Sensing small biomolecules in biofluids remains challenging for many optical chemosensors based on supramolecular host-guest interactions due to adverse interplays with salts, proteins, and other biofluid components. Instead of following... more
Sensing small biomolecules in biofluids remains challenging for many optical chemosensors based on supramolecular host-guest interactions due to adverse interplays with salts, proteins, and other biofluid components. Instead of following the established strategy of developing alternative synthetic binders with improved affinities and selectivity, we report a molecular engineering approach that addresses this biofluid challenge. Here we introduce a cucurbit[8]uril-based rotaxane chemosensor feasible for sensing the health-relevant biomarker tryptophan at physiologically relevant concentrations, even in protein- and lipid-containing human blood serum and urine. Moreover, this chemosensor enables emission-based high-throughput screening in a microwell plate format and can be used for label-free enzymatic reaction monitoring and chirality sensing. Printed sensor chips with surface-immobilized rotaxane-microarrays are used for fluorescence microscopy imaging of tryptophan. Our system ove...
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Biomedical applications such as cell screening or cell–cell interaction studies require placement and adhesion of cells on surfaces with controlled numbers and location. In particular, single-cell arraying and positioning has come into... more
Biomedical applications such as cell screening or cell–cell interaction studies require placement and adhesion of cells on surfaces with controlled numbers and location. In particular, single-cell arraying and positioning has come into focus as a basis of such applications. An ideal substrate would combine biocompatibility with favorable attributes such as pattern stability and easy processing. Here, we present a simple yet effective approach to single-cell arraying based on a graphene oxide (GO) surface carrying protein (fibronectin) microarrays to define cell adhesion points. These capture NIH-3T3 cells, resulting in cell arrays, which are benchmarked against analogous arrays on silanized glass samples. We reveal significant improvement in cell-capture performance by the GO coating with regards to overall cell adhesion and single-cell feature occupancy. This overall improvement of cell-arraying combined with retained transparency of substrate for microscopy and good biocompatibili...
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The aim of this study is to understand the photoresponse of a Ruthenium-complex/graphene heterostructure. Early work demonstrated that light detection by graphene field effect devices was enhanced by dropcasting Ruthenium Complex... more
The aim of this study is to understand the photoresponse of a Ruthenium-complex/graphene heterostructure. Early work demonstrated that light detection by graphene field effect devices was enhanced by dropcasting Ruthenium Complex molecules. Here we proposed to fabricate a new class of devices where the Ruthenium-complex molecules are embedded between two layer of CVD monolayer graphene
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Research Interests: Materials Science, Technology, Click chemistry, Biosensor, Epoxy, and 4 moreStreptavidin, XPS, Biomolecule, and DDC
Research Interests: Physics, Materials Science, Nanoelectronics, Catalysis, Nanotechnology, and 6 moreAFM, TEM, Carbon Nanofiber, XPS, DDC, and Lambda
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Microchannel cantilever spotting is combined with a copper-free click chemistry ligation to achieve the patterning of nanocrystalline diamond films.
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Dip-pen nanolithography (DPN) and Polymer pen lithography (PPL) are powerful lithography techniques being able to pattern a wide range of inks. Transport and surface spreading depend on the ink physicochemical properties, defining its... more
Dip-pen nanolithography (DPN) and Polymer pen lithography (PPL) are powerful lithography techniques being able to pattern a wide range of inks. Transport and surface spreading depend on the ink physicochemical properties, defining its diffusive and fluid character. Structure assembly on surface arises from a balance between the entanglement of the ink itself and the interaction with the substrate. According to the transport characteristics, different models have been proposed. In this article we review the common types of inks employed for patterning, the particular physicochemical characteristics that make them flow following different dynamics as well as the corresponding transport mechanisms and models that describe them.
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Arrays of biomimetic lipid patches for studying the binding of DNA origami structures can be tailored in size, shape, and composition with the aid of lipid-dip pen nanolithography. This approach allows for analysis of the effects of lipid... more
Arrays of biomimetic lipid patches for studying the binding of DNA origami structures can be tailored in size, shape, and composition with the aid of lipid-dip pen nanolithography. This approach allows for analysis of the effects of lipid composition with high throughput which could be applied for the targeted presentation of functional DNA origami structures on surfaces.
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Analyses of rare events occurring at extremely low frequencies in body fluids are still challenging. We established a versatile microarray-based platform able to capture single target cells from large background populations. As use case... more
Analyses of rare events occurring at extremely low frequencies in body fluids are still challenging. We established a versatile microarray-based platform able to capture single target cells from large background populations. As use case we chose the challenging application of detecting circulating tumor cells (CTCs) - about one cell in a billion normal blood cells. After incubation with an antibody cocktail, targeted cells are extracted on a microarray in a microfluidic chip. The accessibility of our platform allows for subsequent recovery of targets for further analysis. The microarray facilitates exclusion of false positive capture events by co-localization allowing for detection without fluorescent labelling. Analyzing blood samples from cancer patients with our platform reached and partly outreached gold standard performance, demonstrating feasibility for clinical application. Clinical researchers free choice of antibody cocktail without need for altered chip manufacturing or in...
