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Label-free optical detection of insulin would allow in vitro assessment of pancreatic cell functions in their natural state and expedite diabetes-related clinical research and treatment, however no existing method has met these criteria at physiological concentrations. Using spatially-uniform 3D gold-nanoparticle sensors, we have demonstrated surface-enhanced Raman sensing of insulin in the secretions from human pancreatic islets under low and high glucose environments without the use of labels such as antibodies or aptamers. Label-free measurements of the islet secretions showed excellent correlation among the ambient glucose levels, secreted insulin concentrations, and measured Raman-emission intensities. When excited at 785 nm, plasmonic hotspots of the densely-arranged 3D gold-nanoparticle pillars as well as strong interaction between sulphide linkages of the insulin molecules and the gold nanoparticles produced highly sensitive and reliable insulin measurements down to 100 pM. The sensors exhibited a dynamic range of 100 pM to 50 nM with an estimated detection limit of 35 pM, which covers the reported concentration range of insulin observed in pancreatic cell secretions.The sensitivity of this approach is approximately four orders of magnitude greater than previously reported results using label-free optical approaches, and it is much more costeffective than immunoassay-based insulin detection widely used in clinics and laboratories. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3 Hormones are chemical messengers that control a wide variety of functions in the human body. Maintaining adequate hormone levels is extremely important for human health and disruption to these levels can result in life-debilitating conditions. Simple and easy measurements of hormonal secretions ex vivo or in vivo are essential for implementing next generation biosensors, allowing convenient monitoring of health and early disease detection.One of the most prevalent diseases resulting from hormonal dysfunction is diabetes, which arises from a disruption in the release of insulin in the body. 1-2 Insulin is a peptide hormone which is secreted by beta cells, one of five primary cell-types which populate pancreatic cellular clusters known as islets. The concentration of insulin secreted from beta cells in plasma has been reported to vary between 100 pM (fasting) and 2 nM (about 1 hour after glucose intake) in non-diabetic individuals. [3][4] In diabetic individuals, functional damage to the beta cells reduces or inhibits their ability to release insulin. One of the leading methodologies for treatment of type-1 diabetes is pancreatic islet transplantation, where healthy islets harvested from deceased donors are transplanted into diabetic patients. [5][6] Since the number of donors is limited, methodologies that can improve the efficiency and succe...

It is well-known that gold nanoparticle (AuNP) clusters generate strong surface-enhanced Raman scattering (SERS). In order to produce spatially uniform Raman-enhancing substrates at a large scale, we synthesized vertically perforated three-dimensional (3D) AuNP stacks. The 3D stacks were fabricated by first hydrothermally synthesizing ZnO nanowires perpendicular to silicon wafers followed by repetitively performing liquid-phase deposition of AuNPs on the tops and side surfaces of the nanowires. During the deposition process, the nanowires were shown to gradually dissolve away, leaving hollow vestiges or perforations surrounded by stacks of AuNPs. Simulation studies and experimental measurements reveal these nanoscale perforations serve as light paths that allow the excitation light to excite deeper regions of the 3D stacks for stronger overall Raman emission. Combined with properly sized nanoparticles, this feature maximizes and saturates the Raman enhancement at 1-pM sensitivity across the entire wafer-scale substrate, and the saturation improves the wafer-scale uniformity by a factor of 6 when compared to nanoparticle layers deposited directly on a silicon wafer substrate. Using the 3D-stacked substrates, quantitative sensing of adenine molecules yielded concentrations measurements within 10% of the known value. Understanding the enhancing mechanisms and engineering the 3D stacks have opened a new method of harnessing the intense SERS observed in nanoparticle clusters and realize practical SERS substrates with significantly improved uniformity suitable for quantitative chemical sensing.

Integration of diamond on GaN can ease the challenges associated with thermal management of GaN-based power amplifiers which need to base on highly scaled transistors to push toward higher frequencies at high powers for 5G networks. The integration of diamond was achieved by growing polycrystalline (PC) diamond on nitrogen-polar GaN. A standard 5 nm Si3N4 layer which forms the gate dielectric was used as an interlayer between diamond and the GaN channel for etching protection. Since diamond growth conditions involve high temperature and H2 plasma, it can easily decompose the underlying dielectric as well as the GaN channel and degrade the channel conductivity and hence the device performance. Due to the incompatibility of conventional growth recipes with thin dielectrics (<5 nm), a novel two-stage-three-step growth recipe was designed for PC diamond integration on top of nitrogen-polar GaN high-electron-mobility transistors in a H2/CH4-plasma environment. Using only H2 and CH4 in the chamber guarantees a higher-phase-purity diamond than chambers with added argon or nitrogen for lower substrate etching. This recipe maintains the performance of the two-dimensional-electron gas and provides a less columnar diamond structure with a larger grain size. Our observations were supported by scanning transmission electron microscopy and Hall mobility measurements using the van der Pauw technique before and after diamond growth. A mobility of ∼1250 cm2/V s, a sheet carrier concentration of ∼1.30 × 1013 cm–2, and a sheet resistivity of ∼380 Ω/□ were maintained after the growth of diamond. The anisotropy ratio has been decreased from 3.75 to 1.12 with this growth recipe. Using long channel devices, we measured the difference in the channel temperature, which decreased by more than 100 °C in the range of 10–24 W/mm power after the integration of the diamond on top of the device.