The presented microrobotic platform combines together the advantages of self-folding NIR light sensitive polymer bilayers, magnetic alginate microbeads, and a 3D manipulation system, to propose a solution for targeted, on-demand drug and cell delivery. First feasibility studies are presented together with the potential of the full design.

Preparation-free and skin compliant biopotential electrodes with high recording quality enable wearables for future healthcare and the Internet of Humans. Here, super-soft and self-adhesive electrodes are presented for use on dry and hairy skin without skin preparation or attachment pressure. The electrodes show a skin-contact impedance of 50 kΩ cm at 10 Hz that is comparable to clinical standard gel electrodes and lower than existing dry electrodes. Microstructured electrodes inspired by grasshopper feet adhere repeatedly to the skin with a force of up to 0.1 N cm without further attachment even during strong movement or deformation of the skin. Skin compliance and adhesive properties of the electrodes result in reduction of noise and motion artifacts superior to other dry electrodes reaching the performance of commercial gel electrodes. The signal quality is demonstrated by recording a high-fidelity electrocardiograms of a swimmer in water. Furthermore, an electrode with soft macropillars is used to detect alpha activity in the electroencephalograms from the back of the head through dense hair. Compared to gel electrodes, the soft biopotential electrodes are nearly imperceptible to the wearer and cause no skin irritations even after hours of application. The electrodes presented here could combine unobtrusive and long-term biopotential recordings with clinical-grade signal performance.

Superparamagnetic nanoparticles and a functional, degradable polymer matrix based on poly(ethylene glycol) are combined to enable fully degradable magnetic microdevices for minimally invasive biomedical applications. A bioinspired helical microrobot platform mimicking Escherichia coli bacteria is fabricated and actuated using weak rotating magnetic fields. Locomotion based on corkscrew propulsion, targeted drug delivery, and low-degradation-product cytotoxicity are demonstrated.

Nanoparticles are currently being investigated in a number of human clinical trials. As information on how nanoparticles function in humans is difficult to obtain, animal studies that can be correlative to human behavior are needed to provide guidance for human clinical trials. Here, we report correlative studies on animals and humans for CRLX101, a 20-to 30-nm-diameter, multifunctional, polymeric nanoparticle containing camptothecin (CPT). CRLX101 is currently in phase 2 clinical trials, and human data from several of the clinical investigations are compared with results from multispecies animal studies. The pharmacokinetics of polymer-conjugated CPT (indicative of the CRLX101 nanoparticles) in mice, rats, dogs, and humans reveal that the area under the curve scales linearly with milligrams of CPT per square meter for all species. Plasma concentrations of unconjugated CPT released from CRLX101 in animals and humans are consistent with each other after accounting for differences in serum albumin binding of CPT. Urinary excretion of polymer-conjugated CPT occurs primarily within the initial 24 h after dosing in animals and humans. The urinary excretion dynamics of polymer-conjugated and unconjugated CPT appear similar between animals and humans. CRLX101 accumulates into solid tumors and releases CPT over a period of several days to give inhibition of its target in animal xenograft models of cancer and in the tumors of humans. Taken in total, the evidence provided from animal models on the CRLX101 mechanism of action suggests that the behavior of CRLX101 in animals is translatable to humans.nanomedicine | clinical translation | interspecies scaling | pharmacodynamics | Nanoparticles

Directed nanoparticle self‐organization and two‐photon polymerization are combined to enable three‐dimensional soft‐magnetic microactuators with complex shapes and shape‐independent magnetic properties. Based on the proposed approach, single and double twist‐type swimming microrobots with programmed magnetic anisotropy are demonstrated, and their swimming properties in DI‐water are characterized. The fabricated devices are actuated using weak rotating magnetic fields and are capable of performing wobble‐free corkscrew propulsion. Single twist‐type actuators possess an increase in surface area in excess of 150% over helical actuators with similar feature size without compromising the forward velocity of over one body length per second. A generic and facile combination of glycine grafting and subsequent protein immobilization exploits the actuator's increased surface area, providing for a swimming microrobotic platform with enhanced load capacity desirable for future biomedical applications. Successful surface modification is confirmed by FITC fluorescence.

