Tumor-derived extracellular vesicles (EVs) hold the potential to substantially improve noninvasive early diagnosis of cancer. However, analysis of nanosized EVs in blood samples has been hampered by lack of effective, rapid, and standardized methods for isolating and detecting EVs. To address this difficulty, here we use the electric-hydraulic analogy to design cascaded microfluidic circuits for pulsatile filtration of EVs via integration of a cell-removal circuit and an EV-isolation circuit. The microfluidic device is solely driven by a pneumatic clock pulse generator, allowing for preprogrammed, clog-free, gentle, high-yield, and high-purity isolation of EVs directly from blood within 30 minutes. We demonstrate its clinical utility by detecting protein markers of isolated EVs from patient blood using a polyethylene glycol–enhanced thermophoretic aptasensor, with 91% accuracy for diagnosis of early-stage breast cancer. The cascaded microfluidic circuits can have broad applications in the field of EV research.

The intracellular delivery of metal-organic frameworks (MOFs) encapsulated with functional biomolecules represents a promising avenue in the field of biomedicine and biosensing. To improve the cellular uptake efficiency of MOFs, here we report the fabrication of cancer cell-derived exosome membrane (EM)-coated zeolitic imidazolate framework-8 (EM-ZIF-8) nanoparticles by using a microfluidic sonication device. EM-ZIF-8 nanoparticles loaded with FITC-labeled bovine serum albumin (BSA) can be taken up by cancer cells and evade phagocytosis more efficiently than their counterparts (ZIF-8 nanoparticles). Moreover, we use EM-ZIF-8 loaded with Rhodamine B (RhB) for in situ imaging of cellular adenosine triphosphate (ATP). The shield effect of ZIF-8 suppresses the fluorescence of RhB, and the presence of ATP disrupts the ZIF-8 structure based on the competitive coordination between ATP and Zn 2+ , leading to the restoration of RhB fluorescence. This method allows accurate detection of the fluctuation of ATP in A549 cells induced by Ca 2+ or 2-DDG treatment. The devised biomimetic EM-ZIF-8 nanoparticles thus provide an efficient platform for intracellular drug delivery and ATP sensing.

The columbite supergroup is established. It includes five mineral groups (ixiolite, wolframite, samarskite, columbite, and wodginite) and one ungrouped species (lithiotantite). The criteria for a mineral to belong to the columbite supergroup are: the general stoichiometry MO2; the crystal structure based on the hexagonal close packing (hcp) of anions (or close to it); the six-fold coordination number of M-type cations (augmented to eight-fold in the case of slight distortion of hcp); and the presence of zig-zag chains of edge-sharing M-centered polyhedra. The ixiolite-type structure is considered as an aristotype with the space group Pbcn, the smallest unit cell volume, and the basic vectors a0, b0, c0. Based on the multiplying of the ixiolite-type unit cell the following derivatives are distinguished: ixiolite type (ixiolite-group minerals; a = a0, b = b0, c = c0; Pbcn; the members are ixiolite-(Mn 2+ ), ixiolite-(Fe 2+ ), scrutinyite, seifertite, and srilankite), wolframite type (wolframite-group minerals, ordered analogs of the ixiolite type with a = a0, b = b0, c = c0; P2/c; the members are ferberite, hübnerite, huanzalaite, sanmartinite, heftetjernite, nioboheftetjernite, rossovskyite, and andriesite), samarskite type (samarskite-group minerals; a = 2a0, b = b0, c = c0; P2/c; the members are samarskite-(Y), ekebergite, and shakhdaraite-(Y)), columbite type (columbite-group minerals; a = 3a0, b = b0, c = c0; Pbcn; the members are columbite-(Fe), columbite-(Mn), columbite-(Mg), tantalite-(Fe), tantalite-(Mn), tantalite-(Mg), fersmite, euxenite-(Y), tanteuxenite-(Y), and uranopolycrase), and wodginite type (wodginite-group minerals; a = 2a0, b = 2b0, c = c0; C2/c; the members are wodginite, ferrowodginite, titanowodginite, ferrotitanowodginite, tantalowodginite, lithiowodginite, and achalaite). Samarskite-(Yb), ishikawaite, and calciosamarskite are insufficiently studied minerals tentatively considered as possible members of the samarskite supergroup. Qitianlingite, yttrocolumbite-(Y), yttrotantalite-(Y), and yttrocrasite-(Y) are questionable minerals which need further studies. Polycrase-(Y) is discredited as a mineral identical with euxenite-(Y). Ixiolite has been renamed to ixiolite-(Mn 2+ ),with the end-member formula (Ta2/3Mn 2+ 1/3)O2. Ta-and Nb-dominant analogues of ixiolite with different schemes of charge balancing have the end-member formulae (M1 5+ 0.5M2 3+ 0.5)O2,