Chiral particle separation by a non-chiral micro-lattice

We conceived a model experiment for a continuous separation strategy of chiral molecules (enantiomers) without the need of any chiral selector structure or derivatization agents: Micro-particles that only differ by their chirality are shown to migrate along different directions when driven by a steady fluid flow through a square lattice of cylindrical posts. In accordance with our numerical predictions, the transport directions of the enantiomers depend very sensitively on the orientation of the lattice relatively to the fluid flow

Two-Photon 3D Laser Printing Inside Synthetic Cells

Toward the ambitious goal of manufacturing synthetic cells from the bottom up, various cellular components have already been reconstituted inside lipid vesicles. However, the deterministic positioning of these components inside the compartment has remained elusive. Here, by using two-photon 3D laser printing, 2D and 3D hydrogel architectures are manufactured with high precision and nearly arbitrary shape inside preformed giant unilamellar lipid vesicles (GUVs). The required water-soluble photoresist is brought into the GUVs by diffusion in a single mixing step. Crucially, femtosecond two-photon printing inside the compartment does not destroy the GUVs. Beyond this proof-of-principle demonstration, early functional architectures are realized. In particular, a transmembrane structure acting as a pore is 3D printed, thereby allowing for the transport of biological cargo, including DNA, into the synthetic compartment. These experiments show that two-photon 3D laser microprinting can be an important addition to the existing toolbox of synthetic biology

4D Printing at the Microscale

3D printing of adaptive and dynamic structures, also known as 4D printing, is one of the key challenges in contemporary materials science. The additional dimension refers to the ability of 3D printed structures to change their properties—for example, shape—over time in a controlled fashion as the result of external stimulation. Within the last years, significant efforts have been undertaken in the development of new responsive materials for printing at the macroscale. However, 4D printing at the microscale is still in its early stages. Thus, this progress report will focus on emerging materials for 4D printing at the microscale as well as their challenges and potential applications. Hydrogels and liquid crystalline and composite materials have been identified as the main classes of materials representing the state of the art of the growing field. For each type of material, the challenges and critical barriers in the material design and their performance in 4D microprinting are discussed. Importantly, further necessary strategies are proposed to overcome the limitations of the current approaches and move toward their application in fields such as biomedicine, microrobotics, or optics

3D Scaffolds to Study Basic Cell Biology

Mimicking the properties of the extracellular matrix is crucial for developing in vitro models of the physiological microenvironment of living cells. Among other techniques, 3D direct laser writing (DLW) has emerged as a promising technology for realizing tailored 3D scaffolds for cell biology studies. Here, results based on DLW addressing basic biological issues, e.g., cell-force measurements and selective 3D cell spreading on functionalized structures are reviewed. Continuous future progress in DLW materials engineering and innovative approaches for scaffold fabrication will enable further applications of DLW in applied biomedical research and tissue engineering

Bio‐Metamaterials for Mechano‐Regulation of Mesenchymal Stem Cells

Cell behaviors significantly depend on the elastic properties of the microenvironments, which are distinct from commonly used polymer-based substrates. Artificial elastic materials called metamaterials offer large freedom to adjust their effective elastic properties as experienced by cells, provided (i) the metamaterial unit cell is sufficiently small compared to the biological cell size and (ii) the metamaterial is sufficiently soft to deform by the active cell contraction. Thus, metamaterials targeting bio-applications (bio-metamaterials) appear as a promising path toward the mechanical control of stem cells. Herein, human mesenchymal stem cells (hMSCs) are cultured on three different types of planar periodic elastic metamaterials. To fulfill the above two key requirements, microstructured bio-metamaterials have been designed and manufactured based on a silicon elastomer-like photoresist and two-photon laser printing. In addition to the conventional morphometric and immunocytochemical analysis, the traction force that hMSCs exert on metamaterials are inferred by converting the measured displacement-vector fields into force-vector fields. The differential responses of hMSCs, both on the cellular level and the sub-cellular level, correlate with the calculated effective elastic properties of the bio-metamaterials, suggesting the potential of bio-metamaterials toward mechanical regulation of cell behaviors by the arrangement of unit cells

Imaging intensive care patients: multidisciplinary conferences as a quality improvement initiative to reduce medical error

