Sensitive detection of extracellular vesicles (EVs) as emerging biomarkers has shown great promises for disease diagnosis. Plasmonic metal nanostructures conjugated with molecules that bind specific biomarker targets are widely used for EVs sensing but involve tradeoffs between particle-size-dependent signal intensity and conjugation efficiency. One solution to this problem would be to induce nucleation on nanoparticles that have successfully bound a target biomarker to permit in situ nanoparticle growth for signal amplification, but approaches that are evaluated to date require harsh conditions or lack nucleation specificity, prohibiting their effective use with most biological specimens. This study describes a one-step in situ strategy to induce monocrystalline copper shell growth on gold nanorod probes without decreasing signal by disrupting probe-target interactions or lipid bilayer integrity to enable EV biomarker detections. This approach increases the detected nanoparticle signal about two orders of magnitude after a 10 min copper nanoshell growth reaction. This has significant implications for improved disease detection, as indicated by the ability of a novel immunoassay using this approach to detect low abundance EVs carrying a pathogen-derived biomarker, after their direct capture from serum, to facilitate the diagnosis of tuberculosis cases in a diagnostically challenging pediatric cohort.

The burgeoning field of nanotechnology aims to create and deploy nanoscale structures, devices, and systems with novel, size-dependent properties and functions. The nanotechnology revolution has sparked radically new technologies and strategies across all scientific disciplines, with nanotechnology now applied to virtually every area of research and development in the US and globally. NanoFlorida was founded to create a forum for scientific exchange, promote networking among nanoscientists, encourage collaborative research efforts across institutions, forge strong industry-academia partnerships in nanoscience, and showcase the contributions of students and trainees in nanotechnology fields. The 2019 NanoFlorida International Conference expanded this vision to emphasize national and international participation, with a focus on advances made in translating nanotechnology. This review highlights notable research in the areas of engineering especially in optics, photonics and plasmonics and electronics; biomedical devices, nano-biotechnology, nanotherapeutics including both experimental nanotherapies and nanovaccines; nano-diagnostics and -theranostics; nano-enabled drug discovery platforms; tissue engineering, bioprinting, and environmental nanotechnology, as well as challenges and directions for future research.

The tumor microenvironment plays a critical role in tumor initiation, progression, metastasis, and drug resistance. However, models recapitulating the complex 3D structure, heterogeneous cell environment, and cell-cell interactions found in vivo are lacking. Herein, we report on a gravitational microfluidic platform (GMP) retrofitted with MEMS sensors, which is integrated with 3D nanofiber scaffold-aided tumoroid culture. The results showed that this GMP for tumoroid growth mimics the tumor microenvironment more precisely than static culture models of colon cancer, including higher drug resistance, enhanced cancer stem cell properties, and increased secretion of pro-tumor cytokines. In addition, the GMP includes an integrated surface acoustic wave-based biosensing to monitor cell growth and pH changes to assess drug efficacy. Thus, this simple-to-use perfused GMP tumoroid culture system for in vitro and ex vivo studies may accelerate the drug development process and be a tool in personalized cancer treatment.

The most vital step in the development of novel and existing surface acoustic wave (SAW)-based sensors and transducers is their design and optimization. Demand for SAW devices has been steadily increasing due to their low cost, portability, and versatility in electronics, telecommunications, and biosensor applications. However, a full characterization of surface acoustic wave biosensors in a three-dimensional (3D) finite element model has not yet been developed. In this study, a novel approach is developed for analyzing shear horizontal Love wave resonator devices. The developed modeling methodology was verified using fabricated devices. A thorough analysis of the 3D model and the experimental device was performed in this study including scattering parameters (S-parameters), reflection coefficient parameters, transmission parameters, and phase velocity. The simulated results will be used as a design guideline for future device design and optimization, which has thus far resulted in close matching between prediction and experimental results. This manuscript is the first to demonstrate a 3D finite element model to correlate the sensitivity of the SAW device with the magnitude of the phase shift, the real and imaginary part of the response, insertion loss, and the frequency shift. The results show that the imaginary part of the response shift has a higher sensitivity compared to other parameters.

