Microscale Magnetic Field Modulation for Enhanced Capture and Distribution of Rare Circulating Tumor Cells

Immunomagnetic assay combines the powers of the magnetic separation and biomarker recognition and has been an effective tool to perform rare Circulating Tumor Cells detection. Key factors associated with immunomagnetic assay include the capture rate, which indicates the sensitivity of the system, and distributions of target cells after capture, which impact the cell integrity and other biological properties that are critical to downstream analyses. Here we present a theoretical framework and technical approach to implement a microscale magnetic immunoassay through modulating local magnetic field towards enhanced capture and distribution of rare cancer cells. Through the design of a two-dimensional micromagnet array, we characterize the magnetic field generation and quantify the impact of the micromagnets on rare cell separation. Good agreement is achieved between the theory and experiments using a human colon cancer cell line (COLO205) as the capture targets

Fabrication of monodisperse magnetic nanorods for improving hyperthermia efficacy

Background: Hyperthermia is one of the promising cancer treatment strategies enabled by local heating with the use of tumor-targeting magnetic nanoparticles (MNP) under a non-invasive magnetic field. However, one of the remaining challenges is how to achieve therapeutic levels of heat (without causing damages to regular tissues) in tumors that cannot be effectively treated with anti-tumor drug delivery. Results: In this work, we report a facile method to fabricate magnetic nanorods for hyperthermia by one-step wet chemistry synthesis using 3-Aminopropyltrimethoxysilane (APTMS) as the shape-controlling agent and ferric and ferrous ions as precursors. By adjusting the concentration of APTMS, hydrothermal reaction time, ratios of ferric to ferrous ions, magnetic nanorods with aspect ratios ranging from 4.4 to 7.6 have been produced. At the clinically recommended field strength of 300 Oe (or less) and the frequency of 184 kHz, the specific absorption rate (SAR) of these nanorods is approximately 50 % higher than that of commercial Bionized NanoFerrite particles. Conclusions: This increase in SAR, especially at low field strengths, is crucial for treating deep tumors, such as pancreatic and rectal cancers, by avoiding the generation of harmful eddy current heating in normal tissues.[Figure not available: see fulltext.

Screening and Molecular Analysis of Single Circulating Tumor Cells Using Micromagnet Array

Immunomagnetic assay has been developed to detect rare circulating tumor cells (CTCs), which shows clinical significance in cancer diagnosis and prognosis. The generation and fine-tuning of the magnetic field play essential roles in such assay toward effective single-cell-based analyses of target cells. However, the current assay has a limited range of field gradient, potentially leading to aggregation of cells and nanoparticles. Consequently, quenching of the fluorescence signal and mechanical damage to the cells may occur, which lower the system sensitivity and specificity. We develop a micromagnet-integrated microfluidic system for enhanced CTC detection. The ferromagnetic micromagnets, after being magnetized, generate localized magnetic field up to 8-fold stronger than that without the micromagnets, and strengthen the interactions between CTCs and the magnetic field. The system is demonstrated with four cancer cell lines with over 97% capture rate, as well as with clinical samples from breast, prostate, lung, and colorectal cancer patients. The system captures target CTCs from patient blood samples on a standard glass slide that can be examined using the fluorescence in-situ hybridization method for the single-cell profiling. All cells showed clear hybridization signals, indicating the efficacy of the compact system in providing retrievable cells for molecular studies

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Rational design of on-chip gold plasmonic nanoparticles towards ctDNA screening

This paper demonstrates the design, synthesis, simulation, and testing of three distinct geometries of plasmonic gold nanoparticles for on-chip DNA screening towards liquid biopsy. By employing a seed-mediated growth method, we have synthesized gold nanospheres, nanorods, and nanobipyramids. In parallel, we developed numerical simulations to understand the effects of nanoparticle geometry on the resonance features and refractive index sensitivity. Both experimental and simulation results were compared through a series of studies including in-solution and on-chip tests. We have thoroughly characterized the impact of nanoparticle geometry on the sensitivity to circulating tumor DNA, with immediate implications for liquid biopsy. The results agree well with theoretical predictions and simulations, including both bulk refractive index sensitivity and thin film sensitivity. Importantly, this work quantitatively establishes the link between nanoparticle geometry and efficacy in detecting rare circulating biomarkers. The nanobipyramids provided the highest sensitivity, approximately doubling the sensitivity compared to nanorods. To the best of our knowledge this is the first report carrying through geometric effects of simulation to clinically relevant biosensing. We put forth here synthesis and testing of three nanoparticle geometries, and a framework for both experimental and theoretical validation of plasmonic sensitivities towards liquid biopsy

An Immunofluorescence-assisted Microfluidic Single Cell Quantitative Reverse Transcription Polymerase Chain Reaction Analysis of Tumour Cells Separated from Blood

Circulating tumour cells (CTCs) are important indicators of metastatic cancer and may provide critical information for individualized treatment. As CTCs are usually very rare, the techniques to obtain information from very small numbers of cells are crucial. Here, we propose a method to perform a single cell quantitative reverse transcription polymerase chain reaction (qPCR) analysis of rare tumour cells. We utilized a microfluidic immunomagnetic assay to separate cancer cells from blood. A combination of detailed immunofluorescence and laser microdissection enabled the precise selection of individual cells. Cancer cells that were spiked into blood were successfully separated and picked up for a single cell PCR analysis. The breast cancer cell lines MCF7, SKBR3 and MDAMB231 were tested with 10 different genes. The result of the single cell analysis matched the results from a few thousand cells. Some markers (e.g., ER, HER2) that are commonly used for cancer identification showed relatively large deviations in expres‐ sion levels. However, others (e.g., GRB7) showed devia‐ tions that are small enough to supplement single cell disease profiling

Full wave simulations of fast wave efficiency and power losses in the scrape-off layer of tokamak plasmas in mid/high harmonic and minority heating regimes

Several experiments on different machines and in different fast wave (FW) heating regimes, such as hydrogen minority heating and high harmonic fast waves (HHFW), have found strong interaction between radio-frequency (RF) waves and the scrape-off layer (SOL) region. This paper examines the propagation and the power loss in the SOL by using the full wave code AORSA, in which the edge plasma beyond the last closed flux surface (LCFS) is included in the solution domain and a collisional damping parameter is used as a proxy to represent the real, and most likely nonlinear, damping processes. 2D and 3D AORSA results for the National Spherical Torus eXperiment (NSTX) have shown a strong transition to higher SOL power losses (driven by the RF field) when the FW cut-off is removed from in front of the antenna by increasing the edge density. Here, full wave simulations have been extended for 'conventional' tokamaks with higher aspect ratios, such as the DIII-D, Alcator C-Mod, and EAST devices. DIII-D results in HHFW regime show similar behavior found in NSTX and NSTX-U, consistent with previous DIII-D experimental observations. In contrast, a different behavior has been found for C-Mod and EAST, which operate in the minority heating regime.United States. Department of Energy. Office of Fusion Energy Sciences (Contract DE-FC02-01ER54648)United States. Department of Energy. Office of Fusion Energy Sciences (Contract DE-AC02-09CH11466)United States. Department of Energy. Office of Fusion Energy Sciences (Contract DE-AC05-00OR22725)United States. Department of Energy. Office of Fusion Energy Sciences (Contract DE-AC02-05CH11231