Michael Hirtz

Karlsruhe Institute of Technology | KIT · Institute of Nanotechnology

Surface‐bound microarrays of multiple oligo‐ and macromolecules (e.g., peptides, DNA) offer versatile options in biomedical applications like drug screening, DNA analysis, or medical diagnostics. Combinatorial syntheses of these molecules in situ can save significant resources in regard to processing time and material use. Furthermore, high feature...

The capture of circulating tumor cells (CTCs) is still a challenging application for microfluidic chips, as these cells are rare and hidden in a huge background of blood cells. Here, different microfluidic ceiling designs in regard to their capture efficiency for CTCs in model experiments and more realistic conditions of blood samples spiked with a...

Classical microcontact printing and polymer pen lithography (PPL) involve ink transfer to substrates using solid elastomeric stamps. Ink depletion thus limits the number of successive stamping steps without reinking. Porous stamps developed to overcome this limitation are used only for manual proof-of-principle experiments. Here, porous composite s...

Extracellular vesicles (EVs) contain various bioactive molecules such as DNA, RNA, and proteins, and play a key role in the regulation of cancer progression. Furthermore, cancer-associated EVs carry specific biomarkers and can be used in liquid biopsy for cancer detection. However, it is still technically challenging and time consuming to detect or...

Two‐photon lithography has revolutionized multi‐photon 3D laser printing, enabling precise fabrication of micro‐ and nanoscale structures. Despite many advancements, challenges still persist, particularly in biofunctionalization of 3D microstructures. This study introduces a novel approach combining two‐photon lithography with scanning probe lithog...

The characterization of phospholipid membrane permeability for small molecules is crucial for many applications in drug discovery and biomedical research in general. Here, chemosensor‐laden vesicles offer an attractive platform for permeability assays. In this work, the stability of immobilized chemosensor‐filled vesicles is explored on anti‐foulin...

The nanoscale arrangement of ligands can have a major effect on the activation of membrane receptor proteins and thus cellular communication mechanisms. Here we report on the technological development and use of tailored DNA origami-based molecular rulers to fabricate “Multiscale Origami Structures As Interface for Cells” (MOSAIC), to enable the sy...

Polyoxometalates (POM) are anionic oxoclusters of early transition metals that are of great interest for a variety of applications, including the development of sensors and catalysts. A crucial step in the use of POM in functional materials is the production of composites that can be further processed into complex materials, e.g. by printing on dif...

The field of bioelectronics with the aim to contact cells, cell clusters, biological tissues and organoids has become a vast enterprise. Currently, it is mainly relying on classical micro‐ and nanofabrication methods to build devices and systems. Very recently the field is highly pushed by the development of novel printable organic, inorganic and b...

Nanoglasses have attracted considerable interest among material scientists due to their novel and surprising properties. However, there is still a significant gap in understanding how nanoglasses interact with biomaterials and their effects on living cells. Previous cell studies have reported indications of possible proliferation effects, but a com...

Lipid Ink Spreading Inhibition In article number 2205590, Eider Berganza, Michael Hirtz, and co‐workers utilize dip‐pen nanolithography to print lipid patches layer‐by‐layer forming 3D structures on a surface coated with serum albumin stabilizing the structures. The lipid molecules transfer from the probe to the substrate through a water meniscus....

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, w...

Hybridization of surface‐bound DNA with complementary strands is the basis of many biotechnological applications. Herein, the structure of interfacial coatings between substrate and bound DNA is a crucial element for hybridization behavior. Herein, three reactive surfaces for constructing DNA‐sensing platforms, namely, plain gold films on silicon,...

While patterning 2D metallic nanostructures are well established through different techniques, 3D printing still constitutes a major bottleneck on the way to device miniaturization. In this work a fluid phase phospholipid ink is used as a building block for structuring with dip‐pen nanolithography. Following a bioinspired approach that relies on in...

Liquid Metal Electronics In article number 2202987, Michael Hirtz and co‐workers take a close look at gold/liquid metal contacts as they appear, e.g., in flexible electronics. By correlating complementary chemical and morphological characterization techniques, new details on the evolution of such contacts are revealed.

Diamond enables the construction of various (bio)sensors, including those with quantum‐based detection. However, bare diamond interfaces are susceptible to unspecific adhesion of proteins and other macromolecules from biological media or complex samples. This impairs selectivity in biosensing, leads to low signal‐to‐noise ratio in fluorescence‐base...

Liquid metals (LMs) play a growing role in flexible electronics and connected applications. Here, LMs come into direct contact with metal electrodes thus allowing for corrosion and additional alloying, potentially compromising device stability. Nevertheless, comprehensive studies on the interfacial interaction of the materials are still sparse. The...

