Glioblastomas shed large quantities of small, membrane-bound microvesicles (MVs) into the circulation. While these hold promise as potential biomarkers of therapeutic response, their identification and quantitation remain challenging. Here, we describe a highly sensitive and rapid analytical technique for profiling circulating MVs directly from blood samples of glioblastoma patients. MVs, introduced onto a dedicated microfluidic chip, are labeled with target-specific magnetic nanoparticles and detected by a miniaturized nuclear magnetic resonance system. Compared with current methods, this integrated system has a much higher detection sensitivity, and can differentiate glioblastoma multiforme (GBM) MVs from non-tumor host cell-derived MVs. We also show that circulating GBM MVs can serve as a surrogate for primary tumor mutations and a predictive metric of treatment-induced changes. This platform could provide both an earlier indicator of drug efficacy and a potential molecular stratifier for human clinical trials.

Real-time monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major clinical problem as serial re-biopsy of primary tumors is often not a clinical option. MGMT (O6-alkylguanine DNA alkyltransferase) and APNG (alkylpurine-DNA-N-glycosylase) are key enzymes capable of repairing temozolomide-induced DNA damages and their levels in tissue are inversely related to treatment efficacy. Yet, serial clinical analysis remains difficult and when done, primarily relies on promoter methylation studies of tumor biopsy material at the time of initial surgery. Here we present a microfluidic chip to analyze mRNA levels of MGMT and APNG in enriched tumor exosomes obtained from blood. We show that exosomal mRNA levels of these enzymes correlate well with levels found in parental cells and that levels change considerably during treatment of seven patients. We propose that if validated on a larger cohort of patients, the method may be used to predict drug response in GBM patients.

The ability to detect rare cells (< 100 cells per ml of whole blood) and obtain quantitative measurements of specific biomarkers on single cells is increasingly important in basic biomedical research. Implementing such methodology for widespread use in the clinic, however, has been hampered by low cell density, small sample sizes, and requisite sample purification. To overcome these challenges, we have developed a microfluidic chip-based micro-Hall detector (μHD), which can directly measure single, immunomagnetically tagged cells in whole blood. The μHD can detect single cells even in the presence of vast numbers of blood cells and unbound reactants, and does not require any washing or purification steps. In addition, the high bandwidth and sensitivity of the semiconductor technology used in the μHD enables high-throughput screening (currently ~107 cells/min). The clinical utility of the μHD chip was demonstrated by detecting circulating tumor cells in whole blood of 20 ovarian cancer patients at higher sensitivity than currently possible with clinical standards. Furthermore, the use of a panel of magnetic nanoparticles, distinguished with unique magnetization properties and bio-orthogonal chemistry, allowed simultaneous detection of the biomarkers EpCAM, HER2/neu, and EGFR on individual cells. This cost-effective, single-cell analytical technique is well-suited to perform molecular and cellular diagnosis of rare cells in the clinic.

Electrocatalytic CO2 conversion into fuel is a prospective strategy for the sustainable energy production. However, still many parts of the catalyst such as low catalytic activity, selectivity, and stability are challenging. Herein, a hierarchical hexagonal Zn catalyst showed highly efficient and, more importantly, stable performance as an electrocatalyst for selectively producing CO. Moreover, we found that its high selectivity for CO is attributed to morphology. In electrochemical analysis, Zn (101) facet is favorable to CO formation whereas Zn (002) facet favors the H2 evolution during CO2 electrolysis. Indeed, DFT calculations showed that (101) facet lowers a reduction potential for CO2 to CO by more effectively stabilizing a (.) COOH intermediate than (002) facet. This further suggests that tuning the crystal structure to control (101)/(002) facet ratio of Zn can be considered as a key design principle to achieve a desirable product from Zn catalyst.

