Nimic Final report by Cok Francken

NIMIC NANO

IMAGIN G N

U N DE R L

I N D U STRI AL R

C O N D IT IONS O

SM A R T M I X P R O G R A M 2007-2013 • PR O J E C T C O D E : SSM06002

20nm

Preface

With great pride and pleasure we present this booklet, which summarizes the results of the public-private research program on Nano-Imaging under Industrial Conditions, in short NIMIC. This booklet also serves as the final report of this SmartMix program for the funding agency Agentschap NL. The financial report will be presented

Colophon

separately. Editors & text:

NIMIC is at the basis of a series of highly rewarding developments of novel ultra-mi-

Joost Frenken Cover TEM-photo:

croscopy technology and their application to three areas of interest with high

This is a copper naoparticle heated to

relevance for society, namely catalysis, bio-medical mechanisms, and high-tech

Contributions by:

150°C in 50 mbar O2. It is hollow due

materials. The NIMIC challenge has been to enable and perform live atomic- and

Henny Zandbergen,

to the nanoscale kirkendall effect. This

molecular-scale observations of relevant processes under the harsh conditions that

Bram Koster,

effect may be used to regenerate a

are realistic for each of these three subject areas.

Bart Nelissen,

catalyst.

Gerard van Veen

Picture by: Dr. Søren Vendelbo

Richard van der Linde

The success of NIMIC has been possible only by virtue of the intimate collaboration between the public and private partners in the NIMIC consortium. These NIMIC ties

Results made possible by:

Graphic Design:

will remain present and active for many years to come and already now are seen to

Pleun Dona,

Cok Francken | NewMedia Centre

act as the launching pad for a multitude of follow-up activities. The present report documents this catalyzing role of NIMI C and should also be regarded as a strong

Fredrik Creemer,

plea for stimulating public-private funding schemes of the SmartMix type.

Gertjan van Baarle,

Photography:

Patricia Kooyman,

Arthur Vahlenkamp

Tjerk Oosterkamp,

Vahlenkamp Fotografie

30 June, 2013

Peter Peters,

Printed by:

Joost Frenken, Scientific Director of NIMIC

Marcel Rost, Frans Tichelaar

Mart.Spruijt bv

Richard van der Linde, Business Director of NIMIC

Stig Helveg,

N I M I C Final Report | Colophon | Preface

Contents Preface

General results of the programme

Scientific Results of N I MI C

2.1 Theme 1: Live nano-imaging of processes under catalytic conditions

2.2 Theme 2: Live nano-imaging of processes under biological and bio-medical conditions

2.3 Theme 3: Live nano-imaging of materials processes

Indicators & deliverables

National and international visibility of NIMIC

Organization & governance

5.1 Governance and operation

5.2 Special taskforces and impulses

5.3 Strategic Advisory Committee

5.4 Annual financial checks

5.5 After-N I M I C period

Appendix A,

Appendix A1 Peer reviewed Journal publications

Appendix A2 Peer reviewed Conference publications

Appendix A3 Other publications

Appendix A4 Filed patents

Appendix A5 N I M I C PhD students en postdocs

Appendix A6 PhDs theses

Appendix B,

Deliverables

Appendix C,

Composition of NIMIC

N I M I C Output

NIMIC Final Report | Contents

Prof.dr. Joost Frenken (Leiden University), Leader of the high-pressure and high-speed Scanning Probe Microscopy projects 1.1 and 4.3 and Scientific Director NIMIC

Results of the NIMIC programme |

Chapter 2 | Scientific results and value creation

General results of the programme Introduction NIMIC, i.e. Nano-Imaging under Industrial Conditions, has been one of the seven SmartMix programs that have been granted in 2007. The goal of NIMIC has been to use electron microscopy and scanning probe microscopy techniques to make physical, chemical and biological processes visible that are taking place on the atomic and molecular scale. Novel technologies have been developed to deliver the first, direct ‘atomic look’ on highly relevant,

Henri van Luenen,

practical phenomena under realistic and relevant process conditions.

Institute manager NKI-AvL Through NIMIC we have been able to study cellular migration

NI M I C has been a six-year program that has run from 1 July,

NIMIC results

through narrow constrictions,

2007, to 1 July, 2013. The N I M I C consortium consisted of the

Three thematic areas were defined as the focus for the live

which was not possible before.

following eight partners from the public and private domains:

nano-imaging of NIMIC establishing a strong match between the

This will help us understand an

Delft University of Technology (administrative seat of NIMIC),

scientific expertise of the consortium partners and three of the

important process in the disease

Leiden University, FEI Company BV, Leiden Probe Microscopy

current Dutch Top Sectors (Chemistry, Life Science, and High-Tech

cancer, namely metastasis.

BV, Albemarle Catalysts Company BV, Leiden University Medical

Systems and Materials):

Centre (LUMC), Netherlands Cancer Institute - Antoni van

–– Live nano-imaging of processes under catalytic conditions

Leeuwenhoek Hospital (NKI-AvL), and Haldor Topsøe A/S. The total

–– Live nano-imaging of processes under biological and bio-medi-

NI M I C budget of 25 M€ contained a 14 M€ grant from SmartMix and 11 M€ in in-kind and cash contributions from the individual

cal conditions –– Live nano-imaging of materials processes.

partners in the program. In order to enable nano-scale observations in each of these areas, two families of novel, advanced instrumentation have been developed within the NIMIC program. One is centered on the technique

NIMIC Final Report | Chapter 1 | General Results of the programme

MSc. Sander Roobol (Leiden University), NIMIC PhD student on the ReactorAFM project

Frank de Jong director R&D FEI The SmartMix program NIMIC has been a very successful partnership for FEI. Several research

of Transmission Electron Microscopy (TEM), the other on Scanning

The new nano-imaging tools have been employed in first series

Probe Microscopy (SPM), such as scanning tunneling microscopy

of experiments, aimed at exploring the new possibilities provided

by FEI in the framework of the

and atomic force microscopy. In both cases, these developments

by the new instruments in the context of several specific examples

program, with help of its partners,

included combinations with additional techniques, for example

(‘showcases’) and at validating the new techniques in the process

have led to subsequent (in-house)

optical (fluorescence) microscopy, and a collection of auxiliary

and demonstrating them to the research communities for each of

tools, for example for the preparation and handling of specimens.

the three thematic areas.

These instrumentation developments have been largely in the

Section 2 of this report summarizes the results obtained within the

for low-dose imaging, and a new

hands of the instrumentation driven groups at the two universities

NIMIC program and presents our showcases, e.g. with stunning,

generation of Environmental TEM

involved in NIMIC (Delft and Leiden) and the industrial suppliers

atomically-resolved movies of catalytic nanoparticles undergoing

(ETEM).

of laboratory instrumentation (FEI Company and Leiden Probe

dynamic variations in their shape, correlated with spontaneous

Microscopy), with a significant involvement of the other NIMIC

oscillations in catalytic activity, direct observations of correla-

teams, who also served to define the targets and requirements from

tions between the microscopic architectures of aortic wall tissues

the perspective of the chemical industry (Albemarle and Haldor

and the mechanical failure modes of these structures in case of

Topsøe) and that of the medical institutions (NKI-AvL and LUMC).

aneurisms and Marfan’s disease, and the atom-by-atom rearrange-

topics that have been investigated

product developments. Two products have been brought to market already: the Falcon camera

ments and thinning of narrow, conductive metal structures during Gertjan van Baarle, director LPM

the process of electromigration, one of the failure mechanisms of microelectronic circuits.

By participating in the SmartMix program NIMIC, LPM BV has been enabled to focus on the devel-

NIMIC’s value creation

opment and testing of a range of highly special-

Valorization has formed a major drive in the NIMIC program. In

ized scientific instruments and explore a variety

order to place this aspect in the foreground from the very start, three

of opportunities together with the consortium

of the four work packages, in which NIMIC was structured, were

partners. Several instruments have been brought

headed by prominent end users, from the industry or from a medical

to the market successfully, and new products are

institution. Value has been created along three different lines.

in the pipeline. NIMIC has made LPM grow from a spin-off company to a well-established supplier

First of all, important parts of the new instrumentation that has

of high-pressure surface-science instrumentation

been developed within NIMI C have been further developed into

around the globe.

products or product prototypes by commercial NIMIC partners or

NIMIC Final Report | Chapter 1 | General Results of the programme

Dr.ir. Patricia Kooyman (Delft University of Technology), Leader of Catalysis projects 1.2 and 1.3, and Indra Puspitasari (Delft University of Technology), NIMIC PhD student on high-pressure TEM and catalysis

Results of the NIMIC programme |

Chapter 2 | Scientific results and value creation

by spin-outs from NI M I C ’s academic partners. Not only do these

The value creation of NIMIC is only partly quantified by the set of

add to the product portfolio’s of these commercial enterprises

indicators and deliverables, which were agreed upon at the start of

and thus establish direct economic value, they also enable new

the program. At the moment this report went to press there were

research communities to develop that are beginning to use these

52 journal publications and 64 peer reviewed conference contribu-

instruments as their ‘toolbox’, which adds an enormous secondary

tions. Besides the products and novel instrumentation developed

value to N I M I C .

within the program, also 7 patents have been filed. NI MIC also facilitated in initiating and starting up new research facilities and

The second line of value creation has been in the generation of

new research initiatives, both Scientific (NWO) and Top-Sector

new scientific insights into phenomena with practical relevance,

related (HTSM, Chemistry and Life Science). These aspects are

such as catalysis, failure mechanisms of aortic tissue and electro-

discussed more elaborately in Chapters 3 (Indicators and delivera-

migration. Even though the emphasis within N IMIC has been on

bles) and 4 (National and international visibility).

the development and professionalization of the instrumentation and methodology, inspiring scientific breakthroughs have been realized in each of the thematic areas of N I M I C. In order to further boost the ‘return on investment’ also in this arena of scientific breakthroughs and valorization, final resources, stemming directly from the cash contributions of commercial N I MIC partners, have

Eelco Vogt

been allocated to a small number of final-stage projects that will

Director, External Technology

partly extend beyond N I M IC ’s official end date.

Albemarle Catalysts “Nobody said it would be easy, and this turned

The third line of significant value is in establishing a cohesive

out to be right. It took a huge team effort to break

community of researchers and technical staff, trained in develop-

a number of technical barriers during the NIMIC

ing and applying the new tools and tricks. This provides us with a

project. By breaking these barriers, the NIMIC

significant concentration of the full chain of expertise that is essen-

effort has provided access to experimental realms

tial in each of N I M I C ’s main thematic areas and with an excellent

that were not available to us before. We will now

basis for future development tracks in advanced instrumentation.

be able to truly look at catalysis in action!”

This N I MI C community is also a natural launching pad for future public-private collaborations, as we have been seeing reflected already by a variety of new or follow-up activities.

NIMIC Final Report | Chapter 1 | General Results of the programme

Five STM images (100 nm x 100 nm) on the same part of the Pt(110) surface at 423 K under 0.68 bar of NO and an H2 partial pressure ranging from 0.1 bar (left) to 0.64 bar (right). The images demon-

Dr. SĂ¸ren Vendelbo

strate the completely revers-

(Delft University of Technology),

ible, spectacular variation in

NIMIC Postdoc on high-pressure

the density of the NO-induced

TEM and catalysis

steps on the initially flat platinum surface.

The NIMIC way The structure of the N I M I C program has been different from most

The highly interactive nature of NIMIC combined with the struc-

Dutch research programs in that significant interdependencies

ture of frequent NIMIC meetings and visits between NIMIC part-

existed between individual projects within the program. For exam-

ners has forged a cohesive research community that bridges both

ple, experimental activities by end user teams could only start

between disciplines, i.e. the three thematic areas, and between

after instrumentation development teams had first ‘delivered’ their

public and private parties. This community will have a lifetime well

new tools. In turn, the technical specifications that the instrument

beyond the six-year duration of NIMIC. Partly supported by the

developers had to make their new tools meet were ‘dictated’ by

instrumentation resulting from the NIMIC program, it currently

the teams of end users, based on their specific, scientific targets.

forms the basis for a multitude of new research and R&D initiatives

These aspects have made N I MI C interactive and dynamic but

and activities, in which the ‘torch of NIMIC’ is being passed on.

have also introduced risks of cascading technical problems and

This makes the legacy of the NIMIC program significantly larger

project delays. The latter have required active management by the

and longer-lived than the output presented in the present report.

NI M I C Directors and Board of budgetary, IP-related and human resources within the program. This is more elaborately discussed in Chapter 5. Charlotte Clausen Appel, General manager Microscopy Haldor Topsøe The ambition at Haldor Topsøe is to maintain excellence in science and technology in heterogeneous catalysis and beyond. Understanding heterogeneous catalysis on the atomic level at real conditions is essential for the design of catalysts. NIMIC has been a step in the continuing advancement of live imaging of catalysts under reaction conditions.

NIMIC Final Report | Chapter 1 | General Results of the programme

Dr. Bart Nelissen, (Global Analytical Director at Albemarle Catalysts Company), Leader of Work Package 1 on Live NanoImaging of Processes under Catalytic Conditions

Scientific Results of NIMIC The research and development efforts in the N I M I C consortium have been devoted to three scientific and technological themes, aiming for live nanoimaging in three different areas of application: (i) catalysis, (ii) bio-medical and

(iii) material science. Each of these application areas has required significant developments in instrumentation and methodology. We have organized our work in four work packages, where the first three were directly associated with the three themes and the fourth entirely with supporting instrumentation and methodology. In this part of the report we summarize highlights from our work, loosely arranged according to the three major thematic areas.

2.1 Theme 1: Live nano-imaging of processes under catalytic conditions The target in this part of N I M I C was to develop advanced micros-

a wide range of (semi)-realistic gas flow and reaction conditions,

copy instrumentation and methods and use these for fundamental

thereby opening up a new field of catalysis research.

investigations of model catalyst systems under actual reaction conditions. In particular, we have concentrated on Scanning

Scanning Probe Microscopy instrumentation. Two scanning

Tunneling Microscopy (STM), Atomic Force Microscopy (AFM) and

probe microscopy setups have been designed, constructed and

High-Resolution Transmission Electron Microscopy (TEM).

started up at Leiden University, one Reactor-STM and one ReactorAFM. The STM provides full atomic resolution at imaging rates up

Exploratory studies had been performed already prior to NIMIC,

to two images per second at flows of reactive gas mixtures, tested

to demonstrate the feasibility of STM and TEM under modest

up to 6 bar and specimen temperatures tested up to 600 K. The

reaction conditions. Within N I M I C , these developments have been

non- contact AFM has not reached atomic resolution but it has the

brought to a professional level, introducing a new generation of

important benefit – with respect to the STM – that it can operate

instrumentation with which model catalyst surfaces and nanopar-

on non-conductive specimens, such as an oxide-supported metal

ticle ensembles can now be followed with high resolution under

catalyst.

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Dr. Stig Helveg (Senior Research Scientist at Haldor TopsĂ¸e A/S), highpressure TEM and catalysis

An essential component of both setups is a versatile system for preparing well-controlled gas mixtures with separate control over the flow rate, the mixing ratios and the total gas pressure. Combined with this is a system for rapid and sensitive detection and analysis of the composition of the gas that leaves the reactor volume. The two scanning probe instruments are controlled (electronics and software) by the Camera control system of LPM. For

Complete Reactor-STM setup

the purpose of display and analysis of simultaneously measured

(left) and the flange with

data of different types, such as STM images and partial pressures,

the development of the Environmental Transmission Electron

the high-pressure Scanning

dedicated software has been developed, called SpaceTime, which

Microscope (ETEM) by FEI, based on its extremely stable Titan

Tunneling Microscopy itself

has also been used successfully to display movies of TEM-images

platform. Aberration correctors can now be combined with in-situ

(right); both are photographs

(see below) and simultaneously measured partial pressures of

microscopy delivering 0.15 nm resolution at pressures of 20 mbar.

of the ready-to-market

reactants and reaction products.

This system has been installed in several major electron micros-

version, developed by LPM.

copy labs around the world, producing excellent scientific results. These developments have led to several products of LPM, which are now commercially available. A professionalized version of the complete Reactor-STM system, including the full vacuum system with sample preparation and handling, the gas preparation and analysis systems, and the electronics and control system, is now offered as a product package. The first complete system has been sold to and installed at Brookhaven National Laboratories (Brookhaven, NY, USA). A more compact, ‘low-budget’ system

Schematic of the surface

is under preparation at LPM. LPM is further developing the gas

micromachined nanoreactor

handling equipment into a separate system that can be used in

developed at DIMES, TUD (left)

A new TEM (FEI Titan) has been installed in the Van Leeuwenhoek

and a nanoreactor held in the tip

Laboratory of the TUD, where a major effort has been invested in

of the TEM nanoreactor holder,

Transmission Electron Microscopy instrumentation. In

the development of new generations of so-called ‘nanoreactors’.

jointly developed by FEI and TUD

parallel with the SPM instrumentation, a new generation has

These are MEMS-devices with thin, electron-transparent windows.

(right).

been developed of in-situ TEM equipment. The first step has been

They can be loaded with catalysts. Even though the nanoreactors

combination with a wide variety of other research instruments.

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Prof. dr.ir. Henny Zandbergen (Delft University of Technology), Leader of Project 2.1 and Leader of Work Package 3 on Live NanoImaging of Materials Processes

essentially are consumables, each one is provided with its own

previous ETEM experiments at Haldor Topsøe. Another challenge

heating element and temperature read-out. Gas in- and outlets

that has been dealt with successfully was in the loading of the

make it possible to flow gas mixtures through the device. The

nanoreactors with catalytic nanoparticles, which has involved

nanoreactors fit into specially developed TEM holders, with which

extensive optical microscopy characterization and has resulted

they can be maneuvered into the specimen position in the TEMs

in unconventional choices for some of the channel dimensions in

of FEI. These holders contain electrical contacts for heating and

these devices. The characterization of the nanoreactors has further

temperature measurement and carry the gas lines to connect to

focused on the calibration of the temperature and its distribution

the nanoreactor’s in- and outlets. The initial holder designs for

over the device, using electron energy loss spectroscopy (EELS)

the application to catalysis have been developed at the TUD in

measurements on H2 gas. The present generation nanoreactors

a collaboration with FEI and Haldor Topsøe. In the course of the

from the TUD is fit for temperatures up to 1075 K and gas pres-

NI M I C project two further design and construction stages have

sures up to 1 bar (H2, CO and O2). FEI has initiated a parallel devel-

followed, in both of which FEI has played a leading role, with

opment effort for bonded nanoreactors at the MEMS-company

significant input from other N I M I C partners. This has resulted in a

Lionix. This work has resulted in a first series of prototype nano

new prototype that is expected to form the basis of a commercial

reactors in the final stages of the NIMIC funding period.

product of FEI. Significant work has been invested in eliminating contamination of nanoreactors during electron-beam operation.

With our first high-pressure TEM experiments, we have estab-

This has involved the nanoreactor and holder designs and the

lished a working baseline at both TEM facilities, Haldor Topsøe

procedures for their production and handling. Stringent holder

and TU Delft, including the complete workflow from nanoreactors

tests have been carried out at FEI and Haldor Topsøe, following

and the loading of these devices, to the dedicated TEM holder, the

a test program with specifications based on experience from

gas system, including the gas analysis, the TEM operation during

Five STM images (100 nm x 100 nm) on the same part of the Pt(110) surface at 423 K under 0.68 bar of NO and an H2 partial pressure ranging from 0.1 bar (left) to 0.64 bar (right). The images demonstrate the completely reversible, spectacular variation in the density of the NO-induced steps on the initially flat platinum surface.

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Dr.ir. Maria Rudneva and Mrs. Tatiana Kozlova (Delft University of Technology), NIMIC PhD student and MSc student, respectively, both on TEM studies of electromigration

high-pressure experiments, and the synchronization of the data

to NO leads to a dramatic faceting of the Pt surface into a regularly

sources during the experiments, e.g. with SpaceTime (see above).

stepped configuration. We attribute this effect to the NO-induced compressive stress on the Pt surface, which is supported by

First scientific results. First experiments with the new SPM

Density Functional Theory (DFT) calculations. Simultaneous expo-

and TEM instruments have focused primarily on catalytic oxida-

sure to NO and H2 leads to intermediate step densities, depending

tion-reduction reactions. After test experiments, demonstrating

directly on the NO/H2 ratio. The simultaneously measured produc-

atomic resolution on Au(111), the Reactor-STM has been used to

tion rates of H2O and NH3 depend negatively on the step density,

re-address the catalytic oxidation of CO on the Pt(110) surface. For

providing us with a unique opportunity to relate structural features

the first time, the regular (surface oxide) structure that forms on

on the model catalyst surface with reaction mechanisms. First

this surface during the reaction at atmospheric pressures and high

observations of Pt(110) during reduction of NO by CO are indica-

temperatures has been imaged with STM with a resolution that

tive of a phase separation on the surface between NO-covered and

was good enough to distinguish the individual atomic rows. The

CO-covered strips, running parallel to the steps on the metal surface.

observations are in full accordance with the structures, proposed on the basis of our experiments with high-pressure surface X-ray

An important breakthrough for catalysis research has come in

diffraction at the ESRF in Grenoble. Reduction of NO both by H2

the application of nanoreactors for the direct TEM observation

and by CO has been investigated on the same surface. Exposure

of Pt nanoparticles during CO oxidation at a total pressure of 1 (left) High-resolution TEM image of a Pt nanoparticle acquired in situ during CO oxidation in a mixture of O2, CO and He at a total pressure of 1 bar and a temperature of 400°C. Scale bar 5 nm. (right) Time-resolved mass spectrometry data for the reactant CO and the product CO2 that exit the nanoreactor, together with

5nm

the temperature measured in the reactor.

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Prof.dr. Bram Koster (Leiden University Medical Center), Leader of Project 2.2 and Leader of Work Package 2 on Live Nano-Imaging of Processes under Biological and Bio-Medical Conditions

bar and a temperature of 400oC. It was demonstrated that simul-

ing of the metallic core of the particle proceeds and the simultane-

taneous high-resolution TEM images of the Pt nanoparticles and

ous accumulation of oxide on the outside.

mass spectrometry of the gas exiting in the nanoreactor could be

We have made a serious start with experiments on desulphuriza-

obtained. Such operando data has long been emphasized as a

tion of thiophene molecules with the use of MoS2 model catalyst

necessity to understand dynamic structure-activity relationships

particles. Pilot experiments in a prototype ReactorSTM setup have

in catalysis but until now such insight was only available from

shown that, once formed on a Au(111) substrate, the particles

spatially averaging techniques. In the present work it was demon-

could be imaged stably also under reaction conditions, in which

strated for the first time how dynamic changes in the surface of

they were exposed to thiophenes and H2 gas under atmospheric

the nanoparticles couples to an oscillatory behavior in the catalytic

pressures at elevated temperatures. Catalytic conversion was low

oxidation of carbon monoxide.

under these conditions and could only be detected in batch mode. Due to the extra efforts that we have had to invest in the technical

TEM experiments on Cu nanoparticles under oxidizing and reduc-

developments of the nanoreactors and the holders, there has not

ing conditions at atmospheric conditions and elevated temper-

been sufficient time left within NIMIC to launch a parallel activity

atures have resulted in the first time-resolved, live observations

to follow the reaction on MoS2 nanoparticles inside a nanoreactor

of the so-called Kirkendall effect. Under oxidizing conditions, the

with the use of high-resolution TEM. A second series of experi-

nanoparticles form an oxide shell. Outward diffusion of

ments is being prepared that will mostly take place after the official

metal through this shell is thought to proceed more easily than

closing date of NIMIC and will be carried out in the high-resolu-

inward diffusion of O2. As a result of this, the particles hollow out

tion ReactorSTM setup. The target in these extra experiments goes

spontaneously to eventually produce a hollow oxide structure.

beyond the original NIMIC deliverables and will be to visualize

When reduced, these hollow particles often separate out into

the individual reaction steps: (i) the hydrogen-induced formation

several smaller metal particles, which gives the effect practical

of a sulfur-vacancy in the edge of a MoS2 particle, (ii) the docking

relevance, since this is a method to regenerate a catalyst when it

of a sulfur-containing molecule in the vacancy, and (iii) the hydro-

has lost active area due to sintering. The TEM observations have

gen-induced cleavage of the C-S bond, leading to the desorption of

enabled us to identify the crystallographic nature of both the oxide

the de-sulphurized molecule.

shell and the metallic interior and follow in detail how the empty-

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Dr. Jan Willem Beenakker (Leiden University), NIMIC PhD student on AFM and confocal microscopy studies of the collagen network in arterial wall tissue

2.2 Theme 2: Live nano-imaging of processes under biological and bio-medical conditions The target in this part of N I M I C was to develop and apply

An alternative nanoreactor design route, based on glass, has been

advanced microscopy instrumentation and methods to address

pursued by FEI and NKI-AvL, with the microfabrication of the

biologically and bio-medically relevant questions under relevant

glass device contracted out to Lionix. The architecture of the latter

conditions. In particular, we have concentrated on High-Resolution

devices provided the possibility to directly visualize cell migration

Transmission Electron Microscopy (TEM) and Atomic Force

through a narrow constriction. This has resulted in a patent filed by

Microscopy (AFM).

FEI and NKI-AvL

TEM instrumentation. Also for the fluid environment, typical

For life science applications of TEM, the electron beam dose has

for biological specimens in their native form, the configuration

to be kept to a minimum, in order to avoid severe damaging of

of a nanoreactor in a dedicated holder provides a very attractive

the biological specimens. An important development for low-dose

means for high-resolution TEM imaging. Several nanoreactor

imaging is that of CMOS cameras for direct electron detection.

designs have been realized for this purpose at the TUD, based on

After evaluation of FEI’s prototype, the camera has been integrated

the combination of Si and SiN. Further research at the LUMC has

in an actual TEM and made available for customer testing. NIMIC

been devoted to the possibility to use these nanoreactor cells to cryo-immobilize their biological contents, for which a special setup has been constructed at LUMC. The nanoreactors have also been

The MAVIS system, developed at

developed at the TUD and evaluated at the LUMC for their use in a

the LUMC for correlative light- and

correlative-microscopy combination of Fluorescence Microscopy

electron microscopy. The philos-

(FM) and TEM. The philosophy behind such a combination is

ophy is to perform fluorescence

to employ the FM to perform live cell imaging and to identify a

microscopy of live cells and rapid

specific biological/ biomolecular event. The corresponding molec-

vitrification with this system, after

ular configuration is then rapidly vitrified by plunge freezing, after

which the vitrified specimens can

which the cold nanoreactor, with its biological structure of interest,

be subjected to three-dimensional

is inserted into the TEM for high-resolution electron tomography.

molecular imaging by cryo electron tomography.

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Prof. dr.ir. Tjerk Oosterkamp (Leiden University), Leader of Projects 2.4, 2.5 and 2.7 on advanced SPM and confocal microscopy studies of biological and biomedical systems

partners, in particular from the LUMC, were among the first to test the CMOS camera at FEI, with a particular emphasis on the low-dose performance. The results were very satisfactory and the camera is presently commercially available on FEI systems. Follow-up projects within FEI are currently in progress to develop a next-generation camera with even better performance. SPM instrumentation. Instrumentation has been developed within LU for the imaging (optical and AFM) and simultaneous mechanical indentation of biological tissues. An instrument has been constructed at LU that combines AFM imaging and force measurements with multi-photon, confocal

(left) Schematic of the multifo-

light microscopy. A special feature of the optical part of this novel

cal two-photon laser scanning

setup is that it enables high-throughput, confocal, multi-photon

microscopy setup, developed

fluorescence microscopy imaging, by employing a large number

at LU. The inset shows a 3D

of simultaneously scanned optical foci, together greatly expediting

use of optical microscopy. A set of experiments has been carried

stack of 2D images of an U2OS

(factor 100) the otherwise slow confocal imaging process.

out with these glass devices, providing a direct tool to visualize

(osteosarcoma) cell. (right) Three-

chemo-attractant-induced cell migration through narrow constric-

dimensional trajectory of a gold

Auxiliary tools, methodology and dedicated analysis software have

tions with dimensions up to 1 µm. More narrow constrictions led

nanorod inside a cell, measured

been developed to enable rapid screening of blood samples by AFM

to breakdown of the cell structural integrity.

with this setup.

for micro- and nanoparticles (see below) that serve as markers for the effectiveness of cancer treatment in human patients. This work

The new, combined AFM-light microscopy instrument has been

has been performed in a close collaboration between LU and LPM.

employed in an extensive, collaborative study by the LU and the LUMC (Dr. Jan Lindeman) of the relation between the spatial

Scientific results. One of the prime targets for the NKI-AvL

architecture of the collagen network and the corresponding elastic

team was to investigate mechanisms involved in the spreading

properties of aortic wall tissue. Significant differences were identi-

of breast cancer. A special, glass version of the nanoreactors has

fied between healthy individuals and patients with growing aortic

been developed to visualize key steps in this phenomenon with the

abdominal aneurysms and with aneurysms in Marfan syndrome.

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Dr. Femke Tabak, (Leiden University), NIMIC PhD student on high-speed STM

Distributions, measured by AFM,

Also the effects of various enzymatic treatments were explored.

of the mechanical response (effec-

The same technique has been applied to examine the properties of

tive Young’s modulus) for patients

atherosclerotic plaques.

with Marfan syndrome and aortic abdominal aneurysm (AAA),

The multifocal, two-photon microscope has been used successfully

compared with a healthy control.

to track gold nanorods in their motion through living cells with nano-

The differences in mechanical

meter resolution in three dimensions and over prolonged times, thus

behavior correlate with signifi-

making it possible to directly visualize intracellular dynamics.

cant disturbances in the collagen micro-architecture of the aortic

The rapid AFM screening system has been used to screen blood

wall tissue.

samples for micro- and nanoparticles that serve as markers for the effectiveness of cancer treatment in human patients. The system has been tested successfully on blood serum of actual patients in a collaboration between LPM, LU and the LUMC (Prof. Suzanne Osanto).

2.3 Theme 3: Live nano-imaging of materials processes The target in this part of N I M I C was to develop and apply

time. This special holder type has captured the attention of other

advanced microscopy instrumentation, for High-Resolution

research groups, a patent has been filed, and the TUD spin-off

Transmission Electron Microscopy (TEM) and Scanning Probe

company DENSsolutions is considering the commercialization of

Microscopy (STM and AFM), especially for fundamental studies of

such holders.

atomic-scale, dynamic properties of materials. Another new type of TEM sample holder has been constructed TEM instrumentation. A special TEM sample holder has been

at the TUD that incorporates a MEMS heater, with which metals,

developed at the TUD, with which electrical stimuli can be given to

such as gold or tin, can be deposited in situ. The prime advantage

a metal specimen with a size in the order of a few hundred nano-

of this compact, integrated configuration is that it operates at a

meters. The employed geometry makes it possible to generate

minimum heat load, as a result of which also the thermal drift is

current-induced changes in a thin conducting film – electromigra-

very low.

tion – while visualizing this process with high resolution in real

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Prof. dr. Peter Peters (NKI-Antoni van Leeuwenhoek Hospital and Delft University of Technology), Leader of Project 2.6 on cancer cell migration

3D representations of an AFM image and a TEM image of the same palladium bridge that has undergone massive restructuring under the influence of electromigration.

SPM instrumentation. Two design routes have been explored

the two approaches leads to hybrid structures that combine piezo

at the LU towards high-speed STM imaging (video-rate and faster)

elements for low-speed, large-scale motion and MEMS devices for

of surfaces with atomic resolution. One approach has involved

high-frequency scanning.

clever configurations of ‘traditional’ piezo elements, with which the STM tip is scanned over the surface. In particular, the use

A so-called ‘Sub-surface AFM’ has been developed at the UL, in

of so-called ‘counter-piezo elements’ has been investigated for

which both the sample holder and the tip holder can be subjected

minimization of the scan-motion-induced excitation of vibrations

to ultrasonic excitation at slightly different frequencies in the order

in the microscope. The effect of these piezo structures has been

of several MHz. Spatial maps of the resulting tip motion at the

characterized by direct measurements of the scan-motion-induced

(kHz) difference frequency show sensitivity to buried, sub-surface

vibrations and by observations of the vibration-induced defor-

structures and thereby enables one to ‘look’ below the surface.

mation patterns in atomically resolved, high-speed images. The second approach has been to miniaturize the STM scanner by

Scientific results. At the TUD, an extensive series of in-situ

casting it in the form of a MEMS device. This has the dual advan-

TEM observations has been carried out of electromigration in thin

tage that the natural resonance frequencies of the MEMS device

metal films. Prior to the TEM experiments, the specimens were

itself can be made high, while its mass can be kept so low that

fine-tuned into the desired shape with the use of a Helium Ion

its motion effectively does not couple to the more macroscopic,

Microscope. The in-situ TEM observations have been combined

low-frequency components of the microscope. The combination of

with sensitive electrical measurements (collaboration with Prof.