Nanomaterials-based sensors are a dire need for credible and accurate determination of pesticides in water and food samples as a monitoring tool. Herein, electrocatalysts of Pd and ZnO NPs supported on a highly porous framework of activated carbons (APC) were prepared for efficient electrochemical detection of carbaryl trace. First, activated potat...

Nanomaterials-based sensors are direly needed as a monitoring tool for the credible and accurate determination of pesticides in water and food samples. Herein, electrocatalysts of Pd and ZnO nanoparticles (NPs) supported on a highly porous framework of activated carbons (APC) were prepared for efficient electrochemical detection of carbaryl trace....

Antifouling Polymer Brushes In article number 2102325, Bingquan Yang, Michael Hirtz, and co-workers investigate the efficiency of cyclooctyne click chemistry based patterned immobilization of functional compounds on azide-bearing diblock polymer brushes. Microchannel cantilever spotting (μCS) enables spotting of microarrays on the antifouling brush...

Platelets are cell fragments from megakaryocytes devoid of the cell nucleus. They are highly sensitive and easily activated by nonphysiological surfaces. Activated platelets have an intrinsic mechanism to release various proteins that participate in multiple pathways, initiating the platelet activation cascade. Surface-induced platelet activation i...

Strain‐promoted alkyne‐azide cycloaddition (SPAAC) has become an indispensable tool in bioorthogonal conjugation and surface immobilization. While numerous studies have focused on enhancing the reactivity of cyclooctynes, a facile method to evaluate the binding efficiency for cyclooctyne‐azide‐based immobilization without any sophisticated faciliti...

We have conceptualized and demonstrated an approach based on the combination of hydrophobicity, a substrate‐independent dip coating as porous material with double residual chemical reactivities for implementing multiplexed, miniaturized and unclonable bulk‐infused patterns of different fluorophores following distinct reaction pathways. The embedded...

Patterning double‐reactive porous coatings: A substrate‐independent porous dip coating with dual chemical reactivity enables multiplexed bulk‐infused and unclonable micropatterns of fluorophores attaching by distinct reaction pathways. The hydrophobicity of the coating restricts spreading of aqueous inks and enables miniaturization of patterns with...

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...

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...

Despite excelling in simple solvent mixtures, almost all known supramolecular chemosensors cannot be applied in real biofluids due to their adverse interactions with salts, proteins, and other biomolecules. Instead of following the established strategy of searching for alternative synthetic binders with improved affinity and selectivity parameters,...

Microstructuring, in particular, the additive functionalization of surfaces with, e.g., conductive or bioactive materials plays a crucial role in many applications in sensing or printed electronics. Mostly, the lithography steps are made prior to assembling functionalized surfaces into the desired places of use within a bigger device as a microflui...

The creation of biologically inspired artificial membranes on substrates with custom size and in close proximity to each other not only provides a platform to study biological processes in a simplified manner, but they also constitute building blocks for chemical or biological sensors integrated in microfluidic devices. Scanning probe lithography t...

A versatile liquid metal (LM) printing process enabling the fabrication of various fully printed devices such as intra‐ and interconnect wires, resistors, diodes, transistors, and basic circuit elements such as inverters which are process compatible with other digital printing and thin film structuring methods for integration is presented. For this...

The curvature of lipid membranes plays a key role in many relevant biological processes such as membrane trafficking, vesicular budding and host-virus interactions. In vitro studies on the membrane curvature of simplified biomimetic models in the nanometer range are challenging, due to their complicated nanofabrication processes. In this work, we p...

Immobilization of functional molecules in ordered microarrays has vast importance for many applications in sensing and diagnostics. Here, the immobilization of small molecule compounds and protein in microchannel cantilever spotting (μCS) on epoxy-terminated glass surfaces is studied via ring-opening of epoxides by thiol, amine, and azide, with the...

Immobilization of functional molecules in ordered microarrays has vast importance for many applications in sensing and diagnostics. Here, the immobilization of small molecule compounds and protein in microchannel cantilever spotting (μCS) on epoxy-terminated glass surfaces is studied via ring-opening of epoxides by thiol, amine, and azide, with the...

The patterned immobilization of chemosensors into nano/microarrays has often boosted utilization in diagnostics and environmental sensing applications. While this is a standard approach for biosensors, e.g., with antibodies, other proteins, and DNA, arraying is not yet adopted widely for supramolecular chemosensors which are still predominantly use...

Macrophages will play an important role in future diagnostics and immunotherapies of cancer. However, this demands to selectively capture and sort different subpopulations, which remains a challenge due to their innate ability to bind to a wide range of interfaces indiscriminately. The main obstacle here is the lack of interfaces combining sufficie...