Research Interests: Computer Science, Technology, Biology, Medicine, Humans, and 4 moreMicroarray, Neoplasms, DDC, and Lab on a chip Devices
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Three-dimensional printing at the micro-/nanoscale represents a new challenge in research and development to achieve direct printing down to nanometre-sized objects. Here, FluidFM, a combination of microfluidics with atomic force... more
Three-dimensional printing at the micro-/nanoscale represents a new challenge in research and development to achieve direct printing down to nanometre-sized objects. Here, FluidFM, a combination of microfluidics with atomic force microscopy, offers attractive options to fabricate hierarchical polymer structures at different scales. However, little is known about the effect of the substrate on the printed structures and the integration of (bio)functional groups into the polymer inks. In this study, we printed micro-/nanostructures on surfaces with different wetting properties, and integrated molecules with different functional groups (rhodamine as a fluorescent label and biotin as a binding tag for proteins) into the base polymer ink. The substrate wetting properties strongly affected the printing results, in that the lateral feature sizes increased with increasing substrate hydrophilicity. Overall, ink modification only caused minor changes in the stiffness of the printed structures...
Research Interests: Materials Science, Nanotechnology, Polymers, Medicine, Polymer, and 3 moreNanostructure, Wetting, and Inkwell
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Biomimetic lipid membranes on solid supports have been used in a plethora of applications, including as biosensors, in research on membrane proteins or as interfaces in cell experiments. For many of these applications, structured lipid... more
Biomimetic lipid membranes on solid supports have been used in a plethora of applications, including as biosensors, in research on membrane proteins or as interfaces in cell experiments. For many of these applications, structured lipid membranes, e.g., in the form of arrays with features of different functionality, are highly desired. The stability of these features on a given substrate during storage and in incubation steps is key, while at the same time the substrate ideally should also exhibit antifouling properties. Here, we describe the highly beneficial properties of a 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer for the stability of supported lipid membrane structures generated by dip-pen nanolithography with phospholipids (L-DPN). The MPC copolymer substrates allow for more stable and higher membrane stack structures in comparison to other hydrophilic substrates, like glass or silicon oxide surfaces. The structures remain highly stable under immersion in liquid a...
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Polymeric biointerfaces are already being used extensively in a wide set of biomedical devices and systems. The possibility of controlling cell populations on biointerfaces may be essential for connecting biological systems to synthetic... more
Polymeric biointerfaces are already being used extensively in a wide set of biomedical devices and systems. The possibility of controlling cell populations on biointerfaces may be essential for connecting biological systems to synthetic materials and for researching relevant interactions between life and matter. In this study, we present and analyze synergies between an innovative approach for surface microstructuring and a molecular nanopatterning procedure of recent development. The combined set of techniques used may be instrumental for the development of a new generation of functional polymeric biointerfaces. Eukaryotic cell cultures placed upon the biointerfaces developed, both before and after molecular patterning, help to validate the proposal and to discuss the synergies between the surface microstructuring and molecular nanopatterning techniques described in the study. Their potential role in the production of versatile polymeric biointerfaces for lab- and organ-on-a-chip b...
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The level of cancer biomarkers in cells, tissues or body fluids can be used for the prediction of the presence of cancer or can even indicate the stage of the disease. Alpha-fetoprotein (AFP) is the most commonly used biomarker for early... more
The level of cancer biomarkers in cells, tissues or body fluids can be used for the prediction of the presence of cancer or can even indicate the stage of the disease. Alpha-fetoprotein (AFP) is the most commonly used biomarker for early screening and diagnosis of hepatocellular carcinoma (HCC). Here, a combination of three techniques (click chemistry, the biotin–streptavidin–biotin sandwich strategy and the use of antigen–antibody interactions) were combined to implement a sensitive fluorescent immunosensor for AFP detection. Three types of functionalized glasses (dibenzocyclooctyne- (DBCO-), thiol- and epoxy-terminated surfaces) were biotinylated by employing the respective adequate click chemistry counterparts (biotin–thiol or biotin–azide for the first class, biotin–maleimide or biotin–DBCO for the second class and biotin–amine or biotin–thiol for the third class). The anti-AFP antibody was immobilized on the surfaces via a biotin–streptavidin–biotin sandwich technique. To evalu...
