Material-Independent Surface Chemistry beyond Polydopamine Coating.

Various methods have been developed in surface chemistry to control interface properties of a solid material. A selection rule among surface chemistries is compatibility between a surface functionalization tool and a target material. For example, alkanethiol deposition on noble metal surfaces, widely known as the formation of a self-assembled monolayer (SAM), cannot be performed on oxide material surfaces. One must choose organosilane molecules to functionalize oxide surfaces. Thus, the surface chemistry strictly depends on the properties of the surface. Polydopamine coating is now generally accepted as the first toolbox for functionalization of virtually any material surface. Layer-by-layer (LbL) assembly is a widely used method to modify properties of versatile surfaces, including organic materials, metal oxides, and noble metals, along with polydopamine coating. On flat solid substrates, the two chemistries of polydopamine coating and LbL assembly provide similar levels of surface modifications. However, there are additional distinct features in polydopamine. First, polydopamine coating is effective for two- or three-dimensional porous materials such as metal-organic frameworks (MOFs), synthetic polyolefin membranes, and others because small-sized dopamine (MW = 153.18 u) and its oxidized oligomers are readily attached onto narrow-spaced surfaces without exhibiting steric hindrance. In contrast, polymers used in LbL assembly are slow in diffusion because of steric hindrance due to their high molecular weight. Second, it is applicable to structurally nonflat surfaces showing special wettability such as superhydrophobicity or superoleophobicity. Third, a nonconducting, insulating polydopamine layer can be converted to be a conducting layer by pyrolysis. The product after pyrolysis is a N-doped graphene-like material that is useful for graphene or carbon nanotube-containing composites. Fourth, it is a suitable method for engineering the surface properties of various composite materials. The surface properties of participating components in composite materials can be unified by polydopamine coating with a simple one-step process. Fifth, a polydopamine layer exhibits intrinsic chemical reactivity by the presence of catecholquinone moieties and catechol radical species on surfaces. Nucleophiles such as amine and thiolate spontaneously react with the functionalized layer. Applications of polydopamine coating are exponentially growing and include cell culture/patterning, microfluidics, antimicrobial surfaces, tissue engineering, drug delivery systems, photothermal therapy, immobilization of photocatalysts, Li-ion battery membranes, Li-sulfur battery cathode materials, oil/water separation, water detoxification, organocatalysts, membrane separation technologies, carbonization, and others. In this Account, we describe various polydopamine coating methods and then introduce a number of chemical derivatives of dopamine that will open further development of material-independent surface chemistry.

Site-specific fabrication of a melanin-like pigment through spatially confined progressive assembly on an initiator-loaded template.

Melanin-like nanomaterials have emerged in surface biofunctionalization in a material-independent manner due to their versatile adhesion arising from their catechol-rich structures. However, the unique adhesive properties of these materials ironically raise difficulties in their site-specific fabrication. Here, we report a method for site-specific fabrication and patterning of melanin-like pigments, using progressive assembly on an initiator-loaded template (PAINT), different from conventional lithographical methods. In this method, the local progressive assembly could be naturally induced on the given surface pretreated with initiators mediating oxidation of the catecholic precursor, as the intermediates generated from the precursors during the progressive assembly possess sufficient intrinsic underwater adhesion for localization without diffusion into solution. The pigment fabricated by PAINT showed efficient NIR-to-heat conversion properties, which can be useful in biomedical applications such as the disinfection of medical devices and cancer therapies.

Carbohydrate-protein interaction-based detection of pathogenic bacteria using a biodegradable self-powered biosensor.

Battery-free and biodegradable sensors can detect biological elements in remote areas. The triboelectric nanogenerator (TENG) can potentially eliminate the need for a battery by simply converting the abundant vibrations from nature or human motion into electricity. A biodegradable sensor system integrated with TENG to detect commonly found disease-causing bacteria (E. coli) in the environment is showcased herein. In this system, D-mannose functionalized 3D printed polylactic acid (PLA) with the brush-painted silver electrode was used to detect E. coli by a simple carbohydrate-protein interaction mechanism. The adsorption capacity of D-mannose is generally altered by varying the concentration of E. coli resulting in changes in resistance. Thus, the presented biosensor can detect bacterial concentrations by monitoring the output current. The PLA TENG generates an output of 70 V, 800 nA, and 22 nC, respectively. In addition, tap water and unpasteurized milk samples are tested for detecting bacteria, and the output is measured at 6 µA and 5 µA, respectively. Further, the biosensor was tested for biodegradability in soil compost by maintaining constant temperature and humidity. This study not only proposes an efficient and fast method for screening E. coli but also gives important insights into the ability to degrade and long-term reliability of TENG-based sensor platforms.