New functional initiators for the cationic ring‐opening polymerization of 2‐alkyl‐2‐oxazolines are described to introduce a thiol moiety at the α terminus. Both tosylate and nosylate initiators carrying a thioacetate group are obtained in multigram scale, from commercial reagents in two steps, including a phototriggered thiol–ene radical addition....

Carbon nanofibers (CNFs), in particular branched ones, raise high interest because of their potential for nanoelectronics, catalyst presentation and applicability as dry adhesives. Here, we present a facile method based on an open ethanol flame in a microchannel for the controlled growth of coiled lambda-shaped carbon nanofibers (cλCNFs). The cλCNF...

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...

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 analyz...

Design of Nepenthes Pitcher inspired slippery liquid infused porous surface (SLIPS) appeared as an important avenue for various potential and practically relevant applications. In general, hydrophobic baselayers were infused with selected liquid lubricants for developing chemically inert SLIPS. Here, in this current study, an inherently hydrophilic...

Anti-counterfeiting measures are becoming of ever increasing importance for our society, e.g. for securing the authen-ticity of and the proof of origin for medical drugs. Here, an arms race of counterfeiters and valid manufacturers is tak-ing place, resulting in the need of hard to forge, yet easy to read-out marks. Anti-counterfeiting measures bas...

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 chemis...

The "International Research Experience for Students (IRES)" at Doane University (DU) located in Crete, Nebraska, exposed undergraduate science, technology, engineering, and mathematics (STEM) students to international research at the Karlsruhe Institute of Technology (KIT) in Germany. The international collaboration team included three undergraduat...

It is an active research field to develop novel strategies for sensitive and specific detection of protein biomarkers. Here we report an ultrasensitive biosensor to detect PTK7, an important protein biomarker on the cell surface, by aptamer conformation cooperated enzyme-assisted SERS (ACCESS) technology. Our approach features a synergistic combina...

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 sui...

Dip‐pen nanolithography (DPN) is a unique nanofabrication tool that can directly write a variety of molecular patterns on a surface with high resolution and excellent registration. Over the past 20 years, DPN has experienced a tremendous evolution in terms of applicable inks, a remarkable improvement in fabrication throughput, and the development o...

We established a versatile microarray‐based platform that is able to capture single target cell from large background populations. To show the efficacy of the device, we consider the challenging application of detecting circulating tumor cells (CTCs) – where the target cell appears in a concentration of about one cell in a billion. The cells were i...

In article number 1803944, Michael Hirtz, Hendrik Holscher, and co‐workers report on the controlled growth of carbon nanofibers (CNFs) in ∧‐ or λ‐type shape in a facile open ethanol flame process. The location and number of CNFs can be precisely controlled down to a single CNF via scanning probe lithography delivered catalytic salt features. An emp...

The locally defined growth of carbon nanofibers with lambda shape in an open flame process is demonstrated. Via the growth time, the geometry of the structures can be tailored to a Λ‐ or λ‐type shape. Microchannel cantilever spotting and dip‐pen nanolithography are utilized for the deposition of catalytic salt NiCl2 · 6H2O for locally controlled gr...

Two quick and efficient, metal catalyst free conjugation routes for the covalent attachment of functional compounds to functionalized surfaces by scanning probe lithography methods are compared in the presented work. The studied methods are thiol‐yne coupling (TYC) and thiol‐ene Michael addition (TEMA). First, the surface of hydroxyl‐terminated gla...

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 se...

People all around the world carve their initials into trees as a symbol of eternal love. But those carvings are about 1 million times larger than the paintings that were made in living cells by Y.-W. Wu, L. Dehmelt, and co-workers in their Communication http://doi.org/10.1002/anie.201611432. Although these cell paintings were not made for eternity,...

Menschen auf der ganzen Welt schnitzen ihre Initialen in Bäume als Zeichen ewiger Liebe. Diese Schnitzereien sind eine Million Mal größer als die Malereien in lebenden Zellen, die Y.-W. Wu, L. Dehmelt und Mitarbeiter in ihrer Zuschrift (http://doi.org/10.1002/ange.201611432) vorstellen. Und auch wenn diese Zellmalereien nicht für die Ewigkeit sind,...

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 h...

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...

Die akute subzelluläre Rekrutierung von Proteinen ist eine leistungsfähige Methode zur Untersuchung biologischer Netzwerke. Hoch-dynamische Signalprozesse an der Plasmamembran können bisher jedoch nur bedingt räumlich und zeitlich untersucht werden. Insbesondere durch laterale Diffusion an der Plasmamembran ist eine anhaltende lokale Steuerung mole...

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...