Background: Strategies to identify imaging-related error and minimise its consequences are important in the management of critically ill patients. A new quality management (QM) initiative for radiological examinations has been implemented in an intensive care unit (ICU) setting. In regular multidisciplinary conferences (MDCs), radiologists and ICU physicians re-evaluate recent examinations. Structured bilateral feedback is provided to identify errors early. This study aims at investigating its impact on the occurrence of QM events (imaging-related errors). Standardised protocols of all MDCs from 1st of June 2018 through 31st of December 2019 were analysed with regard to categories of QM events (i.e. indication, procedure, report) and resulting consequences. Results: We analysed 241 MDCs with a total of 973 examinations. 14.0% (n = 136/973) of examinations were affected by QM events. The majority of events were report-related (76.3%, n = 106/139, e.g. misinterpreted finding), followed by procedure-related (18.0%, n = 25/139, e.g. technical issue) and indication-related events (5.8%, n = 8/139, e.g. faulty indication). The median time until identification of a QM event (time to MDC) was 2 days (interquartile range = 2). Comparing the first to the second half of the intervention period, the incidence of QM events decreased significantly from 22.9% (n = 109/476) to 6.0% (n = 30/497) (p < 0.0001). Significance of this effect was confirmed by linear regression (p < 0.0001). Conclusions: Establishing structured discussion and feedback between radiologists and intensive care physicians in the form of MDCs is associated with a statistically significant reduction in QM events. These results indicate that MDCs may be one suitable approach to timely identify imaging-related error

Postoperative Radiotherapy of Prostate Cancer: Adjuvant versus Early Salvage.

Results of three randomized clinical trials (RCTs) comparing adjuvant radiotherapy (ART) and early salvage radiotherapy (eSRT) of prostate carcinoma and a subsequent meta-analysis of the individual patient data from these RCTs were recently published. The results suggest that early eSRT is as effective and potentially less toxic than ART. Therefore, eSRT should be considered the standard of care. However, due to limitations in the RCTs, ART remains a valid treatment option in patients with the combination of high-risk features such as Gleason Score (GS) 8-10, positive surgical margins (R1) and pathological T-stage 3 or 4 (pT3/4). This article provides a critical appraisal of the RCTs and the rationale for recommendations adopted in the current national guidelines regarding patients with high-risk features after radical prostatectomy (RP): ART should be offered in case of pT3/pT4 and R1 and Gleason Score 8-10; ART can be offered in case of pT3/pT4 and R0 and Gleason Score 8-10 as well as in case of multifocal R1 (including pT2) and Gleason Score 8-10. In any case, the alternative treatment option of eSRT in case of rising PSA should be discussed with the patient

Mechanical stimulation of single cells by reversible host-guest interactions in 3D microscaffolds

Many essential cellular processes are regulated by mechanical properties of their microenvironment. Here, we introduce stimuli-responsive composite scaffolds fabricated by three-dimensional (3D) laser lithography to simultaneously stretch large numbers of single cells in tailored 3D microenvironments. The key material is a stimuli-responsive photoresist containing cross-links formed by noncovalent, directional interactions between β-cyclodextrin (host) and adamantane (guest). This allows reversible actuation under physiological conditions by application of soluble competitive guests. Cells adhering in these scaffolds build up initial traction forces of ~80 nN. After application of an equibiaxial stretch of up to 25%, cells remodel their actin cytoskeleton, double their traction forces, and equilibrate at a new dynamic set point within 30 min. When the stretch is released, traction forces gradually decrease until the initial set point is retrieved. Pharmacological inhibition or knockout of nonmuscle myosin 2A prevents these adjustments, suggesting that cellular tensional homeostasis strongly depends on functional myosin motors

Controlling the shape of 3D microstructures by temperature and light

Stimuli-responsive microstructures are critical to create adaptable systems in soft robotics and biosciences. For such applications, the materials must be compatible with aqueous environments and enable the manufacturing of three-dimensional structures. Poly(N-isopropylacrylamide) (pNIPAM) is a well-established polymer, exhibiting a substantial response to changes in temperature close to its lower critical solution temperature. To create complex actuation patterns, materials that react differently with respect to a stimulus are required. Here, we introduce functional three-dimensional hetero-microstructures based on pNIPAM. By variation of the local exposure dose in three-dimensional laser lithography, we demonstrate that the material parameters can be altered on demand in a single resist formulation. We explore this concept for sophisticated three-dimensional architectures with large-amplitude and complex responses. The experimental results are consistent with numerical calculations, able to predict the actuation response. Furthermore, a spatially controlled response is achieved by inducing a local temperature increase by two-photon absorption of focused light