There has been recent controversy as to whether platelet ␣-granules represent a single granule population or are composed of different subpopulations that serve discrete functions. To address this question, we evaluated the localization of vesicle-associated membrane proteins (VAMPs) in spread platelets to determine whether platelets actively sort a specific subpopulation of ␣-granules to the periphery during spreading. Immunofluorescence microscopy demonstrated that granules expressing VAMP-3 and VAMP-8 localized to the central granulomere of spread platelets along with the granule cargos von Willebrand factor and serotonin. In contrast, ␣-granules expressing VAMP-7 translocated to the periphery of spread platelets along with the granule cargos TIMP2 and VEFG. Time-lapse microscopy demonstrated that ␣-granules expressing VAMP-7 actively moved from the granulomere to the periphery during spreading. Platelets from a patient with gray platelet syndrome lacked ␣-granules and demonstrated only minimal spreading. Similarly, spreading was impaired in platelets obtained from Unc13d Jinx mice, which are deficient in Munc13-4 and have an exocytosis defect. These studies identify a new ␣-granule subtype expressing VAMP-7 that moves to the periphery during spreading, supporting the premise that ␣-granules are heterogeneous and demonstrating that granule exocytosis is required for platelet spreading. IntroductionPlatelets are replete with granules containing cargo that is required for platelet function in hemostasis, thrombosis, inflammation, angiogenesis, and malignancy. [1][2][3][4] Platelet granule types include ␣-granules, dense granules, and lysosomes. Of these granule types, the ␣-granule is by far the most abundant with 50 to 80 granules/ platelet, compared with 3 to 6 dense granules/platelet and 0 to 3 lysosomes/platelet. Recent studies indicate that ␣-granules may not constitute a homogenous population. There is evidence that ␣-granule subpopulations can be distinguished on the basis of morphology, 5 cargo type, 6-8 and response to agonists. 7-10 However, experiments using high resolution immunofluorescence microscopy have raised the possibility that the distribution of cargo among ␣-granules is largely stochastic and that the apparent segregation observed by standard immunofluorescence microscopy could result from segregation within granules. 11,12 Although the study of ␣-granule heterogeneity has focused primarily on the localization and release of granule cargo, granules also serve an essential role in membrane remodeling. In nucleated cells, granules provide an internal reservoir of membrane to expand and reshape the plasma membrane during cell movement, 13 membrane resealing, 14,15 neurite outgrowth, [16][17][18] and development of the phagocytotic cup in macrophages. 19,20 Different subpopulations of granules demonstrate different behaviors during membrane remodeling. Recent studies demonstrate that these different granule types can be distinguished by the vesicle-associated membrane proteins (VAMPs) that th...

Key Points Parmodulins are a new class of PAR1 inhibitors that target the cytosolic face of PAR1 to block signaling through Gαq, but not Gα12/13. Unlike vorapaxar, which causes endothelial injury, parmodulins selectively block proinflammatory, but not cytoprotective, signaling.

This paper presents a novel electrically tunable structure which can be used as a resonator for vibration-based energy harvesters. The adjustment of the resonance frequency is provided by mechanical stiffening of the structure using piezoelectric actuators. This concept can easily be stand-alone integrated to realize an autonomous, tunable harvester. The resonator was simulated using ANSYS to find the optimum operation point concerning tuning range. The scalability of this tuning concept is also investigated in this work. A phase shift control circuit was developed for very efficient autonomous closed-loop control of the resonance frequency. Prototypes of the resonators were fabricated and measured with and without the control circuit. The tuning voltage can be kept as low as ±5 V leading to a measured resonance shift of ±15% for the larger resonator (40 mm) and around ±8% for the smaller resonator (27 mm). This tuning range can be simply enhanced by increasing the tuning voltage.