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At least 37 records · Page 2

Blood Plasma Self-Separation Technologies during the Self-Driven Flow in Microfluidic Platforms

Blood plasma is the most commonly used biofluid in disease diagnostic and biomedical analysis due to it contains various biomarkers. The majority of the blood plasma separation is still handled with centrifugation, which is off-chip and time-consuming. Therefore, in the Lab-on-a-chip (LOC) field, an effective microfluidic blood plasma separation platform attracts researchers’ attention globally. Blood plasma self-separation technologies are usually divided into two categories: active self-separation and passive self-separation. Passive self-separation technologies, in contrast with active self-separation, only rely on microchannel geometry, microfluidic phenomena and hydrodynamic forces. Passive self-separation devices are driven by the capillary flow, which is generated due to the characteristics of the surface of the channel and its interaction with the fluid. Comparing to the active plasma separation techniques, passive plasma separation methods are more considered in the microfluidic platform, owing to their ease of fabrication, portable, user-friendly features. We propose an extensive review of mechanisms of passive self-separation technologies and enumerate some experimental details and devices to exploit these effects. The performances, limitations and challenges of these technologies and devices are also compared and discussed.

59 BASIC BIOLOGICAL SCIENCES↗

Cardiovascular and pulmonary dynamics by quantitative imaging

The accuracy and range of studies on cardiovascular and pulmonary functions can be greatly facilitated if the motions of the underlying organ systems throughout individual cycles can be directly visualized and readily measured with minimum or preferably no effect on these motions. Achievement of this objective requires development of techniques for quantitative noninvasive or minimally invasive dynamic and stop-action imaging of the organ systems. A review of advances in dynamic quantitative imaging of moving organs reveals that the revolutionary value of cross-sectional and three-dimensional images produced by various types of radiant energy such as X-rays and gamma rays, positrons, electrons, protons, light, and ultrasound for clinical diagnostic and biomedical research applications is just beginning to be realized. The fabrication of a clinically useful cross-section reconstruction device with sensing capabilities for both anatomical structural composition and chemical composition may be possible and awaits future development.

Wood, E. H.↗

Diagnostic imaging applications; Proceedings of the Meeting, Amsterdam, Netherlands, October 8, 9, 1984

It is more important than ever that engineers have an understanding of the future needs of clinical and research medicine, and that physicians know somthing about probable future developments in instrumentation capabilities. Only by maintaining such a dialog can the most effective application of technological advances to medicine be achieved. This workshop attempted to provide this kind of information transfer in the limited field of diagnostic imaging. Biomedical research at the Jet Propulsion Laboratory is discussed, taking into account imaging results from space exploration missions, as well as biomedical research tasks based in these technologies. Attention is also given to current and future indications for magnetic resonance in medicine, high speed quantitative digital microscopy, computer processing of radiographic images, computed tomography and its modern applications, position emission tomography, and developments related to medical ultrasound.

Beckenbach, E. S.↗

Determining the size and concentration dependence of gold nanoparticles in vitro cytotoxicity (IC{sub 50}) test using WST-1 assay

Gold nanoparticles (AuNPs) received a great deal of attention for biomedical applications, especially in diagnostic imaging and therapeutics. Even though AuNPs have potential benefits in biomedical applications, the impact of AuNPs on human and environmental health still remains unclear. The use of AuNPs which is a high-atomic-number materials, provide advantages in terms of radiation dose enhancement. However, before this can become a clinical reality, cytotoxicity of the AuNPs has to be carefully evaluated. Cytotoxicity test is a rapid, standardized test that is very sensitive to determine whether the nanoparticles produced are harmful or benign on cellular components. In this work the size and concentration dependence of AuNPs cytotoxicity in breast cancer cell lines (MCF-7) are tested by using WST-1 assay. The sizes of AuNPs tested were 13 nm, 50 nm, and 70 nm. The cells were seeded in the 96-well plate and were treated with different concentrations of AuNPs by serial dilution for each size of AuNPs. The high concentration of AuNPs exhibit lower cell viability compared to low concentration of AuNPs. We quantified the toxicity of AuNPs in MCF-7 cell lines by determining the IC{sub 50} values in WST-1 assays. The IC{sub 50} values (inhibitory concentrations that effected 50% growth inhibition) of 50 nm AuNPs is lower than 13 nm and 70 nm AuNPs. Mean that, 50nm AuNPs are more toxic to the MCF-7 cells compared to smaller and larger sizes AuNPs. The presented results clearly indicate that the cytotoxicity of AuNPs depend not only on the concentration, but also the size of the nanoparticles.

