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Summary Extracellular vesicles (EVs) harbor a rich glycome—diverse sugar modifications—that mediates and reflects disease progression. Despite its clinical potential, the analysis of EV glycans remains challenging due to limitations of current glycomics technologies. Here, we develop a dedicated analytical platform to directly profile EV glycans in native biofluids. Termed integrated magnetic analysis of glycans in extracellular vesicles (iMAGE), the platform utilizes rationally designed polycore magnetic nanoparticles to transduce EV-bound glycans, but not that of free-floating glycoproteins, into magnetic signals; the resultant signals are readily quantified through a built-in magnetoresistance sensor. The iMAGE assay is thus fast (

The controlled assembly of nanomaterials into desired architectures presents many opportunities; however, current preparations lack spatial precision and versatility in developing complex nano-architectures. Inspired by the amphiphilic nature of surfactants, we develop a facile approach to guide nanomaterial integration – spatial organization and distribution – in metal-organic frameworks (MOFs). Named surfactant tunable spatial architecture (STAR), the technology leverages the varied interactions of surfactants with nanoparticles and MOF constituents, respectively, to direct nanoparticle arrangement while molding the growing framework. By surfactant matching, the approach achieves not only tunable and precise integration of diverse nanomaterials in different MOF structures, but also fast and aqueous synthesis, in solution and on solid substrates. Employing the approach, we develop a dual-probe STAR that comprises peripheral working probes and central reference probes to achieve differential responsiveness to biomarkers. When applied for the direct profiling of clinical ascites, STAR reveals glycosylation signatures of extracellular vesicles and differentiates cancer patient prognosis., Current methods for controlled assembly of nanomaterials into desired architectures often lack the precision and versatility to develop complex architectures. Here the authors report STAR, surfactant tunable spatial architecture, to guide nanomaterial integration in metal-organic frameworks.

The utility of mechanical metamaterials for biomedical applications has seldom been explored. Here we show that a metamaterial that is mechanically responsive to antibody-mediated biorecognition can serve as an optical interferometric mask to molecularly profile extracellular vesicles in ascites fluid from patients with cancer. The metamaterial consists of a hydrogel responsive to temperature and redox activity functionalized with antibodies to surface biomarkers on extracellular vesicles, and is patterned into micrometric squares on a gold-coated glass substrate. Through plasmonic heating, the metamaterial is maintained in a transition state between a relaxed form and a buckled state. Binding of extracellular vesicles from the patient samples to the antibodies on the hydrogel causes it to undergo crosslinking, induced by free radicals generated via the activity of horseradish peroxidase conjugated to the antibodies. Hydrogel crosslinking causes the metamaterial to undergo fast chiral re-organization, inducing amplified changes in its mechanical deformation and diffraction patterns, which are detectable by a smartphone camera. The mechanical metamaterial may find broad utility in the sensitive optical immunodetection of biomolecules.

Biologically templated plasmonics enables simultaneous biophysical and biomolecular analysis of exosome biomarkers., Exosomes are nanoscale vesicles distinguished by characteristic biophysical and biomolecular features; current analytical approaches, however, remain univariate. Here, we develop a dedicated platform for multiparametric exosome analysis—through simultaneous biophysical and biomolecular evaluation of the same vesicles—directly in clinical biofluids. Termed templated plasmonics for exosomes, the technology leverages in situ growth of gold nanoshells on vesicles to achieve multiselectivity. For biophysical selectivity, the nanoshell formation is templated by and tuned to distinguish exosome dimensions. For biomolecular selectivity, the nanoshell plasmonics locally quenches fluorescent probes only if they are target-bound on the same vesicle. The technology thus achieves multiplexed analysis of diverse exosomal biomarkers (e.g., proteins and microRNAs) but remains unresponsive to nonvesicle biomarkers. When implemented on a microfluidic, smartphone-based sensor, the platform is rapid, sensitive, and wash-free. It not only distinguished biomarker organizational states in native clinical samples but also showed that the exosomal subpopulation could more accurately differentiate patient prognosis.

Retroperitoneal sarcomas are characterized by a lack of early symptoms; the inevitable delay in diagnosis results in large sizes at presentation. The current standard of care for these tumours is complete oncological resection with microscopically negative margins. In a subset of these tumours, major vessels such as the inferior vena cava or aorta are involved and resection of these major vessels becomes necessary for complete oncological clearance. This paper describes a series of these tumours and demonstrates the feasibility of radical surgery and resection of major vessels with low morbidity.