Julian Thiele

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Verified

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• Professor
• Professor at Otto-von-Guericke University Magdeburg

Cell‐like platforms are being studied intensively for their application in synthetic biology to mimic aspects of life in an artificial environment. Here, micrometer‐sized, bifunctional microgels are used as an experimental platform to investigate the interplay of cell‐free protein synthesis (CFPS) and in situ protein accumulation inside the microge...

Concentration gradients of soluble signaling molecules—morphogens—determine the cellular organization in tissue development. Morphogen‐releasing microgels have shown potential to recapitulate this principle in engineered tissue constructs, however, with limited control over the molecular cues in space and time. Inspired by the functionality of sulf...

Modern polymer‐based technical components not only have to fulfill demanding mechanical‐structural properties but need to integrate different functions to yield hybrid systems for complex operations. Typically, neither materials nor processing technologies are fully compatible with each other. The aim of the work is to combine the advantages of see...

Thermoresponsive hydrogels were 3D-printed with embedded gold nanorods (GNRs), which enable shape change through photothermal heating. GNRs were functionalized with bovine serum albumin and mixed with a photosensitizer and poly(N-isopropylacrylamide) (PNIPAAm) macromer, forming an ink for 3D printing by direct ink writing. A macromer-based approach...

The dynamic organization of tissue development is reciprocally controlled by localized gradients of morphogens emanating from distinct clusters of cells that act as signaling centers. While microgels have shown promise to recapitulate this process in engineered tissue constructs, their capacity to tailor morphogen distribution in space and time rem...

The design of multi‐component, building block‐based assemblies of polymer materials has gained tremendous interest due to the ability to combine a functional variety and materials inside one integrated object. One such type of building blocks are polymer hydrogels that assemble into so‐called supragels. To assemble such hydrogel building blocks, it...

With the rise of particle‐based material systems in life and materials sciences over the past years, high‐throughput microfluidics has gained tremendous interest as a simple fabrication method for large quantities of tailored emulsions and microparticles. Here, we present the fabrication of microfluidic systems that combine parallelized droplet for...

Polymer materials made from hierarchically assembled building blocks form a promising material class for engineering complex systems with integrated functionality for biological or electronic applications. Herein, this work utilizes an aspiration‐based process involving a hole‐bearing glass plate to align and interconnect acrylamide‐ and N‐isopropy...

Over the past two decades, microfluidics has made significant contributions to material and life sciences, particularly via the design of nano-, micro- and mesoscale materials such as nanoparticles, micelles, vesicles, emulsion droplets, and microgels. Unmatched in control over a multitude of material parameters, microfluidics has also shed light o...

Stretching individual living cells with light is a standard method to assess their mechanical properties. Yet, heat introduced by the laser light of optical stretchers may unwittingly change the mechanical properties of cells therein. To estimate the temperature induced by an optical trap, we introduce cell-sized, elastic poly(N-isopropylacrylamide...

Microtissue Engineering In article number 2105319 by Elena Stengelin, Julian Thiele, and Sebastian Seiffert, following the 3R principles of Russell and Burch (refinement, reduction, and replacement of animal experiments), microtissue‐based in vitro model systems are discussed as potential alternatives to animal experiments. Emphasis is placed on 1)...

The soft colloidal probe (SCP) assay is a highly versatile sensing principle employing micrometer-sized hydrogel particles as optomechanical transducer elements. We report the synthesis, optimization, and conjugation of SCPs with defined narrow size distribution and specifically tailored mechanical properties and functionalities for integration int...

In recent years, stimuli-responsive hydrogels have gained tremendous interest in designing complex smart 4D materials for applications ranging from biomedicine to soft electronics that can change their properties on demand over time. However, at present, a hydrogel’s response is often induced by merely a single stimulus, restricting its broader app...

With the definition of the 3R principle by Russel and Burch in 1959, the search for an adequate substitute for animal testing has become one of the most important tasks and challenges of this time, not only from an ethical, but also from a scientific, economic, and legal point of view. Microtissue‐based in vitro model systems offer a valuable appro...

Controlled electrocoalescence of droplet pairs containing fast-gelling hydrogel precursors is highlighted as a versatile method for processing reactive species into well-defined uniform microgels as well as a special type of anisotropic microgels with a tunable curvature via droplet microfluidics.

Photopolymer Formulations In article number 2100094, Julian Thiele and coworkers describe a set of newly developed hydrophilic and hydrophobic photopolymer formulations, processed by a sophisticated example of Digital Light Processing-based 3D printing to fabricate microfluidic flow cells with planar channel geometries that exhibit spatially tailor...