60 APPLIED LIFE SCIENCES↗

DNA Origami Incorporated into Solid-State Nanopores Enables Enhanced Sensitivity for Precise Analysis of Protein Translocations

The rapidly advancing field of nanotechnology is driving the development of precise sensing methods at the nanoscale, with solid-state nanopores emerging as promising tools for biomolecular sensing. Here, this study investigates the increased sensitivity of solid-state nanopores achieved by integrating DNA origami structures, leading to the improved analysis of protein translocations. Using holo human serum transferrin (holo-hSTf) as a model protein, we compared hybrid nanopores incorporating DNA origami with open solid-state nanopores. Results show a significant enhancement in holo-hSTf detection sensitivity with DNA origami integration, suggesting a unique role of DNA interactions beyond confinement. This approach holds potential for ultrasensitive protein detection in biosensing applications, offering advancements in biomedical research and diagnostic tool development for diseases with low-abundance protein biomarkers. Further exploration of origami designs and nanopore configurations promises even greater sensitivity and versatility in the detection of a wider range of proteins, paving the way for advanced biosensing technologies.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

Freestanding high-aspect-ratio gold masks for low-energy, phase-based x-ray microscopy

High-resolution, x-ray phase contrast microscopy, a key technique with promising potential in biomedical imaging and diagnostics, is based on narrow-slit high-aspect-ratio gold gratings. Here we present the development, fabrication details, and experimental testing of the freestanding 10 μm thick gold membrane masks with an array of 0.9–1.5 μm void slit apertures for a novel low-energy x-ray microscope. The overall mask size is 4 mm × 4 mm, with a grating pitch of 7.5 μm, 6.0–6.6 μm wide gold bars are supported by 3 μm wide crosslinks at 400 μm intervals. The fabrication process is based on gold electroplating into a silicon mold coated with various thin films to form a voltage barrier, plating base, and sacrificial layer, followed by the mold removal to obtain the freestanding gold membrane with void slit apertures. We discuss key aspects for the materials and processes, including gold structures homogeneity, residual stresses, and prevention of collapsing of the grid elements. We further demonstrate the possibility to obtain high-resolution, high contrast 2D images of biological samples using an incoherent, rotating anode x-ray tube.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

Hydrogel nanoparticle based immunoassay

An immunoassay device incorporating porous polymeric capture nanoparticles within either the sample collection vessel or pre-impregnated into a porous substratum within fluid flow path of the analytical device is presented. This incorporation of capture particles within the immunoassay device improves sensitivity while removing the requirement for pre-processing of samples prior to loading the immunoassay device. A preferred embodiment is coreshell bait containing capture nanoparticles which perform three functions in one step, in solution: a) molecular size sieving, b) target analyte sequestration and concentration, and c) protection from degradation. The polymeric matrix of the capture particles may be made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle. This device is useful for point of care diagnostic assays for biomedical applications and as field deployable assays for environmental, pathogen and chemical or biological threat identification.

