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Fusco S.,ETH Zurich | Sakar M.S.,ETH Zurich | Kennedy S.,Wyss Institute for Biologically Inspired Engineering | Peters C.,ETH Zurich | And 8 more authors.
Advanced Materials | Year: 2014

The presented microrobotic platform combines together the advantages of self-folding NIR light sensitive polymer bilayers, magnetic alginate microbeads, and a 3D manipulation system, to propose a solution for targeted, on-demand drug and cell delivery. First feasibility studies are presented together with the potential of the full design. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Pirela S.V.,Center for Nanotechnology and Nanotoxicology | Pyrgiotakis G.,Center for Nanotechnology and Nanotoxicology | Bello D.,University of Massachusetts Lowell | Thomas T.,U.S. Consumer Product Safety Commission | And 2 more authors.
Inhalation Toxicology | Year: 2014

An association between laser printer use and emissions of particulate matter (PM), ozone and volatile organic compounds has been reported in recent studies. However, the detailed physico-chemical, morphological and toxicological characterization of these printer-emitted particles (PEPs) and possible incorporation of engineered nanomaterials into toner formulations remain largely unknown. In this study, a printer exposure generation system suitable for the physico-chemical, morphological, and toxicological characterization of PEPs was developed and used to assess the properties of PEPs from the use of commercially available laser printers. The system consists of a glovebox type environmental chamber for uninterrupted printer operation, real-time and time-integrated particle sampling instrumentation for the size fractionation and sampling of PEPs and an exposure chamber for inhalation toxicological studies. Eleven commonly used laser printers were evaluated and ranked based on their PM emission profiles. Results show PM peak emissions are brand independent and varied between 3000 to 1300000particles/cm3, with modal diameters ranging from 49 to 208nm, with the majority of PEPs in the nanoscale (<100nm) size. Furthermore, it was shown that PEPs can be affected by certain operational parameters and printing conditions. The release of nanoscale particles from a nano-enabled product (printer toner) raises questions about health implications to users. The presented PEGS platform will help in assessing the toxicological profile of PEPs and the link to the physico-chemical and morphological properties of emitted PM and toner formulations. © 2014 Informa Healthcare USA, Inc. Source

Pal A.K.,University of Massachusetts Lowell | Bello D.,University of Massachusetts Lowell | Cohen J.,Center for Nanotechnology and Nanotoxicology | Demokritou P.,Center for Nanotechnology and Nanotoxicology
Nanotoxicology | Year: 2015

In vitro high throughput screening platforms based on mechanistic injury pathways are been used for hazard assessment of engineered nanomaterials (ENM). Toxicity screening and other in vitro nanotoxicology assessment efforts in essence compare and rank nanomaterials relative to each other. We hypothesize that this ranking of ENM is susceptible to dispersion and dosimetry protocols, which continue to be poorly standardized. Our objective was to quantitate the impact of dosimetry on toxicity ranking of ENM. A set of eight well-characterized and diverse low aspect ratio ENMs, were utilized. The recently developed in vitro dosimetry platform at Harvard, which includes preparation of fairly monodispersed suspensions, measurement of the effective density of formed agglomerates in culture media and fate and transport modeling was used for calculating the effective dose delivered to cells as a function of time. Changes in the dose–response relationships between the administered and delivered dose were investigated with two representative endpoints, cell viability and IL-8 production, in the human monocytic THP-1 cells. The slopes of administered/delivered dose–response relationships changed 1:4.94 times and were ENM-dependent. The overall relative ranking of ENM intrinsic toxicity also changed considerably, matching notably better the in vivo inflammation data (R2 = 0.97 versus 0.64). This standardized dispersion and dosimetry methodology presented here is generalizable to low aspect ratio ENMs. Our findings further reinforce the need to reanalyze and reinterpret in vitro ENM hazard ranking data published in the nanotoxicology literature in the light of dispersion and dosimetry considerations (or lack thereof) and to adopt these protocols in future in vitro nanotoxicology testing. © 2015 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted Source

Cohen J.M.,Center for Nanotechnology and Nanotoxicology | Teeguarden J.G.,Pacific Northwest National Laboratory | Demokritou P.,Center for Nanotechnology and Nanotoxicology
Particle and Fibre Toxicology | Year: 2014

Background: There is a great need for screening tools capable of rapidly assessing nanomaterial toxicity. One impediment to the development of reliable in vitro screening methods is the need for accurate measures of cellular dose. We present here a methodology that enables accurate determination of delivered to cell dose metrics. This methodology includes (1) standardization of engineered nanomaterial (ENM) suspension preparation; (2) measurement of ENM characteristics controlling delivery to cells in culture; and (3) calculation of delivered dose as a function of exposure time using the ISDD model. The approach is validated against experimentally measured doses, and simplified analytical expressions for the delivered dose (Relevant In Vitro Dose (RID)f function) are derived for 20 ENMs. These functions can be used by nanotoxicologists to accurately calculate the total mass (RIDM), surface area (RIDSA), or particle number (RIDN) delivered to cells as a function of exposure time.Results: The proposed methodology was used to derive the effective density, agglomerate diameter and RID functions for 17 industrially-relevant metal and metal oxide ENMs, two carbonaceous nanoparticles, and non-agglomerating gold nanospheres, for two well plate configurations (96 and 384 well plates). For agglomerating ENMs, the measured effective density was on average 60% below the material density. We report great variability in delivered dose metrics, with some materials depositing within 24 hours while others require over 100 hours for delivery to cells. A neutron-activated tracer particle system was employed to validate the proposed in vitro dosimetry methodology for a number of ENMs (measured delivered to cell dose within 9% of estimated).Conclusions: Our findings confirm and extend experimental and computational evidence that agglomerate characteristics affect the dose delivered to cells. Therefore measurement of these characteristics is critical for effective use of in vitro systems for nanotoxicology. The mixed experimental/computational approach to cellular dosimetry proposed and validated here can be used by nanotoxicologists to accurately calculate the delivered to cell dose metrics for various ENMs and in vitro conditions as a function of exposure time. The RID functions and characterization data for widely used ENMs presented here can together be used by experimentalists to design and interpret toxicity studies. © 2014 Cohen et al.; licensee BioMed Central Ltd. Source

Deloid G.,Center for Nanotechnology and Nanotoxicology | Cohen J.M.,Center for Nanotechnology and Nanotoxicology | Darrah T.,Duke University | Derk R.,U.S. National Institute for Occupational Safety and Health | And 4 more authors.
Nature Communications | Year: 2014

The need for accurate in vitro dosimetry remains a major obstacle to the development of cost-effective toxicological screening methods for engineered nanomaterials. An important key to accurate in vitro dosimetry is the characterization of sedimentation and diffusion rates of nanoparticles suspended in culture media, which largely depend upon the effective density and diameter of formed agglomerates in suspension. Here we present a rapid and inexpensive method for accurately measuring the effective density of nano-agglomerates in suspension. This novel method is based on the volume of the pellet obtained by benchtop centrifugation of nanomaterial suspensions in a packed cell volume tube, and is validated against gold-standard analytical ultracentrifugation data. This simple and cost-effective method allows nanotoxicologists to correctly model nanoparticle transport, and thus attain accurate dosimetry in cell culture systems, which will greatly advance the development of reliable and efficient methods for toxicological testing and investigation of nano-bio interactions in vitro. © 2014 Macmillan Publishers Limited. All rights reserved. Source

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