Dialysis-derived urchin-like supramolecular assembly of tannic acid and paclitaxel with high porosity.

Co-crystallization of active pharmaceutical ingredients (APIs) with pharmaceutically acceptable additives has emerged as an alternative to current drug delivery systems for hydrophobic drugs, due to their high drug loading efficiency. During this process, we herein report that tannic acid (TA) can be used as an amphiphilic stabilizer for the model drug, paclitaxel (PTX), that results in the shape and morphology variations of the synthesized microstructures, depending on the synthetic environment. We observed that rapid co-precipitation of PTX and TA via dialysis in water resulted in unprecedented urchin-like supramolecular microstructures with high porosity. On the other hand, slow co-precipitation for several hours under static conditions without dialysis exhibited bundles of straight TA-coated PTX fibers without any pores. This was plausibly due to the dynamic change of both the building block concentration and the solvent composition occurring during the transition of the kinetic product to the thermodynamic product. Interestingly, the synthesized urchin-like porous structure further rapidly transformed into a spherical shape through the interaction with serum proteins by remodeling of the non-covalent interactions, which contributed to the overall therapeutic efficacy tested in vitro. Our results provide knowledge on the self-assembly behavior of the hydrophobic drug and amphiphilic stabilizer under dynamic conditions, and contribute to the development of novel strategies in designing drug formulations.

Decaffeinated green tea extract as a nature-derived antibiotic alternative: An application in antibacterial nano-thin coating on medical implants.

Plant-derived polyphenols have emerged as molecular building blocks for biomedical architectures. However, the isolation of polyphenols from other components requires labor-intensive procedures, which increases costs and often raises environmental concerns. Here, we suggest that decaffeination can be a convenient and cost-effective method for enhancing the antibacterial performance of polyphenol-rich tea extracts. As a demonstration, we compared the properties of a nano-thin coating made of decaffeinated (dGT coating) and raw green tea extract (GT coating). The dGT coating exhibited enhanced antibacterial performance with regard to bacterial killing and prevention of bacterial attachment compared with the GT coating. Moreover, the chemical reactivity of the dGT coating was further utilized for secondary modifications, which enhanced the overall antibacterial performance of the modified surface. Given its intrinsic low toxicity, we envision that the developed antibacterial coating is ready for the next steps toward application in real clinical settings.

Bio-inspired strategy for on-surface synthesis of silver nanoparticles for metal/organic hybrid nanomaterials and LDI-MS substrates.

A strategy for the on-surface synthesis of silver nanoparticles (AgNPs) on a variety of two- to three-dimensional material surfaces, utilizing polydopamine, an emerging surface modifying agent, is reported in this paper. This material-independent platform for AgNP synthesis is useful for fabricating organic/inorganic hybrid nanomaterials and for preparing substrates for laser desorption-ionization time-of-flight mass spectrometry (LDI-ToF MS).

Rapid and simple single-chamber nucleic acid detection system prepared through nature-inspired surface engineering.

Background: Nucleic acid (NA)-based diagnostics enable a rapid response to various diseases, but current techniques often require multiple labor-intensive steps, which is a major obstacle to successful translation to a clinical setting. Methods: We report on a surface-engineered single-chamber device for NA extraction and in situ amplification without sample transfer. Our system has two reaction sites: a NA extraction chamber whose surface is patterned with micropillars and a reaction chamber filled with reagents for in situ polymerase-based NA amplification. These two sites are integrated in a single microfluidic device; we applied plastic injection molding for cost-effective, mass-production of the designed device. The micropillars were chemically activated via a nature-inspired silica coating to possess a specific affinity to NA. Results: As a proof-of-concept, a colorimetric pH indicator was coupled to the on-chip analysis of NA for the rapid and convenient detection of pathogens. The NA enrichment efficiency was dependent on the lysate incubation time, as diffusion controls the NA contact with the engineered surface. We could detect down to 1×103 CFU by the naked eye within one hour of the total assay time. Conclusion: We anticipate that the surface engineering technique for NA enrichment could be easily integrated as a part of various types of microfluidic chips for rapid and convenient nucleic acid-based diagnostics.

Nature-Inspired Adhesive Catecholamines for Highly Concentrated Colorimetric Signal in Spatial Biomarker Labeling.

