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 isolate cancer‐associated EVs from complex biofluids (e.g., blood). Here, a novel EV‐capture strategy based on dip‐pen nanolithography generated microarrays of supported lipid membranes is presented. These arrays carry specific antibodies recognizing EV‐ and cancer‐specific surface biomarkers, enabling highly selective and efficient capture. Importantly, it is shown that the nucleic acid cargo of captured EVs is retained on the lipid array, providing the potential for downstream analysis. Finally, the feasibility of EV capture from patient sera is demonstrated. The demonstrated platform offers rapid capture, high specificity, and sensitivity, with only a small need in analyte volume and without additional purification steps. The platform is applied in context of cancer‐associated EVs, but it can easily be adapted to other diagnostic EV targets by use of corresponding antibodies.

We click an antimicrobial peptide onto a silicon substrate to protect it from enzymolysis using a polySBMA spacer.

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 used in solution systems. Here we introduce the patterned immobilization of cucurbit[n]urils (CBn) into multiplexed microarrays and elucidate their prospects for the advancement of surface-bound indicator-displacement assays to detect small molecule analytes. The microarrays were generated by microchannel cantilever spotting of functionalized CBn and subsequent self-assembly of the corresponding indicator dyes from solution. Enhanced sensitivity of surface-bound microarrays was established in demonstrations with small bioactive metabolites (spermine, amantadine, and cadaverine) compared to bulk assays. Furthermore, the integration of the CBn/indicator microarrays into microfluidic channels provides an efficient route for real-time monitoring of the sensing process, allows easier handling, and reduces need for analyte volume. The concept was further extended to differential sensing of analytes on diplex or multiplex CBn/indicator microarrays, opening up a route for multicomponent sensing of small molecule analytes in complex liquids.

The designed antimicrobial peptide has surface binding activity onto titanium, gold, polymethyl methacrylate and hydroxyapatite substrates.

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 overcomes the limitations of current supramolecular host-guest chemosensors and will foster future applications of supramolecular sensors for molecular diagnostics.

For patients with liver failure, bilirubin (BR) is one of the endogenous toxins in their blood. Although blood purification can remove the bilirubin from the body in clinics, the detoxification system needs to be improved, and the cost needs to be decreased. In the present study, we developed a recyclable model surface that can strongly remove bilirubin. We first prepared adamantane (Ad) on a model gold surface by self-assembly. Then, we integrated the β-cyclodextrin dimer (CDD) onto the surface with host−guest interactions between one of the CD cavities in the CDD and Ad. We characterized the surface with XPS, static contact angle measurements, and AFM. In addition, we employed QCM-D to characterize the preparation process as well as the detoxification of the surface. We demonstrated that this modified surface could strongly adsorb bilirubin through host−guest interactions between the CD cavities in the CDD and bilirubin and that the detoxification was improved 1.7 times (compared to the surface only with Ad). Interestingly, after characterization with QCM-D, this surface could be recycled due to the thermoresponsive property of the host−guest interaction between the CDD and Ad. After adsorbing the toxin and increasing the temperature to 45 °C, the CDD with bilirubin could be removed from the surface. Then, the refreshed surface with CDD could be prepared again at room temperature. This cycle could be repeated at least 3 times. Additionally, during each cycle, the modified surface exhibited good detoxification to bilirubin. This modified surface also showed strong resistance to plasma proteins, decreasing the adsorption of human serum albumin (HSA) and fibrinogen (Fg). An in vitro platelet adhesion assay showed that the adhesion of the platelets on the modified surface decreased and that the platelets were in an inactivated state. The hemolysis assay showed that this surface exhibited no hemolysis activity in the samples to red blood cells (RBCs). The CCK-8 assay showed that this surface had negligible cytotoxicity to L929 cells. This work has taken advantage of the host−guest self-assembly between β-CD and BR/Ad for special recognizing adsorption, as well as the thermoresponse of β-CD-Ad inclusion for recyclable application, and these results demonstrate that this technology has great potential for removing bilirubin and decreasing clinic costs.

The curvature of lipid membranes plays a key role in many relevant biological processes such as membrane trafficking, vesicular budding or host-virus interactions. In-vitro studies on membrane curvature of simplified...

As a drug carrier, polyrotaxane (PR) has been used for targeted delivery and sustained release of drugs, whereas silver sulfadiazine (SD-Ag) is an emerging antibiotic agent. PR was synthesized by the use of α-cyclodextrin (CD) and poly(ethylene glycol) (PEG), and a specific antibacterial material (PR-(SD-Ag)) was then prepared by loading SD-Ag onto PR with different mass ratios. The loading capacity and the encapsulation efficiency were 90% at a mass ratio of 1:1 of PR and SD-Ag. SD-Ag was released stably and slowly within 6 d in vitro, and its cumulative release reached more than 85%. The mechanism of PR loading SD-Ag might be that SD-Ag attached to the edge of α-CD through hydrogen bonding. PR-(SD-Ag) showed a higher light stability than SD-Ag and held excellent antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus).