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State-of-the-art FluidFM: force-controlled nanoscale liquid manipulation system to interact with cells at their natural length-scale in 3D

English title State-of-the-art FluidFM: force-controlled nanoscale liquid manipulation system to interact with cells at their natural length-scale in 3D
Applicant Vörös Janos
Number 164023
Funding scheme R'EQUIP
Research institution Institut für Biomedizinische Technik Universität Zürich und ETHZ
Institution of higher education ETH Zurich - ETHZ
Main discipline Other disciplines of Engineering Sciences
Start/End 01.01.2016 - 31.12.2016
Approved amount 95'000.00
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All Disciplines (5)

Discipline
Other disciplines of Engineering Sciences
Electrical Engineering
Biophysics
Mechanical Engineering
Chemical Engineering

Keywords (8)

AFM; compartmentalization; neuron network; SICM; single cell perturbation; 3D printing; local electrochemistry; FluidFM

Lay Summary (Italian)

Lead
Il FluidFM è assimilabile a una pipetta con controllo di forza che pertanto permette un posizionamento della stessa in modo accurato e delicato sopra una superficie o una cellula. In questo progetto proponiamo di acquisire una versione aggiornata del FluidFM con le seguenti caratteristiche: A) posizionamento tridimensionale a circuito chiuso in un volume di 20 × 10 × 5 cm3 con una precisione di 1 nm in z e di 10 nm in x-y; B) compatibilità con le placche multiwell 6, 12 and 24; C) regolazione della distanza punta-superficie avvalendosi di una combinazione arbitraria di due segnali come segnale di riferimento per il circuito di controllo; D) precisa modulazione dell’oscillazione del cantilever. Grazie a tali vantaggi, potremo realizzare esperimenti originali di neuroscienza, biologia cellulare e scienza dei materiali, anche in collaborazione con professori di varie università svizzere.
Lay summary

Il FluidFM e’una pipetta dotata di controllo di forza che permette di realizzare esperimentimai tentati prima in diversi campi spazianti dalla funzionalizzazionebiochimica locale di superfici alla perturbazione di singole cellule.

Terminate con successole indispensabili prove di principio, stiamo ora indagando originali questioniscientifiche pertinenti alle aree di neuroscienza, biologia cellulare e scienzadei materiali.

Ciononostante,gli esperimenti quotidiani sono ostacolati dalle limitazioni dei nostristrumenti attuali. Pertanto, vorremmo acquisire un nuovo sistema aggiornatocomposto dal modello FluidFM Bot montato su un microscopio ottico Zeiss AxioObserver Z1 e azionato dall’elettronica SPECS Nanonis. Rispetto alle nostremachine attuali, i nuovi e decisivi tratti distintivi sono i seguenti:

            posizionamento tridimensionale acircuito chiuso in un volume di 20 × 10 × 5 cm3 con una precisionedi 1 nm in z e di 10 nm in x-y;

            compatibilità con le placchemultiwell 6, 12 and 24;

            regolazione della distanzapunta-superficie avvalendosi di una combinazione arbitraria di due segnali comesegnale di riferimento per il circuito di controllo;

            precisa modulazionedell’oscillazione del cantilever.

Sfruttandoqueste migliorie, saremo in grado per esempio di connettere neuroni estraendodegli assoni dal corpo cellulare, di ottenere immagini topografiche di grandicellule senza danneggiarle in modo non-contatto, di realizzare delle curve dosein funzione della distanza su una posizione precisa della membrana cellulare,di stampare opportune microstrutture rilevanti per le loro proprietà meccanichee magnetiche.

Il nuovo sistemamigliorerà l’accesso dello strumento stesso favorendo l’intensificazione dicollaborazioni con professori dell’ETH e delle università svizzere.