47 OTHER INSTRUMENTATION↗

Optical emission spectroscopic diagnostics of a non-thermal atmospheric pressure helium-oxygen plasma jet for biomedical applications

In this work, we have applied optical emission spectroscopy diagnostics to investigate the characteristics of a non-thermal atmospheric pressure helium plasma jet. The discharge characteristics in the active and afterglow region of the plasma jet, that are critical for biomedical applications, have been investigated. The voltage-current characteristics of the plasma discharge were analyzed and the average plasma power was measured to be around 18 W. The effect of addition of small fractions of oxygen at 0.1%-0.5% on the plasma jet characteristics was studied. The addition of oxygen resulted in a decrease in plasma plume length due to the electronegativity property of oxygen. Atomic and molecular lines of selected reactive plasma species that are considered to be useful to induce biochemical reactions such as OH transitions A{sup 2}{Sigma}{sup +}({nu}=0,1){yields}X{sup 2}{Pi}({Delta}{nu}=0) at 308 nm and A{sup 2}{Sigma}{sup +}({nu}=0,1){yields}X{sup 2}{Pi}({Delta}{nu}=1) at 287 nm, O I transitions 3p{sup 5}P{yields}3s{sup 5}S{sup 0} at 777.41 nm, and 3p{sup 3}P{yields}3s{sup 3}S{sup 0} at 844.6 nm, N{sub 2}(C-B) second positive system with electronic transition C{sup 3}{Pi}{sub u}{sup {yields}}B{sup 3}{Pi}{sub g}'' in the range of 300-450 nm and N{sub 2}{sup +}(B-X) first negative system with electronic transition B{sup 2}{Sigma}{sub u}{sup +}{yields}X{sup 2}{Sigma}{sub g}{sup +}({Delta}{nu}=0) at 391.4 nm have been studied. The atomic emission lines of helium were identified, including the He I transitions 3p{sup 3}P{sup 0}{yields}2s{sup 3}S at 388.8 nm, 3p{sup 1}P{sup 0}{yields} 2s{sup 1}S at 501.6 nm, 3d{sup 3}D{yields}2p{sup 3}P{sup 0} at 587.6 nm, 3d{sup 1}D{yields}2p{sup 1}P{sup 0} at 667.8 nm, 3s{sup 3}S{sup 1}{yields}2p{sup 3}P{sup 0} at 706.5 nm, 3s{sup 1}S{sup 0}{yields}2p{sup 1}P{sup 0} at 728.1 nm, and H{sub {alpha}} transition 2p-3d at 656.3 nm. Using a spectral fitting method, the OH radicals at 306-312 nm, the rotational and vibrational temperatures equivalent to gas temperatures of the discharge was measured and the effective non-equilibrium nature of the plasma jet was demonstrated. Our results show that, in the entire active plasma region, the gas temperature remains at 310 {+-} 25 K and 340 {+-} 25 K and it increases to 320 {+-} 25 K and 360 {+-} 25 K in the afterglow region of the plasma jet for pure helium and helium/oxygen (0.1%) mixture, respectively. Additionally, the vibrational temperatures range from 2200 {+-} 100 K and 2500 {+-} 100 K for pure helium and helium/oxygen (0.1%) mixture, respectively. The plasma jet was tested on heat sensitive polymer films used in biomedical applications such as polyethylene terephthalate and poly-L-lactide samples continuously for several minutes without causing any physical or thermal damage to the films. The plasma jet produces significant reactive species of interest while the gas temperatures remain very low demonstrating its potential for a range of biomedical applications.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Quantum dots in nanomedicine: recent trends, advances and unresolved issues

The review addresses the current state of progress in the use of ultra-small nanoparticles from the category of quantum dots (QDs), which presently embraces a widening range of nanomaterials of different nature, including “classical” semiconductor groups III-V and II-VI nanocrystals, along with more recently emerged carbon, silicon, gold and other types of nanoparticles falling into this class of nanomaterials due to their similar physical characteristics such as small size and associated quantum confinement effects. A diverse range of QDs applications in nanomedicine has been extensively summarised previously in numerous publications. Therefore, this review is not intended to provide an all-embracing survey of the well documented QDs uses, but is rather focused on the most recent emerging developments, concepts and outstanding unresolved problematic and sometimes controversial issues. Over 125 publications are overviewed and discussed here in the context of major nanomedicine domains, i.e. medical imaging, diagnostics, therapeutic applications and combination of them in multifunctional theranostic systems. - Highlights: • New types of nanomaterials have been recently added to the category of QDs with a potential in nanomedicine. • Within the main nanomedicine domains, best progress has been achieved with QDs for diagnostic tools. • Further studies are required for the theranostic QDs-based leads to reach clinical translation.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