Cell photoacoustic detection of acoustic signals has serious problems of transmission loss and difficulty in acquisition. Based on the acoustic transmission characteristics of acoustic supermaterials, the acoustic wave directional transmission model is designed using COMSOL software, and a finite element simulation experiment was carried out. Experiments show that the model designed in this paper has good sound wave focusing and acoustic wave directional transmission effects. According to the specific application in different environments, this paper designs a variety of transmission models with different structures and carries out comparative experiments to verify the influence of complex model structures on the directional transmission of sound waves. At the same time, the experimental analysis of the acoustic wave directional transmission effect of the model under different frequency segments is carried out, and the possibility of acoustic wave logic operation is verified. Models can be applied to high frequency acoustic signal acquisition and sound wave transmission in complex environments. These studies have important significance for the development of cell photoacoustic detection technology and the application of metamaterial structures and have good practical merit.

Surface acoustic wave sensors have the advantage of fast response, low-cost, and wireless interfacing capability and they have been used in the medical analysis, material characterization, and other application fields that immerse the device under a liquid environment. The theoretical analysis of the single guided layer shear horizontal acoustic wave based on the perturbation theory has seen developments that span the past 20 years. However, multiple guided layer systems under a liquid environment have not been thoroughly analyzed by existing theoretical models. A dispersion equation previously derived from a system of three rigidly coupled elastic mass layers is extended and developed in this study with multiple guided layers to analyze how the liquid layer’s properties affect the device’s sensitivity. The combination of the multiple layers to optimize the sensitivity of an acoustic wave sensor is investigated in this study. The Maxwell model of viscoelasticity is applied to represent the liquid layer. A thorough analysis of the complex velocity due to the variations of the liquid layer’s properties and thickness is derived and discussed to optimize multilayer Surface acoustic wave (SAW) sensor design. Numerical simulation of the sensitivity with a liquid layer on top of two guided layers is investigated in this study as well. The parametric investigation was conducted by varying the thicknesses for the liquid layer and the guided layers. The effect of the liquid layer viscosity on the sensitivity of the design is also presented in this study. The two guided layer device can achieve higher sensitivity than the single guided layer counterpart in a liquid environment by optimizing the second guided layer thickness. This perturbation analysis is valuable for Love wave sensor optimization to detect the liquid biological samples and analytes.

该文提出了一种用于展宽Colpitts压控振荡器(VCO)调谐范围(TR)的技术.为了实现宽调谐范围,采用一种可变电容反馈技术,该技术同时可得到优于传统Colpitts VCO的相位噪声.且该结构采用动态正向衬底自偏技术,以实现VCO较低功耗、易于起振的特性.基于90 nm CMOS工艺,设计了一款VCO,其相位噪声为--101.9 dBc/Hz@1 MHz,调谐范围为28.1％,考虑调谐范围的品质因数可达-192.2 dBc/Hz.芯片在1V电压供电下,消耗了5.8 mW,芯片面积为0.45 mm2.

A constitutively increased intracellular pH that is higher than the extracellular pH is emerging as a hallmark of cancer and determining pH could play a significant role in the measurement of drug responsiveness of tumor cells. However, a non-invasive, touch-free and real-time pH sensing as a research tool is lacking and remains a major unmet need. The purpose of the current study is to investigate a microfluidic surface acoustic wave (SAW) sensor platform capable of monitoring pH in cell and tumoroid cultures. A novel multi-layer guided SAW sensor integrated into a microfluidic channel was investigated theoretically and experimentally in detail for pH biosensing. Sensitivity and capability of the layer guided Love wave device was modeled using the finite element simulation. The model was verified experimentally, and a study monitoring pH of cell growth media is presented. This novel pH sensor is based on a 13.91 MHz center frequency SAW device coated with ZnO (500 nm) and IrO2 (30 nm) layers to increase the sensitivity. A change in mechanical and electrical properties of the conductive IrO2 layer was observed resulting from electrical corrosion induced by pH solutions affecting the charge distribution, SAW phase velocity and attenuation. By measuring the frequency shift induced by the change in SAW phase velocity between the test group and control group, the pH value of cell culture media from H460 cancer cell culture plates from day 0 to day 5 can easily be determined. To improve the sensitivity and stability of the sensor, a finite element method was used to optimize the layer thicknesses. Taken together, the results of experiments show the potential application of this device to be integrated with microfluidic channels and used in determining pH changes in longitudinal tumor cell cultures.