Colorants have been utilized for precise biomarker detection in rapid and convenient colorimetric bioassays. However, the diffusion of colorants in solution often results in poor sensitivity, which is a major obstacle to the clinical translation of current colorants. To address this issue, in the current study, a unique colorant is developed that possesses adhesiveness for concentration near the target biomarker, avoiding diffusion. In nature, the synergistic interplay between catechol and amine functional groups is thought to be key for the unique mechanism of marine mussel adhesion. In addition, polymerized catecholamines are found in nature as biopigments, that is, in melanin. The dual role of catechol/catecholamine moieties in natural organics inspire to design novel colorimetric bioassays based on an adhesive colorant. Horseradish peroxidase (HRP) is used to initiate in situ polymerization of the catecholic precursors with amine-containing additive molecules and simultaneously attach them near the HRP-labeled biomarkers. This novel catecholamine-based adhesive colorant provides an excellent quantitative (naked-eye) visible signal and it also generates superb spatial information on the biomarkers on complex surfaces (e.g., cell membranes).

Material-Selective Polydopamine Coating in Dimethyl Sulfoxide.

Polydopamine coating is known to be performed in a material-independent manner and has become a popular tool when designing a surface-functionalization strategy of a given material. Studies to improve polydopamine coatings have been reported, aiming to reduce the coating time (by transition metals, oxidants, applied voltages, or microwave irradiation), control surface roughness using catechol derivatives, and vary the ad-layer molecules formed on an underlying polydopamine layer. However, none of the techniques have changed the most important intrinsic property of polydopamine, the surface-independent coating. Currently, no method has been reported to modify this property to create a material-selective 'smart' polydopamine coating. Herein, we report a method with polydopamine to differentiate the chemistry of surfaces. We found that the polydopamine coating was largely inhibited on silicon-containing surfaces such as Si wafers and quartz crystals in a dimethyl sulfoxide (DMSO)/phosphate-buffered saline (PBS) cosolvent, while the coating properties on other materials remained mostly unchanged. Among the various interface bonding mechanisms of coordination, namely, cation-π, π-π stacking, and hydrogen-bonding interactions, the DMSO/PBS cosolvent effectively inhibits hydrogen-bond formation between catechol and SiO2, resulting in surface-selective 'smart' polydopamine coatings. The new polydopamine coating is useful for functionalizing patterned surfaces such as Au patterns on SiO2 substrates. Considering that Si wafer is the most widely used substrate, the surface-selective polydopamine coating technique described herein opens up a new direction in surface functionalization and interface chemistry.

Gold Nanoparticle-Enhanced and Roll-to-Roll Nanoimprinted LSPR Platform for Detecting Interleukin-10.

Localized surface plasmon resonance (LSPR) is a powerful platform for detecting biomolecules including proteins, nucleotides, and vesicles. Here, we report a colloidal gold (Au) nanoparticle-based assay that enhances the LSPR signal of nanoimprinted Au strips. The binding of the colloidal Au nanoparticle on the Au strip causes a red-shift of the LSPR extinction peak, enabling the detection of interleukin-10 (IL-10) cytokine. For LSPR sensor fabrication, we employed a roll-to-roll nanoimprinting process to create nanograting structures on polyethylene terephthalate (PET) film. By the angled deposition of Au on the PET film, we demonstrated a double-bent Au structure with a strong LSPR extinction peak at ~760 nm. Using the Au LSPR sensor, we developed an enzyme-linked immunosorbent assay (ELISA) protocol by forming a sandwich structure of IL-10 capture antibody/IL-10/IL-10 detection antibody. To enhance the LSPR signal, we introduced colloidal Au nanocube (AuNC) to be cross-linked with IL-10 detection antibody for immunogold assay. Using IL-10 as a model protein, we successfully achieved nanomolar sensitivity. We confirmed that the shift of the extinction peak was improved by 450% due to plasmon coupling between AuNC and Au strip. We expect that the AuNC-assisted LSPR sensor platform can be utilized as a diagnostic tool by providing convenient and fast detection of the LSPR signal.

Recent advances in melanin-like nanomaterials in biomedical applications: a mini review.