Nanowell-mediated multidimensional separations combining nanoLC with SLIM IM-MS for rapid, high-peak-capacity proteomic analyses

Mass spectrometry (MS)–based analysis of complex biological samples is essential for biomedical research and clinical diagnostics. The separation prior to MS plays a key role in the overall analysis, with separations having larger peak capacities often leading to more identified species and improved confidence in those identifications. High-resolution ion mobility (IM) separations enabled by Structures for Lossless Ion Manipulation (SLIM) can provide extremely rapid, high-resolution separations and are well suited as a second dimension of separation following nanoscale liquid chromatography (nanoLC). However, existing sample handling approaches for offline coupling of separation modes require microliter-fraction volumes and are thus not well suited for analysis of trace biological samples. We have developed a novel nanowell-mediated fractionation system that enables nanoLC-separated samples to be efficiently preconcentrated and directly infused at nanoelectrospray flow rates for downstream analysis. When coupled with SLIM IM-MS, the platform enables rapid and high-peak-capacity multidimensional separations of small biological samples. In this study, peptides eluting from a 100 nL/min nanoLC separation were fractionated into ~?60 nanowells on a microfluidic glass chip using an in-house–developed robotic system. The dried samples on the chip were individually reconstituted and ionized by nanoelectrospray for SLIM IM-MS analysis. Using model peptides for characterization of the nanowell platform, we found that at least 80% of the peptide components of the fractionated samples were recovered from the nanowells, providing up to ~tenfold preconcentration for SLIM IM-MS analysis. The combined LC-SLIM IM separation peak capacities exceeded 3600 with a measurement throughput that is similar to current one-dimensional (1D) LC-MS proteomic analyses.

Dou, Maowei↗

Percutaneous Transhepatic Endoscopic Holmium Laser Lithotripsy for Intrahepatic and Choledochal Biliary Stones

Purpose: To report our approach for treating complicated biliary calculi by percutaneous transhepatic endoscopic biliary holmium laser lithotripsy (PTBL). Patients and Methods: Twenty-two symptomatic patients (11 men and 11 women, age range 51 to 88 years) with intrahepatic or common bile duct calculi underwent PTBL. Nine patients had undergone previous gastrectomy and small-bowel anastomosis, thus precluding endoscopic retrograde cholangiopancreatography. In the other 13 patients, stone removal attempts by ERCP failed due to failed access or very large calculi. We used a 7.5F flexible ureteroscope and a 200-{mu}m holmium laser fiber by way of a percutaneous transhepatic tract, with graded fluoroscopy, to fragment the calculi with direct vision. Balloon dilatation was added when a stricture was seen. The procedure was performed with the patient under general anaesthesia. A biliary drainage tube was left at the end of the procedure. Results: All stones were completely fragmented and flushed into the small bowel under direct vision except for one patient in whom the procedure was aborted. In 18 patients, 1 session sufficed, and in 3 patients, 2 sessions were needed. In 7 patients, balloon dilatation was performed for benign stricture after Whipple operation (n = 3), for choledochalenteric anastomosis (n = 3), and for recurrent cholangitis (n = 1). Adjunctive 'balloon push' (n = 4) and 'rendezvous' (n = 1) procedures were needed to completely clean the biliary tree. None of these patients needed surgery. Conclusion: Complicated or large biliary calculi can be treated successfully using PTBL. We suggest that this approach should become the first choice of treatment before laparoscopic or open surgery is considered.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Differences in toxicity of anionic and cationic PAMAM and PPI dendrimers in zebrafish embryos and cancer cell lines