Pumping and manipulation of liquids in microfluidic channels are important for many mechanical, chemical and biomedical applications. Surface acoustic wave based devices fabricated on high-efficiency piezoelectric substrates have been recently investigated for mixing and separation application within microfluidic channels. In this paper, we introduce a novel integrated surface acoustic wave based pump for liquid delivery and precise manipulation within a microchannel. The device employs a hydrophobic surface coating (Cytop) in the device design to decrease the friction force and increase the bonding. Contrary to previous surface acoustic wave based pumps which were mostly based on the filling and sucking process, we demonstrate long distance media delivery (up to 8 mm) and high pumping velocity increasing the device's application space and mass production potential. Additionally, the device design does not need precise layers of water and glass between substrate and channel, simplifying the design significantly. In this study, we conducted extensive parametric studies to quantify the effects of the liquid volume pumped, microchannel size, input applied power as well as the existence of hydrophobic surface coating on the pumping velocity and pump performance. Our results indicate that the pumping velocity for a constant liquid volume with the same applied input power can be increased by over 130 % (2.31 vs 0.99 mm/min) by employing a hydrophobic surface coating (Cytop) in a thinner microchannel (250 vs 500 µm) design. This device can be used in circulation, dosing, metering and drug delivery applications which necessitates small-scale precise liquid control and delivery.

采用DK1812卷式纳滤膜,对4种电解质盐(NaCl、MgCl2-、Na2SO4和MgSO4)和4种糖类(葡萄糖、果糖、木糖和乳糖)及其混合溶液分别进行分离实验,系统地研究操作压力和不同料液对膜通量及各溶质截留率的影响.结果表明,单一溶质实验,硫酸盐截留率高于氯盐,且随压力增加,NaCl和MgCl2截留率略有增加,而Na2SO4和MgSO4截留率保持不变;二糖截留率明显高于单糖,且随压力增加,各糖截留率均略有下降.糖盐混合溶液实验,无机盐溶液加入糖后,糖对硫酸盐截留率影响最小;糖溶液加入无机盐后,盐对乳糖截留率影响最小.溶液通量实验时,混合溶液较单一溶质溶液通量有所减小.

Detection and quantification of cell viability and growth in two-dimensional (2D) and three-dimensional (3D) cell cultures commonly involve harvesting of cells and therefore requires a parallel set-up of several replicates for time-lapse or dose–response studies. Thus, developing a non-invasive and touch-free detection of cell growth in longitudinal studies of 3D tumor spheroid cultures or of stem cell regeneration remains a major unmet need. Since surface acoustic waves (SAWs) permit mass loading-based biosensing and have been touted due to their many advantages including low cost, small size and ease of assembly, we examined the potential of SAW-biosensing to detect and quantify cell growth. Herein, we demonstrate that a shear horizontal-surface acoustic waves (SH-SAW) device comprising two pairs of resonators consisting of interdigital transducers and reflecting fingers can be used to quantify mass loading by the cells in suspension as well as within a 3D cell culture platform. A 3D COMSOL model was built to simulate the mass loading response of increasing concentrations of cells in suspension in the polydimethylsiloxane (PDMS) well in order to predict the characteristics and optimize the design of the SH-SAW biosensor. The simulated relative frequency shift from the two oscillatory circuit systems (one of which functions as control) were found to be concordant to experimental data generated with RAW264.7 macrophage and A549 cancer cells. In addition, results showed that SAW measurements per se did not affect viability of cells. Further, SH-SAW biosensing was applied to A549 cells cultured on a 3D electrospun nanofiber scaffold that generate tumor spheroids (tumoroids) and the results showed the device's ability to detect changes in tumor spheroid growth over the course of eight days. Taken together, these results demonstrate the use of SH-SAW device for detection and quantification of cell growth changes over time in 2D suspension cultures and in 3D cell culture models, which may have potential applications in both longitudinal 3D cell cultures in cancer biology and in regenerative medicine.

Carrier localization in InGaN∕GaN multiple-quantum wells (MQWs) with three different well thicknesses was investigated optically using time-integrated and time-resolved microphotoluminescence spectroscopy. An anomalous temperature dependence of the photoluminescence peak energy was observed, as a consequence of local potential fluctuations. The carrier localization was more prominent in the case of MQWs with wide well thickness. The results indicate that the degree of potential fluctuation increases with increasing well thickness. Emission from quantum-dot-like states only became apparent in MQWs with wide well thickness, which supports the assertion that carrier localization in InGaN∕GaN MQWs is due to the formation of quantum dots.