The fabrication of microfluidic flow cells via projection micro‐stereolithography (PμSL) has excited researchers in recent years. However, due to the inherent process properties of most commercial PμSL, microfluidic devices are fabricated in a monolithic fashion with uniform material properties across a flow cell. Yet, the large surface‐to‐volume r...

We develop resins for high-resolution additive manufacturing of flexible micromaterials via projection microstereolithography (PμSL) screening formulations made from monomer 2-phenoxyethyl acrylate, the cross-linkers Ebecryl 8413, tri(propyleneglycol) diacrylate or 1,3,5-triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione, the photoabsorber Sudan 1, and...

Droplet microfluidics—the art and science of forming droplets—has been revolutionary for high-throughput screening, directed evolution, single-cell sequencing, and material design. However, traditional fabrication techniques for microfluidic devices suffer from several disadvantages, including multistep processing, expensive facilities, and limited...

As low‐molecular‐weight hydrogelators, dipeptide hydrogel materials are suited for embedding multiple organic molecules and inorganic nanoparticles. Herein, a simple but precisely controllable method is presented that enables the fabrication of dipeptide‐based hydrogels by supramolecular assembly inside microfluidic channels. Water‐soluble quantum...

The human brain has unique features that are difficult to study in animal models, including the mechanisms underlying neurodevelopmental and psychiatric disorders. Despite recent advances in human primary brain tissue culture systems, the use of these models to elucidate cellular disease mechanisms remains limited. A major reason for this is the la...

A dipeptide hydrogel was obtained by dynamic assembly in the confined space of continuous‐flow microfluidics. Organic porphyrins and inorganic quantum dots (QDs) were integrated in the system for energy transfer, and dynamic structural control over hydrogel formation and QD integration occurred within the microchannel network (see picture). Abstra...

In the present work, microgels were utilized as a cell-free reaction environment to produce a functional malonyl-CoA synthetase (deGFP-MatB) under geometry-controlled transcription and translation. Our approach combines the straight-forward optimization of overall protein yield of an E. coli-based cell-free protein synthesis (CFPS) system based on...

The demand for tailored, micrometer-scaled biomaterials in cell biology and (cell-free) biotechnology has led to the development of tunable microgel systems based on natural polymers, such as hyaluronic acid (HA). To precisely tailor their physicochemical and mechanical properties and thus to address the need for well-defined microgel systems, in t...

Stretching and heating are everyday experiences for skin and tissue cells. They are also standard procedures to reduce the risk for injuries in physical exercise and to relieve muscle spasms in physiotherapy. Here, we ask which immediate and long-term mechanical effects of such treatments are quantitatively detectable on the level of individual liv...

Combinatorial biosynthesis has great potential for designing synthetic circuits and amplifying the production of new active compounds. Studies on multi-enzyme cascades are extremely useful for improving our knowledge on enzymatic catalysis. In particular, the elucidation of enzyme substrate promiscuity can be potentially used for bio-retrosynthetic...

“Mimicking cellular life while combining production, separation, and purification of biomolecules on a single platform is a key step towards truly applicable cell‐like biosynthesis. To achieve simultaneous synthesis and immobilization of proteins, both DNA encoding for His‐tagged proteins and Ni‐activated NTA moieties that effectively bind such pro...

The Front Cover is provided by the Thiele group at Leibniz IPF Dresden (Germany). The image shows a microgel hosting cell‐free synthesis of green fluorescent protein. Despite its open, membrane‐free nature, the multifunctional microgel is also able to trap proteins inside its polymer matrix. More information can be found in the Article by J. Thiele...

Single-stranded deoxyribonucleic acids have an enormous potential for catalysis by applying tailored sequences of nucleotides for individual reaction conditions and substrates. If such a sequence is guanine-rich, it may arrange into a three-dimensional structure called G-quadruplex and give rise to a catalytically active DNA molecule, a DNAzyme, up...

Three-dimensional (3D) printing of microfluidic devices continuously replaces conventional fabrication methods. A versatile tool for achieving microscopic feature sizes and short process times is micro-stereolithography (µSL). However, common resins for µSL lack biocompatibility and are cytotoxic. This work focuses on developing new photo-curable r...

In current cell‐free biotechnology, mimicking physicochemical aspects of cellular life while providing efficient protein synthesis, separation, and purification is a crucial step towards truly applicable artificial, yet cell‐like, biosynthesis platforms. To achieve simultaneous synthesis and immobilization of proteins in a tailor‐made environment,...

Multiphasic in vitro models with cross-scale heterogeneity in matrix properties and/or cellular composition can reflect the structural and compositional complexity of living tissues more faithfully, thereby creating new options for pathobiology and drug development studies. Herein a new class of tunable microgel-in-gel materials is reported that bu...

