Ongoing projects NanoSafety and NanoMedicine
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Microfluidic platform for real-life exposure to nanomaterials
The microscopy setup consists of a BioStation IM (Nikon) with automated XYZ stage, temperature and CO2 control for incubation of living cells. Impedance is monitored in real-time with a LCR meter (HIOKI). The platform is equipped with a OB1 MK4 pressure flow controller (Elveflow). Microfluidic chips and Au-microelectrode arrays are designed and made in-house at the clean-room facilities of the Dept. of Physics and Technology (UiB).
Multiplexed microfluidic platform for label-free, real-time electrical impedance spectroscopy (EIS) and live-cell imaging of cells exposed to nanomaterials.
The microscopy setup consists of a fluorescence microscope (Olympus) with automated XYZ stage (Prior Scientific), Andor’s differential spinning disk (DSD) unit with CMOS camera for semi-confocal image acquisition (Oxford Instruments). The microscope is enclosed in an environmental chamber with temperature, humidity and CO2/O2 control for incubation of living cells. EIS instrumentation consists of an Autolab PGSTAT potentiostat (Metrohm) with multiplexing module (up to 16 channels) or 64-channel ISX3 impedance analyser (Sciospec). The platform is equipped with pulsation-free syringe pumps (CETONI), high-precision peristaltic pumps (CETONI) and OB1 MK4 pressure flow controller (Elveflow). Microfluidic chips and Au-microelectrode arrays are designed and made in-house at the clean-room facilities of the Dept. of Physics and Technology (UiB).
Microfluidic set-up. A) Schematic diagram depicting the components of the microfluidic platform. B) Different designs of interdigitated MEAs used. C) Multiplexed microfluidic chip made in polydimethylsiloxane with Au-microelectrode arrays.
A549 lung cancer cells exposed to multi-layered graphene encapsulated magnetic nanoparticles (GEMNS) for 2h at a flow rate of 1ul/min. A) Impedimetric analysis at 25KHz AC frequency. B) Fold-change relative to control 2 and 22h after treatment. C) Brightfield images 22h after exposure.
Researcher: Ivan Rios-Mondragon, PhD, PI: Mihaela Roxana Cimpan, Professor
3D biological models
Advanced in-vitro models to study the interaction of nanomaterials with biological systems
We develop organ-on-a-chip models to understand how nanomaterials interact with biological systems. We develop symplistic, but reliable models to limit/replace the use of animals for testing of nanomaterials present in consumer products and medical devices including nanopharmaceuticals.
Microvasculature on-a-chip model. A) Schematic of the 3D vascular model. Microvascular networks are formed when endothelial cells are co-cultured with fibroblast within a fibrin gel inside the microfluidic chip made of PDMS. The lumen of the blood vessels is accessible for delivery of NMs. B) Microfabricated Si-mold and its replica in PDMS containing the microfluidic network. C) Brightfield micrograph showing the formation of vascular networks of HULEC-5a co-cultured for 7 days with primary lung fibroblasts. D) Immunostained co-cultures. HULEC-5a formed tubular networks.
Breast cancer-on-a-chip model for testing of nanomaterials
Microfluidic chip for breast cancer-on-a-chip model. Cartoon depicting the different components and cells integrating the breast cancer-on-a-chip model (top-left). Microfluidic chip (bottom-left). 3D reconstruction of HUVEC microvasculature and adjacent MFC10a cancer cell monolayter in the breast cancer chip (right). Empty liposome (Lip-SiR) were perfused in the HUVEC channel for 24 hr. For both cell lines the nucleus is shown in blue (DAPI), membrane in magenta (WGA-AF488) and empty liposome in green (Lip-SiR). Top, merged channels DAPI/WGA-AF488/Lip-SiR. Middle, merged channels DAPI/Lip-SiR. Bottom, single channel for Lip-SiR. White arrows indicate Lip-SiR signal.
Lung-on-a-chip model for testing of nanomaterials
A) master moulds and replicas in polydimethylsiloxane (PDMS) of top (air) and bottom (liquid) chambers that compose the lung-on-a-chip model. Master moulds were fabricated using photolithography. B) Side view (top) and magnification (bottom) of the fully assembled chip. The air and liquid chambers are interfaced by a thin (20 um) PET microporous membrane comprising 3 um pores.
Researcher: Ivan Rios-Mondragon, PhD, PI: Mihaela Roxana Cimpan, Professor
Label-free impedance-based and electrochemical methods
Impedance-based high throughput nanotoxicity screening on adherent and single cells.
