.

The widespread distribution of smartphones, with their integrated sensors and communication capabilities, makes them an ideal platform for point-of-care (POC) diagnosis, especially in resourcelimited settings. Molecular diagnostics, however, have been difficult to implement in smartphones. We herein report a diffractionbased approach that enables molecular and cellular diagnostics. The D3 (digital diffraction diagnosis) system uses microbeads to generate unique diffraction patterns which can be acquired by smartphones and processed by a remote server. We applied the D3 platform to screen for precancerous or cancerous cells in cervical specimens and to detect human papillomavirus (HPV) DNA. The D3 assay generated readouts within 45 min and showed excellent agreement with gold-standard pathology or HPV testing, respectively. This approach could have favorable global health applications where medical access is limited or when pathology bottlenecks challenge prompt diagnostic readouts.T he rapid dissemination of electronic communication devices such as smartphones, tablets, and wearable electronics, all with integrated sensors, creates new possibilities for inexpensive point-of-care (POC) diagnostics and care delivery. One example is detecting cancer in low-and middle-income countries where limited resources and geographical constraints often lead to missed opportunities for intervention, resulting in mortalities even with treatable cancers (1). Current efforts to control cancer thus focus on implementing population-based early screening programs; a key element for success is a cost-effective, robust diagnostic platform that can be readily deployed into POC settings (2). Whereas conventional microscopy of human samples (smears, aspirates, biopsies, blood) is the most widely used to diagnose cancer, its POC adaptation is limited by inherent drawbacks such as bulky optics, requirements for trained microscopists, and operatordependent variability.Recent advances in digital sensors and computational approaches have introduced new microscopy techniques. Digital holography, in particular, has emerged as one alternative to conventional bright-field microscopy. Following the initial description of lens-free holography by Kreuzer's group (3), various diffractionbased imaging systems have been developed (4-8). The majority of recent work, however, is based on identifying targets by their inherent morphology (e.g., blood cells, bacteria, Caenorhabditis elegans) (4, 9-14). We reasoned that it would be possible to impart molecular specificity to improve disease detection and phenotyping akin to other molecular profiling strategies (15, 16).Here we describe a digital diffraction diagnostics (D3)-a computational analysis of distinct diffraction patterns generated by microbeads that bind to biological target of interest. The strategy can detect a broad range of targets (SI Appendix, Table S1): soluble proteins, nucleic acids, or cellular proteins. To provide effective POC operation at remote sites, we adopted a client-server model:...

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Background and Aims Early reports suggest significant difficulty with enteral feeding in critically ill COVID-19 patients. This study aimed to characterize the prevalence, clinical manifestations, and outcomes of feeding intolerance in critically ill patients with COVID-19. Methods We examined 323 adult patients with COVID-19 admitted to the intensive care units (ICUs) of Massachusetts General Hospital between March 11-June 28, 2020 who received enteral nutrition. Systematic chart review determined prevalence, clinical characteristics, and hospital outcomes (ICU complications, length of stay, and mortality) of feeding intolerance. Results Feeding intolerance developed in 56% of the patients and most commonly manifested as large gastric residual volumes (83.9%), abdominal distension (67.2%), and vomiting (63.9%). Length of intubation (OR 1.05, 95% CI 1.03-1.08), ≥1 GI symptom on presentation (OR 0.76, 95% CI 0.59-0.97), and severe obesity (OR 0.29, 95% CI 0.13-0.66) were independently associated with development of feeding intolerance. Compared to feed-tolerant patients, patients with incident feeding intolerance were significantly more likely to suffer cardiac, renal, hepatic, and hematologic complications during their hospitalization. Feeding intolerance was similarly associated with poor outcomes including longer ICU stay (median [IQR] 21.5 [14-30] vs. 15 [9-22] days, P <0.001), overall hospitalization time (median [IQR] 30.5 [19-42] vs. 24 [15-35], P <0.001) and in-hospital mortality (33.9% vs. 16.1%, P <0.001). Feeding intolerance was independently associated with an increased risk of death (HR 3.32; 95% CI 1.97-5.6). Conclusions Feeding intolerance is a frequently encountered complication in critically ill COVID-19 patients in a large tertiary care experience and is associated with poor outcomes.

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