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The superior mass sensitivity of micro-coil technology in Nuclear Magnetic Resonance (NMR) Spectroscopy provides potential for the analysis of extremely small mass-limited samples such as eggs, cells, and tiny organisms. For optimal performance and efficiency, the size of the micro-coil should be tailored to the size of the mass-limited sample of interest, which can be costly as mass-limited samples come in many shapes and sizes. Therefore, rapid and economic micro-coil production methods are needed. One method with great potential is 5-axis Computer Numerical Control (CNC) micro-milling, commonly used in the jewelry industry. Most CNC milling machines are designed to process larger objects and commonly have a precision >25 µm (making the machining of common spiral micro-coils, for example, impossible). Here, a 5-axis MiRA6 CNC milling machine, specifically designed for the jewelry industry, with a 0.3 µm precision was used to produce working planar micro-coils, microstrips, and novel micro-sensor designs, with some tested on the NMR in less than 24 hours after the start of the design process. Sample wells could be built into the micro-sensor and could be machined at the same time as the sensors themselves, in some cases leaving a sheet of Teflon as thin as 10 µm between the sample and sensor. This provides the freedom to produce a wide array of designs and demonstrates 5-axis CNC micro-milling as a versatile tool for the rapid prototyping of NMR micro-sensors. This approach allowed the experimental optimization of a prototype microstrip for the analysis of two intact adult Daphnia magna organisms. In addition, a 3D volume slotted tube resonator was produced that allowed for 2D 1 H-13 C NMR of D. magna neonates and exhibited 1 H sensitivity (nLOD ꙍ 600 = 1.49 nmol s 1/2 ) close to that of double striplines, which themselves offer the best compromise between concentration and mass sensitivity published to date.

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Background: Exosomes are small vesicles produced by almost all cells in the body and found in all biofluids. Cancer cell-derived exosomes are known to have distinct, measurable signatures, applicable for early cancer diagnosis. Despite the present bibliometric studies on "Cancer detection" and "Nanoparticles", no single study exists to deal with "Exosome" bibliometric study. Methods: This bibliometric work investigated the publication trends of "Exosomes" nanoparticles and its application in cancer detection, for the literature from 2008 to July 2019. The data were collected from the Web of Science Core Collection. There were variant visual maps generated to show annual publication, most-relevant authors, sources, countries, topics and keywords. The network analysis of these studies was investigated to evaluate the research trends in the field of exosomes. In addition, the data were qualitatively analyzed according to 22 top-cited articles, illustrating the frequently used subjects and methods in exosomes research area. Results: The results showed that the documents in this field have improved the citation rate. The top-relevant papers are mostly published in Scientific Reports journal which has lost its popularity after 2017, while today, Analytical Chemistry is leading in publishing the most articles related to exosomes. The documents containing keywords of plasma, cells, cancer, biomarkers, and vesicles as keywords plus, are more likely to be published in PLoS One journal. The clustering of the keywords network showed that the keyword theme of "extracellular vesicles" has the highest centrality rate. In global research, USA is the most corresponding country, followed by China, Korea and Australia. Based on the qualitative analysis, the published documents with at least 50 citations have used exosome release, cargo, detection, purification and secretion, as their targets and applied cell culture or isolation as their methods. Conclusion:The bibliometric study on exosomes nanoparticles for cancer detection provides a clear vision of the future research direction and identifies the potential opportunities and challenges. This may lead new researchers to select the proper subfields in exosomerelated research fields.