Lipid-based membranes play crucial roles in regulating the interface between cells and their external environment, the communication within cells, and cellular sensing. To study these important processes, various lipid-based artificial... more
Lipid-based membranes play crucial roles in regulating the interface between cells and their external environment, the communication within cells, and cellular sensing. To study these important processes, various lipid-based artificial membrane models have been developed in recent years and, indeed, large-area arrays of supported lipid bilayers suit the needs of many of these studies remarkably well. Here, the direct-write scanning probe lithography technique called polymer pen lithography (PPL) was used as a tool for the creation of lipid micropatterns over large areas via polymer-stamp-mediated transfer of lipid-containing inks onto glass substrates. In order to better understand and control the lipid transfer in PPL, we conducted a systematic study of the influence of dwell time (i.e., duration of contact between tip and sample), humidity, and printing pressure on the outcome of PPL with phospholipids and discuss results in comparison to the more often studied dip-pen nanolithogr...
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Different types of click chemistry reactions are proposed and used for the functionalization of surfaces and materials, and covalent attachment of organic molecules. In the present work, two different catalyst-free click approaches,... more
Different types of click chemistry reactions are proposed and used for the functionalization of surfaces and materials, and covalent attachment of organic molecules. In the present work, two different catalyst-free click approaches, namely azide-alkyne and thiol-alkyne click chemistry are studied and compared for the immobilization of microarrays of azide or thiol inks on functionalized glass surfaces. For this purpose, the surface of glass is first functionalized with dibenzocyclooctyne-acid (DBCO-acid), a cyclooctyne with a carboxyl group. Then, the DBCO-terminated surfaces are functionalized via microchannel cantilever spotting with different fluorescent and nonfluorescent azide and thiol inks. Although both routes work reliably for surface functionalization, the protein binding experiments reveal that using a thiol-alkyne route will obtain the highest surface density of molecular immobilization in such spotting approaches. The obtained achievements and results from this work can...
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For many applications in the biomedical sector (especially for cell screening assays, guidance and migration experiments), gradient patterns comprising bioactive compounds over comparably (in regard to a cell size) large areas are key.... more
For many applications in the biomedical sector (especially for cell screening assays, guidance and migration experiments), gradient patterns comprising bioactive compounds over comparably (in regard to a cell size) large areas are key. Polymer pen lithography (PPL), as an inherent highly parallel and large area technique has a great potential to serve in the fabrication of such patterns. We present strategies for the printing of functional phospholipid patterns via PPL that provide tunable feature size and feature density gradients over surface areas of several square millimeters. By controlling of the printing parameters, two transfer modes can be achieved, each providing different feature morphologies. By increasing the force applied to the elastomeric pens, which increases the tip-surface contact area and boosts the ink delivery rate, a switch between a dip-pen nanolithography (DPN) to a microcontact printing (µCP) transfer mode can be induced, which was observed for the first ti...
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Nanoporous poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) (HEMA-EDMA) is used as a 3D mesh for spotting lipid arrays. Its porous structure is an ideal matrix for lipid ink to infiltrate, resulting in higher fluorescent... more
Nanoporous poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) (HEMA-EDMA) is used as a 3D mesh for spotting lipid arrays. Its porous structure is an ideal matrix for lipid ink to infiltrate, resulting in higher fluorescent signal intensity as compared to similar arrays on strictly 2D substrates like glass. The embedded lipid arrays show high stability against washing steps, while still being accessible for protein and antibody binding. To characterize binding to polymer-embedded lipids we have applied Streptavidin as well as biologically important biotinylated androgen receptor binding onto 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(cap biotinyl) (Biotinyl Cap PE) and anti-DNP IgE recognition of 2,4-dinitrophenyl[1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[6-[(2,4-dinitrophenyl)amino]hexanoyl] (DNP)] antigen. This approach adds lipid arrays to the range of HEMA polymer applications and makes this solid substrate a very attractive platform for a variety of ...
Acute subcellular protein targeting is a powerful tool to study biological networks. However, signaling at the plasma membrane is highly dynamic, making it difficult to study in space and time. In particular, sustained local control of... more
Acute subcellular protein targeting is a powerful tool to study biological networks. However, signaling at the plasma membrane is highly dynamic, making it difficult to study in space and time. In particular, sustained local control of molecular function is challenging owing to the lateral diffusion of plasma membrane targeted molecules. Herein we present "molecular-activity painting" (MAP), a novel technology which combines photoactivatable chemically induced dimerization (pCID) with immobilized artificial receptors. The immobilization of artificial receptors by surface-immobilized antibodies blocks lateral diffusion, enabling rapid and stable…
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Multi-color patterning by polymer pen lithography (PPL) was used to fabricate covalently immobilized fluorophore and oligonucleotide arrays with up to five different components. The oligonucleotide arrays offer a virtually unlimited... more
Multi-color patterning by polymer pen lithography (PPL) was used to fabricate covalently immobilized fluorophore and oligonucleotide arrays with up to five different components. The oligonucleotide arrays offer a virtually unlimited inventory of orthogonal binding tags for self-assembly of proteins as demonstrated by use of the arrays to monitor cell-protein interactions of MCF7 cells.