We introduce a novel concept for mechanosensitive hydrogel microparticles, which translate deformation into changes in fluorescence and can thus function as mechanical probes. The hydrogel particles with controlled polymer network are produced via droplet microfluidics from poly(ethylene glycol) (PEG) precursors. Förster resonance energy transfer d...

Hyaluronan (HA)-based microgels generated in a microfluidic approach, containing an artificial extracellular matrix composed of collagen and high-sulfated hyaluronan (sHA3), were incorporated into a HA/collagen-based hydrogel matrix. This significantly enhanced the retention of noncrosslinked sHA3 within the gels enabling controlled sHA3 presentati...

The fabrication of microfluidic devices with nonplanar microchannel design by micro‐stereolithography (µSL) for oil‐in‐water (O/W) and water‐in‐oil (W/O) single emulsion as well as oil‐in‐water‐in‐oil (O/W/O) and water‐in‐oil‐in‐water (W/O/W) double emulsion formation is presented. By investigating separation distance, printing direction and voxel...

Polysaccharide-based microgels have broad applications in multi-parametric cell cultures, cell-free biotechnology, and drug delivery. Multicomponent reactions like the Passerini three-component and the Ugi four-component reaction are shown in here to be versatile platforms for fabricating these polysaccharide microgels by droplet microfluidics with...

Cell mechanical measurements are gaining increasing interest in biological and biomedical studies. However, there are no standardized calibration particles available that permit the cross-comparison of different measurement techniques operating at different stresses and time-scales. Here we present the rational design, production, and comprehensive...

Cell mechanical measurements are gaining increasing interest in biological and biomedical studies. However, there are no standardized calibration particles available that permit the cross-comparison of different measurement techniques operating at different stresses and time-scales. Here we present the rational design, production, and comprehensive...

Microfluidic flow cells provide excellent control over the formation of microemulsions, which are widely applied as templates for the fabrication of hydrogel microparticles and vesicles with defined physicochemical properties. In recent years, bio-orthogonal synthesis schemes of macromolecular building blocks as well as their microfluidic processin...

Over the last two decades, droplet-based microfluidics has evolved into a versatile tool for fabricating tailored micrometer-sized hydrogel particles. Combining precise fluid handling down to femtoliter scale with diverse hydrogel precursor design, it allows for excellent control over microgel size and shape, but also functionalization and crosslin...

In droplet-based microfluidics, non-ionic, high-molecular weight surfactants are required to stabilize droplet interfaces. One of the most common structures that imparts stability as well as biocompatibility to water-in-oil droplets is a triblock copolymer surfactant composed of perfluoropolyether (PFPE) and polyethylene glycol (PEG) blocks. Howeve...

In highly crowded and viscous intracellular environments, the kinetics of complex enzymatic reactions are determined by both reaction and diffusion rates. However in vitro studies on transcription and translation often fail to take into account the density of the prokaryotic cytoplasm. Here we mimic the cellular environment, using a porous hydrogel...

We present a simple method to microfluidically align and trap 1D nanostructures from suspension at well-defined positions on a receiver substrate for the fabrication of single-nanowire field effect transistors (NW FETs). Our approach allows for subsequent contacting of deposited NWs via standard UV-lithography. We demonstrate that silicon as well a...

Droplet microfluidics is combined with bio-orthogonal thiol–ene click chemistry to fabricate micrometer-sized, monodisperse fibrinogen-containing hyaluronic acid hydrogel microbeads in a mild, radical-free procedure in the presence of human mesenchymal stem cells (hMSCs). The gel beads serve as microniches for the 3D culture of single hMSCs, contai...

Droplet-based microfluidics is increasingly used for biological applications, where the recovery of cells or particles after an experiment or assay is desirable. Here, we present an electro-demulsification chip which circumvents the use of harsh chemicals and multiple washing/centrifugation steps and offers a mild way for extracting cells and polym...

We microfluidically fabricate bio-orthogonal DNA-functionalized porous hydrogels from hyaluronic acid that are employed in in vitro transcription/translation (IVTT) of a green fluorescent protein. By co-encapsulating individual hydrogel particles and the IVTT machinery in water-in-oil microdroplets, we study protein expression in a defined reaction...

Cell culturing, whether for tissue engineering or cell biology studies, always involves placing cells in a non-natural environment and no material currently exist that can mimic the entire complexity of natural tissues and variety of cell-matrix interactions that is found in vivo. Here, we review the vast range of hydrogels, composed of natural or...

Many approaches to mimic and understand the dynamics of vesicle budding lack precise control over vesicle membrane properties or require external stimuli to induce budding. We use copolymer-loaded double-emulsion droplets to precisely control size, size distribution, composition and morphology of giant polymersomes. By tuning the copolymer concentr...