Label-free: Impedance based biosensor technology does not require markers or dyes. Interference-free from Nanomaterials and Nanoparticles perturbation.
xCELLigence system (Agylent Technologies, Inc., USA)
Real-time kinetic readouts: Obtains data continuously from seconds to days. Simultaneously monitor up to three plates, without scheduling conflicts. Easy workflow: Plate cells, expose to Nanomaterials and begin monitoring.
Measures cell number, size, morphology, and attachment properties, with the ability to perform kinetic analysis of cell invasion/migration (CIM).
AmphaZ30 (Amphasys AG, Lucerne, Switzerland)
Amphaz30 is an impedance flow cytometer for high-throughput single-cell characterization without optical components. Single cells pass through a micrometer-sized channel in a chip equipped with microelectrodes. The electrical impedance changes when a cell passes through the applied alternating current (AC) field, permitting cell detection and impedance measurement. The measured impedance is used to assess cellular size, membrane capacitance, and cytoplasm resistance and to differentiate between live and cell cells and modes of cell death.
Cyclic voltammetry for oxidative stress testing.
We use cyclic voltammetry (CV) to study if nanomaterials may cause oxidative stress in biological systems. The total antioxidant capacity (TAC) of a biofluid reflects the amount of antioxidants available to counteract oxidative stress.
Module for measurement of transepithelial/endothelial electrical resistance (TEER)
Top, TEER module placed on top of the lung-on-a-chip and hook up to the wires at the microscope stage. Bottom, magnification showing the gold-plated electrodes that are immersed in the cell culture medium at the inlets/outlets of each cell culture chamber of the lung-on-a-chip
Researcher: Ivan Rios-Mondragon, PhD, PI: Mihaela Roxana Cimpan, Professor
HORIZON2020 EU Project "RiskGone"
RiskGONE PROJECT – Science-based Risk Governance of Nano-Technology (nilu.no)
WP5 co-lead and PI: Mihaela Roxana Cimpan, Professor; Researcher: Ivan Rios-Mondragon, PhD; Ying Xue, PhD; Håkon Van Ta, MSc Nano; Arnaud Lemelle, PhD; Anne Marthe Drønen, BSc
NANO2021 RCN project "NanoBioreal"
Research School for Training the Next Generation of Micro- and Nanotechnology Researchers in Norway (TNNN)
WP leader and Board member: Mihaela Roxana Cimpan, Professor
EEA Project "TEPCAN"
WP leader, PI: Mihaela Roxana Cimpan, Professor; Researcher: Ivan Rios-Mondragon, PhD
ANR project "NanoMilk"
WP leader, PI: Mihaela Roxana Cimpan, Professor; Coordinator: Anne Burtey, PhD (INRAE, Paris); Researcher: Ivan Rios-Mondragon, PhD; Marie Simon, PhD cand (INRAE, Paris).
Use of nanomaterials: Perception and hazard
https://www.uib.no/en/rg/oralhealth/152931/use-nanomaterials-perception-...
PI: Anne Nordrehaug Åstrøm, Professor; Victoria Xenaki, PhD cand.; Mihaela R.Cimpan, Professor Mihaela Cuida Marthinussen, Associate Professor; Daniela E. Costea, Professor; Stein Atle Lie, Professor.
UH-nett Vest Project: New methods for assessing the effects of nanomaterials, MRI and various stressors on cells
https://uhnettvest.no/finner-nye-metoder-for-a-kartlegge-biologiske-effe...
Mihaela Roxana Cimpan, Ivan Rios-Mondragon, Kamal Mustafa (IKO), Emil Cimpan, Alvhild Alette Bjørkum (HVL), Bodil Holst, Martin Greve (IFT), Beate Kluge og Karen Rosendahl (Haukeland University Hospital)
Effects of Artificial Saliva on Silica nanoparticles
Students: Ida Marlene Nygård and Caroline Skjennum
Supervisors: Asgeir Bårdsen, Professor; Mihaela R. Cimpan, Professor
Senior engineer: Hanzhen Wen
Effects of Nanodiamond particles
Nanodiamond particles and stem cells.
Nanodiamond particles: Osteogenicity and safety aspects
Mohammed A. Yassin, Associate Professor; Mohammed Ibrahim, PhD; Mihaela R.Cimpan, Professor, Kamal Mustafa, Professor, Julia Schoelermann, PhD.