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Supported phospholipid membrane patches stabilized on graphene surfaces have shown potential in sensor device functionalization, including biosensors and biocatalysis. Lipid dip-pen nanolithography (L-DPN) is a method useful in generating... more
Supported phospholipid membrane patches stabilized on graphene surfaces have shown potential in sensor device functionalization, including biosensors and biocatalysis. Lipid dip-pen nanolithography (L-DPN) is a method useful in generating supported membrane structures that maintain lipid functionality, such as exhibiting specific interactions with protein molecules. Here, we have integrated L-DPN, atomic force microscopy, and coarse-grained molecular dynamics simulation methods to characterize the molecular properties of supported lipid membranes (SLMs) on graphene and graphene oxide supports. We observed substantial differences in the topologies of the stabilized lipid structures depending on the nature of the surface (polar graphene oxide vs nonpolar graphene). Furthermore, the addition of water to SLM systems resulted in large-scale reorganization of the lipid structures, with measurable effects on lipid lateral mobility within the supported membranes. We also observed reduced li...
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Protein-repellent reactive surfaces that promote localized specific binding are highly desirable for applications in the biomedical field. Nonspecific adhesion will compromise the function of bioactive surfaces, leading to ambiguous... more
Protein-repellent reactive surfaces that promote localized specific binding are highly desirable for applications in the biomedical field. Nonspecific adhesion will compromise the function of bioactive surfaces, leading to ambiguous results of binding assays and negating the binding specificity of patterned cell-adhesive motives. Localized specific binding is often achieved by attaching a linker to the surface and the other side of the linker is used to bind specifically to a desired functional agent, as e.g. proteins, antibodies, fluorophores, depending on the function required by the application. We present a protein-repellent polymer brush enabling highly specific covalent surface immobilization of biorecognition elements by strain-promoted alkyne-azide cycloaddition click chemistry for selective protein adhesion. The protein-repellent polymer brush is functionalized by highly localized molecular binding sites in the low micron range using polymer pen lithography (PPL). Due to th...
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ABSTRACT A series of MD simulations were conducted towards the selective deposition of organic luminescent molecules 3(5)-(9-anthryl) pyrazole (ANP) and perylene onto different densely packed organosilane self-assembled monolayers (SAMs).... more
ABSTRACT A series of MD simulations were conducted towards the selective deposition of organic luminescent molecules 3(5)-(9-anthryl) pyrazole (ANP) and perylene onto different densely packed organosilane self-assembled monolayers (SAMs). Our simulations indicated that the packing density of alkyl chains on SAM may directly control the site-selective deposition of organic molecules. Additionally we propose a possible mechanism for this phenomenon, which can also explain the experimental findings of the selective deposition of organic molecules onto template structures, made of l-α-dipalmitoyl-phosphatidylcholine (DPPC) in alternating liquid expanded (LE) and liquid condensed (LC) states.
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We report that nanostructuring via dip-pen nanolithography can be used for modification of a broad range of different substrates (polystyrene, Teflon, stainless steel, glass, silicon, rubber, etc.) without the need for reconfiguring the... more
We report that nanostructuring via dip-pen nanolithography can be used for modification of a broad range of different substrates (polystyrene, Teflon, stainless steel, glass, silicon, rubber, etc.) without the need for reconfiguring the underlying printing technology. This is made possible through the use of vapor-based coatings that can be deposited on these substrates with excellent conformity, while providing functional groups for subsequent spatially directed click chemistry via dip-pen nanolithography. Pattern quality has been compared on six different substrates demonstrating that this approach indeed results in a surface modification protocol with potential use for a wide range of biotechnological applications.
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A DNA-based platform was developed to address fundamental aspects of early stages of cell signaling in living cells. By site-directed sorting of differently encoded, protein-decorated DNA origami structures on DNA microarrays, we combine... more
A DNA-based platform was developed to address fundamental aspects of early stages of cell signaling in living cells. By site-directed sorting of differently encoded, protein-decorated DNA origami structures on DNA microarrays, we combine the advantages of the bottom-up self-assembly of protein-DNA nanostructures and top-down micropatterning of solid surfaces to create multiscale origami structures as interface for cells (MOSAIC). In a proof-of-principle, we use this technology to analyze the activation of epidermal growth factor (EGF) receptors in living MCF7 cells using DNA origami structures decorated on their surface with distinctive nanoscale arrangements of EGF ligand entities. MOSAIC holds the potential to present to adhered cells well-defined arrangements of ligands with full control over their number, stoichiometry, and precise nanoscale orientation. It therefore promises novel applications in the life sciences, which cannot be tackled by conventional technologies.