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Dr. Roman Koning (Leiden University Medical Center), NIMIC Postdoc on correlative TEM-light microscopy for bio-applications

Herre van der Zant, TUD), enabling the direct correlation between the observed geometrical configurations with their electrical conductance. These studies have been carried out for several metals. They have revealed surprising, i.e. counterintuitive current-induced atomic rearrangements that play an essential role in the failure mechanism of these metallic conductors. A MEMS-based heating holder with very low drift was developed at the TUD, with which hot samples of free-standing graphene

Influence of temperature on the sculpting of holes in

irradiation was continued until a small hole was formed.

could be subjected to a focused electron beam in order to sculpt

few-layer graphene by an electron beam (a) at room

The remaining monolayer is almost amorphous at 200°C,

the graphene and form tiny holes and short nanoribbons. The high

temperature (RT), (b) 200°C, (c) 500°C and (d) 700°C. At

polycrystalline at 500°C, and single crystalline at 700°C.

temperature was essential for the self-repair of single C vacancies

RT two holes are formed. The whole area surrounding

Red arrows indicate some of the C ad-atoms trapped at

in the graphene.

the holes has become amorphous. In the experiment

defects. The insets in (b)-(d) show the positions of the

of images (b)-(d), we first removed several graphene

identifiable hexagons (red dots) and the estimated posi-

The high-speed STM project at LU has resulted in atomically

layers, a procedure that is very reproducible at 500°C

tion of the edge (white line). The blue dots in the inset at

resolved, high-speed STM movies on a graphite surface, with a

and 700°C, but hard to control and verify at 200°C. Local

200°C are ad-atoms. Scale bars 1 nm.

maximum frame rate above 100 STM images per second. Even more importantly than this record STM imaging speed, the project has provided a legacy in the form of a set of recommendations

Five consecutive STM images acquired at a record speed of 53 frames/s on a graphite surface.

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Dr.ir. Fredrik Creemer (Delft University of Technology), Leader of Project 3.1 on nanoreactor development

(“dos and don’ts”) for high-speed scanning probe instrumenta-

been performed with a thorough combination of experiments,

tion; these will be put to good use in designs of future STM and

theory and numerical modeling. The most striking conclusion from

AFM setups for various research applications where high imaging

this work is that sub-surface contrast derives from indentation of

speeds are essential.

the tip into the sample, i.e. one effectively probes the local elas-

The LU investigation of sub-surface AFM has concentrated on the

ticity. This is in full contradiction with the widely accepted view in

mechanism by which the tip moves at the difference frequency

this field of research that sub-surface contrast would be caused by

between the ultrasonic waves that are launched through the

variations in the scattering of the ultrasonic wave that propagates

sample and the tip holders and the mechanism by which sub-sur-

through the sample by sub-surface features.

face features generate contrast in this difference signal. This has

NIMIC Final Report | Chapter 2 | Scientific results of NIMIC

Dr. Gerard van Veen (Program Manager at FEI Company), Leader of Projects 4.2 and 4.5 and Leader of Work Package 4 on General Instrumentation for Live Nano-Imaging

Before the N I M I C program started in 2007, the NIMIC consor-

Also a set of deliverables was agreed upon, expressed in terms of

tium defined for itself a series of hard and measurable targets. In

development stages of new instruments and methods, of tests to be

the table below these targets are given together with the levels

delivered and scientific results to be achieved. A complete listing is

realized at the official end date of N I M I C . An elaborate overview

provided in Appendix B, while the results of most of these develop-

of the output generated is given in Appendix A.

ments are also presented in the context of the showcases described

Indicators & deliverables

in Chapter 2. Key indicators are separately discussed below. Target

Realized

Description

Peer reviewed Journal publications

Peer reviewed publications

Peer reviewed Conference publications

The peer reviewed journal publications (Appendix A1) are well

100

198

Citations (according to Web of Science)

on target, with more to come in the years after NIMIC by PhD

Patents filed

students still active or publications under review or in preparation.

Development projects in industry

The peer reviewed conference publications (Appendix A2) illus-

Applications in industry

trate the international activity of NIMIC. Leading conferences have

Other publications (books, media, symposia, etc…)

been visited actively where NIMIC work was presented by invited

Oral conference contributions (outside N I M IC )

talks or by regular oral or poster contributions, often accompanied

Invited talks or lectures

by peer-reviewed publications in the conference proceedings. The

PhD theses finished

sum of both types of publications counts up to 116 and exceeds

Postdoc or support years allocated

the targeted number of 50 publications by more than a factor of 2.

MSc theses finished

The sum of Citations (according to the Web of Science) has already reached 198 (measured in 2012), with some of the high-impact publications (e.g. A1 45, submitted to Science) still to come. So we can conclude that NIMIC will have a much bigger scientific impact than foreseen at the start.

NIMIC Final Report | Chapter 3 | Indicators & deliverables

Ir. Pleun Dona (Senior Mechanical Specialist at FEI Company), development of technology for live TEM imaging

Other output & publications

1. Gas Analyzer of LPM (patent filed)

In total 32 items of additional output are counted, such as book

2. High-Pressure STM of LPM (first commercial version delivered

publications, media appearances and symposium contributions.

in USA)

This is a factor 3 more than originally aimed for. One of the

3. TEM Nanoreactor Holder by FEI (based in a TUD patent license)

reasons for this is that N I M I C broadened the application scope

4. Small-scale production of MEMS Nanoreactors by TUD Dimes

after the Midterm Review by the Strategic Advisory Commission

5. Falcon High-Resolution CMOS camera of FEI

(SAC) in 2010. Consequently N I M I C has been very active in a wide

6. ETEM, now a high-end product sold by FEI

variety of (national) meetings and symposia, such as: Scanning

7. Electromigration TEM holder by Dens Solutions (based on a

Probe Microscopy Day, Physics@FOM, NanoNed and NanoNext

TUD patent)

meetings, FHI meetings, NVvM meetings, etc… (a full overview is given in Appendix A3). At the moment when this report went

New Chairs and positions

to press the number of PhD theses added up to 4 (out of 8). It is

NIMIC is proud that two of its principal investigators have

expected that the targeted number of PhD theses will be reached in

acquired an academic chair during the N IMIC program, in both

the coming years. The planned PhD tracks, along with the Postdoc

cases with a significant component of their recognition deriving

tracks, are given in Appendix A5.

from their role in NIMIC: –– Tjerk Oosterkamp – Professor at Leiden University, Chair of

Participation in national and international networks In parallel with N I M I C and with projects enabled or strongly supported by N I M I C , a large number of collaborative projects has been realized or are still being carried out, both within the Netherlands and in an international context. Prominent examples of these are described in Chapter 4 of this report.