Vesicles are compartments enclosed by a thin membrane, which is made up of amphiphilic molecules arranged into ordered layers. Vesicle-like structures are Nature’s choice for encapsulating important biochemical species that enable living processes, and are increasingly important as artificial structures for the encapsulation and release of drugs, b...

A series of water-soluble macro-initiators is synthesized to avoid radical loss in microfluidic on-chip photo cross-linking of hyaluronic acid methacrylate-containing water-in-oil emulsions. Their superior performance over known photo-initiators through the generation of water-soluble radicals and excellent biocompatibility are demonstrated.

Here, we present a platform to detect cytokine (IL-2, IFN-γ, TNF-α) secretion of single, activated T-cells in droplets over time. We use a novel droplet-based microfluidic approach to encapsulate cells in monodisperse agarose droplets together with functionalized cytokine-capture beads for subsequent binding and detection of secreted cytokines from...

The flow orientation of anisotropic particles through narrow channels is of importance in many fields, ranging from the spinning and molding of fibers to the flow of cells and proteins through thin capillaries. It is commonly assumed that anisotropic particles align parallel to the flow direction. When flowing through narrowed channel sections, one...

Microgel particles are formed from aqueous-two-phase-system (ATPS) droplets in poly(dimethylsiloxane) (PDMS) microfluidic devices. The droplets consist of a dextran core and a photopolymerizable poly(ethylene glycol) diacrylate (PEGDA) shell. Upon UV exposure, the ATPS droplets undergo a shape-transformation yielding PEGDA microgel particles contai...

Like charges stabilize emulsions, whereas opposite charges break emulsions. This is the fundamental principle for many industrial and practical processes. Using micrometer-sized pH-sensitive polymeric hydrogel particles as emulsion stabilizers, we prepare emulsions that consist of oppositely charged droplets, which do not coalesce. We observe nonco...

Monodisperse microscale drops formed with microfluidic devices are useful for encapsulating cells, microgel particles, or even additional drops. These techniques are thus useful for applications ranging from high-throughput biology to monodisperse particle and capsule synthesis, which require encapsulation of such objects. However, it is challengin...

Double emulsions are valuable structures that consist of drops nested inside bigger drops; they can be formed with exquisite control through the use of droplet-based microfluidics, allowing their size, composition, and monodispersity to be tailored. However, only little control can be exerted on the morphology of double emulsions in their equilibri...

Early development drug formulation is exacerbated by increasingly poor bioavailability of potential candidates. Prevention of attrition due to formulation problems necessitates physicochemical analysis and formulation studies at a very early stage during development, where the availability of a new substance is limited to small quantities, thus imp...

We present a robust way to create multiple emulsions with controllable shell thicknesses that can vary over a wide range. We use a microfluidic device to create a coaxial jet of immiscible fluids; using a dripping instability, we break the jet into multiple emulsions. By controlling the thickness of each layer of the jet, we adjust the thicknesses...

The formation of polymersomes from copolymer-stabilized double emulsions in glasscoated, PDMS microfluidic devices is described. The device geometry enables separate injection of two organic solvents to form the shell phase of the double emulsion. This allows proper combination of the two solvents, which is essential for forming polymersomes.

We present a simple method to spatially pattern the surface properties of microfluidic devices using flow confinement. Our technique allows surface patterning with micron-scale resolution. To demonstrate its effectiveness, we use it to pattern wettability to form W/O/W and O/W/O double emulsions.

Microgel particles and capsules which consist of multiple layers can be fabricated using droplet microfluidics, but in existing methods, emulsion templating forms layers of dissimilar polarity. In this paper, we fabricate functional microgel capsules that consist of two miscible yet distinct layers. We use microfluidic devices to template micromete...

We demonstrate that microfluidic flow devices enable a rapid, continuous, well-reproducible and size-controlled preparation of unilamellar block copolymer vesicles. The PDMS-based microfluidic device consists of perpendicularly crossed channels allowing hydrodynamic flow focusing of an ethanolic block copolymer solution in a stream of water. By alt...

We describe new developments for controlled fabrication of monodisperse non‐spherical particles using droplet microfluidics. The high degree of control afforded by microfluidic technologies enables generation of single and multiple emulsion droplets. We show that these droplets can be transformed to non‐spherical particles through further simple, s...

In this study a new procedure using Synchrotron total reflection X-ray fluorescence (SR-TXRF) to characterize elemental amounts in atmospheric aerosols down to particle sizes of 0.015 um is presented. The procedure was thoroughly evaluated regarding bounce off effects and blank values. Additionally the potential of total reflection X-ray fluorescen...

The characteristics of dried residues of picodroplets of single-, two-, and three-element aqueous solutions, which qualify these as reference materials in the direct analysis of single particles, single cells, and other microscopic objects using, e.g., laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOF-MS) and mi...

Journal article