 
Direct link to Lay Summary Last update: 23.11.2015

Responsible applicant and co-applicants

Publications

Publication
Additive Manufacturing of Metal Structures at the Micrometer Scale.
Hirt Luca, Reiser Alain, Spolenak Ralph, Zambelli Tomaso (2017), Additive Manufacturing of Metal Structures at the Micrometer Scale., in Advanced materials (Deerfield Beach, Fla.), x-x.
Cell Adhesion on Dynamic Supramolecular Surfaces Probed by Fluid Force Microscopy-Based Single-Cell Force Spectroscopy.
Sankaran Shrikrishnan, Jaatinen Leena, Brinkmann Jenny, Zambelli Tomaso, Vörös Janos, Jonkheijm Pascal (2017), Cell Adhesion on Dynamic Supramolecular Surfaces Probed by Fluid Force Microscopy-Based Single-Cell Force Spectroscopy., in ACS nano, x-x.
Controlled single-cell deposition and patterning by highly flexible hollow cantilevers.
Martinez Vincent, Forró Csaba, Weydert Serge, Aebersold Mathias J, Dermutz Harald, Guillaume-Gentil Orane, Zambelli Tomaso, Vörös János, Demkó László (2016), Controlled single-cell deposition and patterning by highly flexible hollow cantilevers., in Lab on a chip, 16(9), 1663-74.
Quantifying the effect of electric current on cell adhesion studied by single-cell force spectroscopy.
Jaatinen Leena, Young Eleanore, Hyttinen Jari, Vörös János, Zambelli Tomaso, Demkó László (2016), Quantifying the effect of electric current on cell adhesion studied by single-cell force spectroscopy., in Biointerphases, 11(1), 011004-011004.
Serial weighting of micro-objects with resonant microchanneled cantilevers.
Ossola Dario, Dörig Pablo, Vörös János, Zambelli Tomaso, Vassalli Massimo (2016), Serial weighting of micro-objects with resonant microchanneled cantilevers., in Nanotechnology, 27(41), 415502-415502.
Template-Free 3D Microprinting of Metals Using a Force-Controlled Nanopipette for Layer-by-Layer Electrodeposition.
Hirt Luca, Ihle Stephan, Pan Zhijian, Dorwling-Carter Livie, Reiser Alain, Wheeler Jeffrey M, Spolenak Ralph, Vörös János, Zambelli Tomaso (2016), Template-Free 3D Microprinting of Metals Using a Force-Controlled Nanopipette for Layer-by-Layer Electrodeposition., in Advanced materials (Deerfield Beach, Fla.), 28(12), 2311-5.
Tunable Single-Cell Extraction for Molecular Analyses.
Guillaume-Gentil Orane, Grindberg Rashel V, Kooger Romain, Dorwling-Carter Livie, Martinez Vincent, Ossola Dario, Pilhofer Martin, Zambelli Tomaso, Vorholt Julia A (2016), Tunable Single-Cell Extraction for Molecular Analyses., in Cell, 166(2), 506-16.

Collaboration

Group / person Country
Types of collaboration
Prof. A. Studart / ETHZ (D-MATL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. R. Spolenak / ETHZ (D-MATL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. P. Gambardella / ETHZ (D-MATL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Dr. M. Ehrbar / UniZH (Unispital) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. G. Schertler / PSI Villingen Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. J. Vorholt / ETHZ (D-BIOL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. H. Abriel / UniBE (DKF) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. L. Isa / ETHZ (D-MATL) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Dr. M. Folcher (ETHZ D-BSSE) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media "FluidFM" Micro Metal 3D Printing Firm Spun Off by ETH Zurich 3D printing industry International 2016

Associated projects

Number Title Start Funding scheme
170763 Aquisition of a state-of-the-art confocal laser scanning microscope for quantitative fluorescence studies in the area of biointerfaces science 01.09.2017 R'EQUIP

Abstract

The FluidFM is a force-controlled nanopipette enabling unprecedented experiments in different fields from local biochemical surface functionalization to single-cell perturbation. It was developed at LBB where we have carried out promising proof of principle experiments.As next step stimulated by the unique features of the FluidFM, we are now investigating original scientific questions in the following areas:•fabrication of small neuron networks with defined topology (SNF);•imaging of cardiomyocytes and perturbation at precise positions (NCCR);•electrochemical 3D microprinting (ETH).Nonetheless, the corresponding daily experiments are currently hindered by the technical limitations of our present systems (e.g., too short z range, no closed-loop positioning, custom and slow LabView routines coordinating different controllers).Therefore, we are asking for an updated system composed of the FluidFM Bot model mounted on Zeiss Axio Observer Z1 and controlled by SPECS Nanonis electronics with the OC4 oscillation module. In comparison to our present machines, the new, decisive features are:•3D close-loop positioning in a 20 × 10 × 5 cm3 volume with a precision of 1 nm in z and 10 nm in x-y;•compatibility with 6, 12 and 24 multiwell plates;•regulation of the tip-surface separation using an arbitrary combination of two signals as setpoint for the regulation loop;•extremely precise tuning of the oscillation of the cantilever in dynamic mode.Taking advantage of these improvements, we will be then e.g. able to connect neurons pulling out axons from their cell bodies (thanks to the closed-loop positioning), to safely image larger cell in non-contact mode (thanks to the extended z-range), to perform dose vs. distance curves at a precise location on a cell (thanks to the combination of both), and to print ad hoc submicron structures relevant for their mechanical and magnetic properties.The new system will also improve instrument access allowing the intensification of collaborations with external users. We are in active contact with professors from ETH and Swiss universities for novel experiments for:•the manipulation of single cells (bacteria as well as primary cells like cardiomyocytes and stem cells);•the inspection of extrusion processes of composite inks from a nanonozzle;•the investigation of mechanical and magnetic properties of microstructures.
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