Dendrimers are an emerging class of polymeric nanoparticles with beneficial biomedical applications like early diagnostics, in vitro gene transfection or controlled drug delivery. However, the potential toxic impact of exposure on human health or the environment is often inadequately defined. Thus, polyamidoamine (PAMAM) dendrimers of generations G3.0, 3.5, 4.0, 4.5 and 5.0 and polypropylenimine (PPI) dendrimers G3.0, 4.0 and 5.0 were tested in zebrafish embryos for 96 h and human cancer cell lines for 24 h, to assess and compare developmental in vivo toxicity with cytotoxicity. The zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time, with EC50 values ranging from 0.16 to just below 1.7 μM at 24 and 48 hpf. The predominant effects were mortality, plus reduced heartbeat and blood circulation for PPI dendrimers. Apoptosis in the embryos increased in line with the general toxicity concentration-dependently. Hatch and dechorionation of the embryos increased the toxicity, suggesting a protective role of the chorion. Lower generation dendrimers were more toxic in the embryos whereas the toxicity in the HepG2 and DU145 cell lines increased with increasing generation of cationic PAMAMs and PPI dendrimers. HepG2 were less sensitive than DU145 cells, with IC50 values ≥ 402 μM (PAMAMs) and ≤ 240 μM (PPIs) for HepG2 and ≤ 13.24 μM (PAMAMs) and ≤ 12.84 μM (PPIs) for DU145. Neither in fish embryos nor cells toxicity thresholds were determinable for anionic PAMAM G3.5 and G4.5. The study demonstrated that the cytotoxicity underestimated the in-vivo toxicity of the dendrimers in the fish embryos. - Highlights: • Zebrafish embryo toxicity of cationic PAMAM and PPI dendrimers increased over time. • Zebrafish embryo toxicity of cationic dendrimers did not increase with generation. • Cationic dendrimers induced apoptosis in zebrafish embryos. • Toxicity of cationic dendrimers was lower in HepG2 and DU145 than zebrafish embryos. • Anionic PAMAM dendrimers showed little to no toxicity in fish embryos and cells.

60 APPLIED LIFE SCIENCES↗

Insights on proximity effect and multiphoton induced luminescence from gold nanospheres in far field optical microscopy

Gold nanoparticles can be visualized in far-field multiphoton laser-scanning microscopy (MPM) based on the phenomena of multiphoton induced luminescence (MIL). This is of interest for biomedical applications, e.g., for cancer diagnostics, as MPM allows for working in the near-infrared (NIR) optical window of tissue. It is well known that the aggregation of particles causes a redshift of the plasmon resonance, but its implications for MIL applying far-field MPM should be further exploited. Here, we explore MIL from 10 nm gold nanospheres that are chemically deposited on glass substrates in controlled coverage gradients using MPM operating in NIR range. The substrates enable studies of MIL as a function of inter-particle distance and clustering. It was shown that MIL was only detected from areas on the substrates where the particle spacing was less than one particle diameter, or where the particles have aggregated. The results are interpreted in the context that the underlying physical phenomenon of MIL is a sequential two-photon absorption process, where the first event is driven by the plasmon resonance. It is evident that gold nanospheres in this size range have to be closely spaced or clustered to exhibit detectable MIL using far-field MPM operating in the NIR region.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Phase-contrast enhanced mammography: A new diagnostic tool for breast imaging

Phase contrast and scattering-based X-ray imaging can potentially revolutionize the radiological approach to breast imaging by providing additional and complementary information to conventional, absorption-based methods. We investigated native, non-fixed whole breast samples using a grating interferometer with an X-ray tube-based configuration. Our approach simultaneously recorded absorption, differential phase contrast and small-angle scattering signals. The results show that this novel technique - combined with a dedicated image fusion algorithm - has the potential to deliver enhanced breast imaging with complementary information for an improved diagnostic process.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Radiation Exposure in Nonvascular Fluoroscopy-Guided Interventional Procedures

