Ocean NanoTech (United States)

Supercritical carbon dioxide (SCCO2) offers multiple advantages such as low processing temperature and an oxygen-free processing environment for applications like drying food side streams and extracting lipids and bioactives. In this work, SCCO2 drying was investigated for four food side streams, including SBP (soybean pulp), brewer’s spent grain (BSG), spent coffee grounds (SCG), and cranberry pomace (CBP). The Taguchi method was used to systematically vary the processing parameters (pressure, temperature, flow rate, and extraction time) to assess their impact on moisture removal. SCCO2 drying extracted around 83–90% of the water from food side streams without affecting the properties of high-value products within the side streams. Optimal drying conditions were found to be at 100 bar and 70 °C for BSG and SCG, at 200 bar and 70 °C for SBP, and at 100 bar and 60 °C for CBP, with drying times and flow rates of CO2 ranging from 2.5 to 3 h and 90 to 150 g/min, respectively. Following drying, a sequential extraction strategy was implemented: neat SCCO2 was initially employed to extract lipids, followed by ethanol injections to recover leftover lipids and ethanol-soluble bioactives and, subsequently, sequential injections of 70% ethanol and water to extract the remaining bioactives. Nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry (LC–MS) analyses of each fraction collected from CBP demonstrated that SCCO2 not only enabled efficient drying and concurrent extraction of water-soluble bioactives but also allowed for stepwise lipid extraction and selective fractionation of bioactives at each stage. This integrated, one-pot SCCO2 process offers a sustainable and efficient approach for the comprehensive valorization of high-moisture food side streams.

Magnetic hyperthermia therapy is an evolving treatment for tumors where magnetic nanoparticles (MNPs) are directed to the tumor and exposed to an alternating magnetic field (AMF). This induces localized heating, causing the apoptosis of cancer cells. Monitoring heat delivery in a noninvasive, real-time manner is crucial for predicting clinical outcomes. This precise control over the hyperthermia process allows for targeted temperature adjustments in the range of 42 °C–46 °C, effectively targeting cancer cells while minimizing damage to surrounding healthy tissue. Factors, such as MNP size, medium viscosity, and AMF frequency and amplitude, influence the hyperthermia performance. Optimizing these factors enhances heat dissipation through mechanisms, such as hysteresis loss and Néel and Brownian relaxations, improving the intrinsic loss power (ILP) of the MNPs. In this study, we meticulously measure the temperature–time curves (T–t curves) and ILP values of several commercially available iron oxide MNP products. By systematically varying the concentration and magnetic core size of the MNPs and tuning the frequency and amplitude of the AMF, we aim to elucidate how these factors collectively influence heat dissipation. This, in turn, enhances our understanding of the optimal conditions for in vivo hyperthermia treatment. Our results indicate that among the MNP products tested, the 30 nm single-core MNPs exhibited the highest ILP. Additionally, for different MNP concentrations, the 50 nm multi-core MNPs show the highest ILP at a concentration of 2 mg/mL.

Abstract Magnetic particle imaging (MPI) is a tracer-based tomographic imaging technique utilized in applications such as lung perfusion imaging, cancer diagnosis, stem cell tracking, etc. The goal of translating MPI to clinical use has prompted studies on further improving the spatial-temporal resolutions of MPI through various methods, including image reconstruction algorithm, scanning trajectory design, magnetic field profile design, and tracer design. Iron oxide magnetic nanoparticles (MNPs) are favored for MPI and magnetic resonance imaging (MRI) over other materials due to their high biocompatibility, low cost, and ease of preparation and surface modification. For core–shell MNPs, the tracers’ magnetic core size and non-magnetic coating layer characteristics can significantly affect MPI signals through dynamic magnetization relaxations. Most works to date have assumed an ensemble of MNP tracers with identical sizes, ignoring that artificially synthesized MNPs typically follow a log-normal size distribution, which can deviate theoretical results from experimental data. In this work, we first characterize the size distributions of four commercially available iron oxide MNP products and then model the collective magnetic responses of these MNPs for MPI applications. For an ensemble of MNP tracers with size standard deviations of σ, we applied a stochastic Langevin model to study the effect of size distribution on MPI imaging performance. Under an alternating magnetic field (AMF), i.e., the excitation field in MPI, we collected the time domain dynamic magnetizations (M-t curves), magnetization-field hysteresis loops (M-H curves), point-spread functions (PSFs), and higher harmonics from these MNP tracers. The intrinsic MPI spatial resolution, which is related to the full width at half maximum (FWHM) of the PSF profile, along with the higher harmonics, serve as metrics to provide insights into how the size distribution of MNP tracers affects MPI performance.

Magnetic Particle Spectroscopy (MPS) originates from Magnetic Particle Imaging (MPI) and was initially designed to assess the suitability of magnetic nanoparticle tracers for MPI applications. Since 2006, MPS has found application in bioassays. It relies on detecting the magnetic dynamics of magnetic nanoparticles in bioassay contexts. When exposed to an external sinusoidal magnetic drive field, magnetic nanoparticles exhibit magnetization relaxation, aligning their magnetic moments with the field direction through Brownian and Néel relaxations. Their nonlinear magnetization responses induce higher harmonics of the drive field frequency, revealing information about the nanoparticles' biological environment. Throughout its development, various MPS designs have been reported. Herein, I will cover the dynamic magnetization models of magnetic nanoparticles and the surface functionalization of these nanoparticles for MPS-based bioassays. In addition, different MPS platforms will be explored, including single- and dual-driving field designs and MPS assay mechanisms such as volumetric- and surface-based bioassays. The integration of MPS with lateral flow assays and microfluidic channels will also be discussed. Various examples of MPS-based bioassays for detecting viruses (e.g., influenza A virus, SARS-CoV-2) and foodborne pathogens/toxins will be showcased.