BACKGROUND: Melanins are a group of biopigments in microorganisms that generate a wide range of colorants. Due to their multifunctionality, including ultraviolet protection, radical scavenging, and photothermal conversion, in addition to their intrinsic biocompatibility, natural melanins and synthetic melanin-like nanomaterials have been suggested as novel nano-bio platforms in biomedical applications. MAIN BODY: Recent approaches in the synthesis of melanin-like nanomaterials and their biomedical applications have briefly been reviewed. Melanin-like nanomaterials have been suggested as endogenous chromophores for photoacoustic imaging and radical scavengers for the treatment of inflammatory diseases. The photothermal conversion ability of these materials under near-infrared irradiation allows hyperthermia-mediated cancer treatments, and their intrinsic fluorescence can be an indicator in biosensing applications. Furthermore, catechol-rich melanin and melanin-like nanomaterials possess a versatile affinity for various functional organic and inorganic additives, allowing the design of multifunctional hybrid nanomaterials that expand their range of applications in bioimaging, therapy, theranostics, and biosensing. CONCLUSION: Melanin-like natural and synthetic nanomaterials have emerged; however, the under-elucidated chemical structures of these materials are still a major obstacle to the construction of novel nanomaterials through bottom-up approaches and tuning the material properties at the molecular level. Further advancements in melanin-based medical applications can be achieved with the incorporation of next-generation chemical and molecular analytical tools.

Point-of-care cervical cancer screening using deep learning-based microholography.

Most deaths (80%) from cervical cancer occur in regions lacking adequate screening infrastructures or ready access to them. In contrast, most developed countries now embrace human papillomavirus (HPV) analyses as standalone screening; this transition threatens to further widen the resource gap. Methods: We describe the development of a DNA-focused digital microholography platform for point-of-care HPV screening, with automated readouts driven by customized deep-learning algorithms. In the presence of high-risk HPV 16 or 18 DNA, microbeads were designed to bind the DNA targets and form microbead dimers. The resulting holographic signature of the microbeads was recorded and analyzed. Results: The HPV DNA assay showed excellent sensitivity (down to a single cell) and specificity (100% concordance) in detecting HPV 16 and 18 DNA from cell lines. Our deep learning approach was 120-folder faster than the traditional reconstruction method and completed the analysis in < 2 min using a single CPU. In a blinded clinical study using patient cervical brushings, we successfully benchmarked our platform's performance to an FDA-approved HPV assay. Conclusions: Reliable and decentralized HPV testing will facilitate cataloguing the high-risk HPV landscape in underserved populations, revealing HPV coverage gaps in existing vaccination strategies and informing future iterations.

Progressive fuzzy cation-π assembly of biological catecholamines.

Biological functions depend on biomolecular assembly processes. Assemblies of lipid bilayers, actins, microtubules, or chromosomes are indispensable for cellular functions. These hierarchical assembly processes are reasonably predictable by understanding chemical structures of the defined building blocks and their interactions. However, biopigment assembly is rather fuzzy and unpredictable because a series of covalently coupled intermediates from catecholamine oxidation pathways progressively form a higher-level hierarchy. This study reports a different yet unexplored type of assembly process named "cation-π progressive assembly." We demonstrated for the first time that the cation-π is the primary mechanism for intermolecular assembly in dopamine-melanin biopigment. We also found that the self-assembled products physically grow and chemically gain new functions "progressively" over time in which cation-π plays important roles. The progressive assembly explains how biological systems produce wide spectra of pigment colors and broad wavelength absorption through energy-efficient processes. Furthermore, we also demonstrate surface-independent wettability control using cation-π progressive assembly.

Analyses of Intravesicular Exosomal Proteins Using a Nano-Plasmonic System.

Extracellular vesicles (EVs), including exosomes, are nanoscale membrane particles shed from cells and contain cellular proteins whose makeup could inform cancer diagnosis and treatment. Most analyses have focused on surface proteins while analysis of intravesicular proteins has been more challenging. Herein, we report an EV screening assay for both intravesicular and transmembrane proteins using a nanoplasmonic sensor. Termed iNPS (intravesicular nanoplasmonic system), this platform used nanohole-based surface plasmon resonance (SPR) for molecular detection. Specifically, we i) established a unified assay protocol to detect intravesicular as well as transmembrane proteins; and ii) engineered plasmonic substrates to enhance detection sensitivity. The resulting iNPS enabled sensitive (0.5 µL sample per marker) and high-throughput (a 10 × 10 array) detection for EV proteins. When applied to monitor EVs from drug-treated cancer cells, the iNPS assay revealed drug-dependent unique EV protein signatures. We envision that iNPS could be a powerful tool for comprehensive molecular screening of EVs.

Design and clinical validation of a point-of-care device for the diagnosis of lymphoma via contrast-enhanced microholography and machine learning.