Purpose: To investigate the radiation exposure in non-vascular fluoroscopy guided interventions and to search strategies for dose reduction. Materials and Methods: Dose area product (DAP) of 638 consecutive non-vascular interventional procedures of one year were analyzed with respect to different types of interventions; gastrointestinal tract, biliary interventions, embolizations of tumors and hemorrhage. Data was analyzed with special focus on the fluoroscopy doses and frame doses. The third quartiles (Q3) of fluoroscopy dose values were defined in order to set a reference value for our in-hospital practice. Results: Mean fluoroscopy times of gastrostomy, jejunostomy, right and left sided percutaneous biliary drainage, chemoembolization of the liver and embolization due to various hemorrhages were 5.9, 8.6, 13.5, 16.6, 17.4 and 25.2 min, respectively. The respective Q3 total DAP were 52.9, 73.3, 155.1, 308.4, 428.6 and 529.3 Gy*cm{sup 2}. Overall, around 66% of the total DAP originated from the radiographic frames with only 34% of the total DAP applied by fluoroscopy (P < 0.001). The investigators experience had no significant impact on the total DAP applied, most likely since there was no stratification to intervention-complexity. Conclusion: To establish Diagnostic Reference Levels (DRLs), there is a need to establish a registry of radiation dose data for the most commonly performed procedures. Documentation of interventional procedures by fluoroscopy 'grabbing' has the potential to considerably reduce radiation dose applied and should be used instead of radiographic frames whenever possible.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Sci-Fri AM: MRI and Diagnostic Imaging - 05: Comparison of Input Function Measurements from DCE and MOLLI

Dynamic contrast-enhanced (DCE)-MRI is a technique for obtaining tissue hemodynamic information (e.g. tumours). Despite widespread clinical application of DCE-MRI, the technique suffers from a lack of standardization and accuracy, especially with respect to the concentration-versus-time of gadolinium (Gd) in feeding arteries (the input function, IF). MR phase has a linear quantitative relationship with Gd concentration ([Gd]), making it ideal for measuring the first-pass of the IF, but is not considered accurate in the steady-state washout. Modified Look-Locker Inversion Recovery (MOLLI) is a fast and accurate method to measure T1 and has been validated to quantify typical [Gd] ranges experienced in the washout of the IF. Two different methods to measure the IF for DCE-MRI were compared: 1) conventional phase-versus-time (“Phase-only”) and 2) phase-versus-time combined with pre- and post-DCE MOLLI T1 measurements (“Phase+MOLLI”). The IF obtained from Phase+MOLLI was calculated from MOLLI T1 values and known relaxivity, then added to the Phase-only acquisition with the washout IF subtracted. A significant difference was observed between IF values for [Gd] between the Phase-only and Phase+MOLLI acquisitions (P = 0.03). To ensure the IFs from MOLLI T1s were accurate, it was compared to [Gd] obtained from “gold-standard” inversion recovery (IR). MOLLI showed excellent agreement with IR when imaged in static phantoms (r{sup 2} = 0.997, P = 0.001). The Phase+MOLLI IF was more accurate than the Phase-only IF in measuring the washout. The Phase+MOLLI acquisition may therefore provide a DCE-MRI reference standard that could lead to better clinical diagnoses.

60 APPLIED LIFE SCIENCES↗

In the Lead Again Horizontal-Ellipsis [Journal of Cardiovascular and Interventional Radiology]

The 2013 ISI journal rankings are out and it is my pleasure to inform our readership that CVIR ranks 43/120 (2012: 46/118) journals in the field of radiology. The 2013 impact factor further improved to 2.138 (2012: 2.093). This means that Cardiovascular and Interventional Radiology again continues to be the highest ranked journal dedicated to the field of interventional radiology in 2013.This is mainly due to the great support we achieve by you as authors and readers of CVIR, your dedication to the profession, and your loyalty both to the journal and to CIRSE. For all of this, we owe you our thanks and respect.

62 RADIOLOGY AND NUCLEAR MEDICINE↗