In recent years, magnetic particle spectroscopy (MPS) has become a highly sensitive and versatile sensing technique for quantitative bioassays. It relies on the dynamic magnetic responses of magnetic nanoparticles (MNPs) for the detection of target analytes in the liquid phase. There are many research studies reporting the application of MPS for detecting a variety of analytes including viruses, toxins, nucleic acids, and so forth. Herein, we report a modified version of the MPS platform with the addition of a one-stage lock-in design to remove the feedthrough signals induced by external driving magnetic fields, thus capturing only MNP responses for improved system sensitivity. This one-stage lock-in MPS system is able to detect as low as 781 ng multi-core Nanomag50 iron oxide MNPs (micromod Partikeltechnologie GmbH) and 78 ng single-core SHB30 iron oxide MNPs (Ocean NanoTech). We first demonstrated the performance of this MPS system for bioassay-related applications. Using the SARS-CoV-2 spike protein as a model, we have achieved a detection limit of 125 nM (equal to 5 pmole) for detecting spike protein molecules in the liquid phase. In addition, using a streptavidin-biotin binding system as a proof-of-concept, we show that these single-core SHB30 MNPs can be used for Brownian relaxation-based bioassays while the multi-core Nanomag50 cannot be used. The effects of MNP amount on the concentration-dependent response profiles for detecting streptavidin were also investigated. Results show that by using a lower concentration/ amount of MNPs, concentration-response curves shift to a lower concentration/amount of target analytes. This lower concentration-response indicates the possibility of improved bioassay sensitivities by using lower amounts of MNPs.

Magnetic nanoparticles (MNPs) have been extensively used as tiny heating sources in magnetic hyperthermia therapy, contrast agents in magnetic resonance imaging, tracers in magnetic particle imaging, carriers for drug/gene delivery, etc. There have emerged many MNP/microbead suppliers since the past decade, such as Ocean NanoTech, Nanoprobes, US Research Nanomaterials, Miltenyi Biotec, micromod Partikeltechnologie GmbH, nanoComposix, and so forth. In this paper, we report the physical and magnetic characterizations on iron oxide nanoparticle products from Ocean NanoTech. Standard characterization tools such as vibrating-sample magnetometry, X-ray diffraction, dynamic light scattering, transmission electron microscopy, and zeta potential analysis are used to provide MNP customers and researchers with an overview of these iron oxide nanoparticle products. In addition, the dynamic magnetic responses of these iron oxide nanoparticles in aqueous solutions are investigated under low- and high-frequency alternating magnetic fields, giving a standardized operating procedure for characterizing the MNPs from Ocean NanoTech, thereby yielding the best of MNPs for different applications.

Abstract Purpose: We sought to use combretastatin A-4 phosphate disodium (CA4P) to enhance the tumor uptake of doxorubicin (Dox)-loaded, polyethylene glycol (PEG)-coated hollow gold nanospheres (HAuNS; Dox@PEG-HAuNS) for improved photothermal ablation (PTA)-chemotherapy of hepatocellular carcinoma (HCC) in rats under image guidance. Materials and Methods: Two groups of 10 HCC-bearing rats each received intrahepatic arterial (IA) injection of either PEG-HAuNS/Lipiodol alone or CA4P followed by PEG-HAuNS/Lipiodol 5 min later. Each group was subdivided, and the Au content of tumors and tissues excised at 1 h or at 24 h was quantified using neutron activation analysis (n = 5/time point). Five rats received CA4P plus PEG-[64Cu]-HAuNS/Lipiodol and underwent μPET/CT. Therapeutic effects were compared among 3 groups of 6 rats each that received IA injection of saline (control group), CA4P plus Dox@PEG-HAuNS/Lipiodol (chemotherapy group), or CA4P plus Dox@PEG-HAuNS/Lipiodol plus near-infrared irradiation (PTA-chemotherapy group). Findings were verified with postmortem histopathology and/or autoradiography. Results: PEG-HAuNS uptake in CA4P-pretreated tumors was significantly higher than that in non-CA4P-pretreated tumors at both 1 h (P<0.05) and 24 h (P<0.01). The tumor-to-liver PEG-HAuNS uptake ratios at 1 h and 24 h were 5.63±3.09 and 1.68±0.77, respectively, in the CA4P-treated group and 1.29±2.40 and 0.14±0.11, respectively, in the non-CA4P-treated group. μPET/CT clearly delineated the tumors, enabling quantitative imaging guidance. Tumor volumes 10 d after therapy were 1.68±1.01, 3.96±1.75, and 6.13±2.27 cm3 in the PTA-chemotherapy, chemotherapy, and control groups, respectively, with significant differences between the PTA-chemotherapy group and other groups (P<0.05). Conclusion: CA4P pretreatment causes a higher concentration of Dox@PEG-HAuNS to be trapped inside the tumor, thereby enhancing the anti-HCC efficacy of μPET/CT-guided PTA-chemotherapy in rats. (Supported in part by the John S. Dunn Foundation) Citation Format: Junjie Li, Min Zhou, Chiyi Xiong, Wanqin Wang, Qizhen Cao, Xiaoxia Wen, Xin Ji, Andrew Wang, Sanjay Gupta, Chun Li. Intraarterial delivery of doxorubicin-loaded hollow gold nanospheres for photothermal ablation chemotherapy of hepatocellular carcinoma in the liver of rats. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4204.