The identification of patients with aggressive cancer who require immediate therapy is a health challenge in low-income and middle-income countries. Limited pathology resources, high healthcare costs and large-case loads call for the development of advanced standalone diagnostics. Here, we report and validate an automated, low-cost point-of-care device for the molecular diagnosis of aggressive lymphomas. The device uses contrast-enhanced microholography and a deep-learning algorithm to directly analyse percutaneously obtained fine-needle aspirates. We show the feasibility and high accuracy of the device in cells, as well as the prospective validation of the results in 40 patients clinically referred for image-guided aspiration of nodal mass lesions suspicious for lymphoma. Automated analysis of human samples with the portable device should allow for the accurate classification of patients with benign and malignant adenopathy.

Facile silicification of plastic surface for bioassays.

We herein report a biomimetic technique to modify plastic substrates for bioassays. The method first places a polydopamine adhesion layer to plastic surface, and then grows conformal silica coating. As proof of principle, we coated plastic microbeads to construct a disposable filter for point-of-care nucleic acid extraction.

In vitro and in vivo analysis of visible light crosslinkable gelatin methacryloyl (GelMA) hydrogels.

Photocrosslinkable materials have been frequently used for constructing soft and biomimetic hydrogels for tissue engineering. Although ultraviolet (UV) light is commonly used for photocrosslinking such materials, its use has been associated with several biosafety concerns such as DNA damage, accelerated aging of tissues, and cancer. Here we report an injectable visible light crosslinked gelatin-based hydrogel for myocardium regeneration. Mechanical characterization revealed that the compressive moduli of the engineered hydrogels could be tuned in the range of 5-56 kPa by changing the concentrations of the initiator, co-initiator and co-monomer in the precursor formulation. In addition, the average pore sizes (26-103 µm) and swelling ratios (7-13%) were also shown to be tunable by varying the hydrogel formulation. In vitro studies showed that visible light crosslinked GelMA hydrogels supported the growth and function of primary cardiomyocytes (CMs). In addition, the engineered materials were shown to be biocompatible in vivo, and could be successfully delivered to the heart after myocardial infarction in an animal model to promote tissue healing. The developed visible light crosslinked hydrogel could be used for the repair of various soft tissues such as the myocardium and for the treatment of cardiovascular diseases with enhanced therapeutic functionality.

Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy.

Pancreatic ductal adenocarcinoma (PDAC) is usually detected late in the disease process. Clinical workup through imaging and tissue biopsies is often complex and expensive due to a paucity of reliable biomarkers. We used an advanced multiplexed plasmonic assay to analyze circulating tumor-derived extracellular vesicles (tEVs) in more than 100 clinical populations. Using EV-based protein marker profiling, we identified a signature of five markers (PDACEV signature) for PDAC detection. In our prospective cohort, the accuracy for the PDACEV signature was 84% [95% confidence interval (CI), 69 to 93%] but only 63 to 72% for single-marker screening. One of the best markers, GPC1 alone, had a sensitivity of 82% (CI, 60 to 95%) and a specificity of 52% (CI, 30 to 74%), whereas the PDACEV signature showed a sensitivity of 86% (CI, 65 to 97%) and a specificity of 81% (CI, 58 to 95%). The PDACEV signature of tEVs offered higher sensitivity, specificity, and accuracy than the existing serum marker (CA 19-9) or single-tEV marker analyses. This approach should improve the diagnosis of pancreatic cancer.

TAPE: A Biodegradable Hemostatic Glue Inspired by a Ubiquitous Compound in Plants for Surgical Application.

This video describes the simplest protocol for preparing biodegradable surgical glue that has an effective hemostatic ability and greater water-resistant adhesion strength than commercial tissue adhesives. Medical adhesives have attracted great attention as potential alternative tools to sutures and staples due to their convenience in usage with minimal invasiveness. Although there are several protocols for developing tissue adhesives including those commercially available such as fibrin glues and cyanoacrylate-based materials, mostly they require a series of chemical syntheses of organic molecules, or complicated protein-purification methods, in the case of bio-driven materials (i.e., fibrin glue). Also, the development of surgical glues exhibiting high adhesive properties while maintaining biodegradability is still a challenge due to difficulties in achieving good performance in the wet environment of the body. We illustrate a new method to prepare a medical glue, known as TAPE, by the weight-based separation of a water-immiscible supramolecular aggregate formed after a physical mixing of a plant-derived, wet-resistant adhesive molecule, Tannic Acid (TA), and a well-known biopolymer, Poly(Ethylene) glycol (PEG). With our approach, TAPE shows high adhesion strength, which is 2.5-fold more than commercial fibrin glue in the presence of water. Furthermore, TAPE is biodegradable in physiological conditions and can be used as a potent hemostatic glue against tissue bleeding. We expect the widespread use of TAPE in a variety of medical settings and drug delivery applications, such as polymers for muco-adhesion, drug depots, and others.