A new nanocrystalline sensitizer with the chemical formula (CH 3 CH 2 NH 3 )PbI 3 is synthesized by reacting ethylammonium iodide with lead iodide, and its crystal structure and photovoltaic property are investigated. X-ray diffraction analysis confirms orthorhombic crystal phase with a = 8.7419(2) Å, b = 8.14745(10) Å, and c = 30.3096(6) Å, which can be described as 2 H perovskite structure. Ultraviolet photoelectron spectroscopy and UV-visible spectroscopy determine the valence band position at 5.6 eV versus vacuum and the optical bandgap of ca. 2.2 eV. A spin coating of the CH 3 CH 2 NH 3 I and PbI 2 mixed solution on a TiO 2 film yields ca. 1.8-nm-diameter (CH 3 CH 2 NH 3 ) PbI 3 dots on the TiO 2 surface. The (CH 3 CH 2 NH 3 )PbI 3 -sensitized solar cell with iodide-based redox electrolyte demonstrates the conversion efficiency of 2.4% under AM 1.5 G one sun (100 mW/cm 2 ) illumination.

Catalysis is a key technology for the synthesis of renewable fuels through electrochemical reduction of CO2 . However, successful CO2 reduction still suffers from the lack of affordable catalyst design and understanding the factors governing catalysis. Herein, we demonstrate that the CO2 conversion selectivity on Sn (or SnOx /Sn) electrodes is correlated to the native oxygen content at the subsurface. Electrochemical analyses show that the reduced Sn electrode with abundant oxygen species effectively stabilizes a CO2 (.-) intermediate rather than the clean Sn surface, and consequently results in enhanced formate production in the CO2 reduction. Based on this design strategy, a hierarchical Sn dendrite electrode with high oxygen content, consisting of a multi-branched conifer-like structure with an enlarged surface area, was synthesized. The electrode exhibits a superior formate production rate (228.6 μmol h(-1)  cm(-2) ) at -1.36 VRHE without any considerable catalytic degradation over 18 h of operation.

Objective The goal of this study is to characterize resident cardiac stem cells (CSCs) and investigate their therapeutic efficacy in myocardial infarction by molecular imaging methods. Background CSCs have been isolated and characterized in vitro. These cells offer a provocative method to regenerate the damaged myocardium. However, the survival kinetics and function of transplanted CSCs have not been fully elucidated. Methods CSCs were isolated from L2G85 transgenic mice (FVB background) that constitutively express both firefly luciferase (Fluc) and enhanced green fluorescence protein (eGFP) reporter gene. CSCs were characterized in vitro and transplanted in vivo into murine infarction models. Multi-modality noninvasive imaging techniques were used to assess CSC survival and therapeutic efficacy for restoration of cardiac function. Results CSCs can be isolated from L2G85 mice and FACS analysis showed expression of resident CSCs markers (Sca-1, c-Kit) and mesenchymal stem cell markers (CD90, CD106). Afterwards, 5×105 CSCs (n=30) or PBS control (n=15) was injected into the hearts of syngeneic FVB mice undergoing left anterior descending artery (LAD) ligation. Bioluminescence imaging (BLI) showed poor donor cell survival by week 8. Echocardiogram, invasive hemodynamic pressure-volume (PV) analysis, positron emission tomography (PET) imaging with Fluorine-18-fluorodeoxyglucose ([18F]-FDG), and cardiac magnetic resonance imaging (MRI) demonstrated no significant difference in cardiac contractility and viability between the CSC and control group. Finally, postmortem analysis confirmed transplanted CSCs integrated with host cardiomyocytes by immunohistology. Conclusions In a mouse myocardial infarction (MI) model, Sca-1 positive CSCs provide no long-term engraftment and benefit to cardiac function as determined by multi-modality imaging.

The task of rapidly identifying patients infected with Mycobacterium tuberculosis (MTB) in resource-constrained environments remains a challenge. A sensitive and robust platform that does not require bacterial isolation or culture is critical in making informed diagnostic and therapeutic decisions. Here we introduce a platform for the detection of nucleic acids based on a magnetic barcoding strategy. PCR-amplified mycobacterial genes are sequence-specifically captured on microspheres, labeled by magnetic nanoprobes, and detected by nuclear magnetic resonance. All components are integrated into a single, small fluidic cartridge for streamlined on-chip operation. We use this platform to detect MTB and identify drug-resistance strains from mechanically processed sputum samples within 2.5 hours. The specificity of the assay is confirmed by a panel of clinically relevant non-MTB bacteria, and the clinical utility is demonstrated by the measurements in MTB-positive patient specimens. Combined with portable systems, the magnetic barcode assay holds promise to become a sensitive, high-throughput, and low-cost platform for point-of-care diagnostics.