Experimental Physics, Inaugural Speech on 25 May 2012, entitled ‘The blind microscope: from MRI on the nanoscale to academic shaping’ –– Peter Peters – Professor at Delft University of Technology, Chair of High-Resolution Microscopy, Inaugural Speech, pending. –– Bram Koster – Professor University of Leiden, Chair of Ultra structural and molecular imaging. Inaugural speech on 15 may 2009 ‘Cellen in een ander licht zien’

Not only are N I M I C collaborations continued in the academic research area, but also within more industrial contours. A number

Patents

of development projects in industry has incorporated NIMIC

A total of 7 patents have been filed during NIMIC (Appendix A4).

knowledge and will bring it a step further into the phase of

Even though this number is lower than the original target (10), the

commercialization, such as:

number of successful technological developments and inventions

NIMIC Final Report | Chapter 3 | Indicators & deliverables

ele igi M FEI u L on . t at r ntis tdoc Dr.i e i c Pos S r C I o i IM ent (Sen y), N opm pan evel d r Com cto orea nan

in N I MI C has been much larger than 7. This discrepancy reflects

a way that atomic-resolution imaging remains possible under all

the fact that most of these inventions have not been protected by a

conditions. Some of these tools have been developed within the

patent. In most cases, other means of knowledge protection were

context of NIMIC.

considered to be more effective. A typical example is the Falcon C–MOS camera of FEI, which is mainly protected by knowledge

Education

of the fabrication and calibration procedures, which cannot easily

NIMIC research results, working methods and insights have been

be described and protected by a patent and, correspondingly also

incorporated in the curricula and courses of the academic partners,

cannot easily be copied by competitors. The MEMS nanoreactor

for instance in the MSc. courses on Scanning Probe Microscopy

configuration that was initially protected by a patent turned out to

and on Surface Science at Leiden University, or in the Outreach

be a very specific solution for a much larger market.

Program on ‘Nanotechnology’, offered at Leiden University to high-school pupils. Also the technical support staff has absorbed

Start-ups

the knowledge required to design, construct and operate the novel

The most enlightening example of a successful start-up is Leiden

imaging equipment and the supporting tools and instrumentation

Probe Microscopy BV (www.leidenprobemicroscopy.com). This

that has been acquired and developed within NIMIC.

company had been founded just before the start of NIMIC. During the N I MI C program it has grown into a globally acting, special-

Next jobs

ized company. Its current product portfolio comprises special

Appendix A5 gives an overview of the Postdocs and PhD students

scanning-probe microscopes, such as the Reactor-STM, but also

that have worked for NIMIC. Where applicable, their next

a special SXRD reactor chamber for high-pressure surface X-ray

employer is listed. The list shows a well-balanced distribution of

diffraction measurements, an advanced gas analysis system and

next employers, ranging from national to international careers,

various high-level electronic systems and components, including

and from academic to private. Note that all next jobs are clearly

the accompanying control and analysis software.

positioned in the field of high-resolution imaging, at the heart of NIMIC and thereby clearly distributing the new NIMIC knowledge

The TU Delft has co-founded a new company for management

into a wider circle in society.

solutions of in-situ electron microscopy, called DENSsolutions (www.denssolutions.com). The company develops and commercializes tools for the preparation, loading, and stable mounting of samples, for the application of external conditions, and for the characterization of samples inside electron microscopes in such

NIMIC Final Report | Chapter 3 | Indicators & deliverables

Ir. Gerard Verbiest (Leiden University), NIMIC PhD student on sub-surface AFM

National and international visibility of NIMIC The NIMIC program has generated a significant impact also beyond the usual activity horizon of the individual N I M I C projects and extending well beyond the official, six-year duration of this SmartMix program.

Both the research that has been initiated within NIMIC and the

‘NIMIC-style’, live imaging of processes on the nano-scale. NIMIC-

new instrumentation and methodologies that have been devel-

inspired in-situ investigations of materials, biological model systems

oped in our program currently form an essential element in a

and model catalysts are strongly represented throughout the entire

variety of follow-up research programs. One of the highlights here

NanoFront program, including also the other two themes.

is the Dutch national nanotechnology consortium NanoNext (www. nanonext.nl), within which Frenken is the Scientific Director of

Together with three other Dutch scientists, three principal NIMIC

Program 9A, devoted to “Nano-Inspection and Characterization”.

researchers, Peters (NKI-AvL), Koster (LUMC) and Zandbergen (TUD),

NI M I C researchers, in particular Van Veen (FEI), Koster (LUMC),

have initiated the Dutch national high-resolution electron microscopy

Peters (NKI-AvL), Van Baarle (LPM) and Frenken (LU), play a

center NeCEN (Netherlands Center for Electron Nanoscopy; www.

key role in 9 out of the 15 projects in this 12.4 M€ program, in 4

necen.nl). This national facility secured its first rounds of finance in

projects even as the Principal Investigator. N I MIC researchers are

2010 and currently has two dedicated high-resolution Titan Krios

also represented in several of the other 27 NanoNext programs.

TEM systems (FEI) for cryo-imaging of biological specimens. NeCEN is hosted by the Medical Delta (www.medicaldelta.nl), a consor-

In 2012, the Kavli Institute at Delft University of Technology and

tium of Leiden University, Delft University of Technology, Erasmus

the Leiden Institute of Physics (LION) have acquired a prestigious

University and the Leiden University Medical Center and it is located

“Zwaartekracht” (Gravitation) Grant for a joint, 10-year research plan

in Leiden. The NeCEN facility is currently housed in a specially

on “Frontiers of Nanoscience”, in short “Nanofront”. Zandbergen

constructed section of the Cell Observatory at Leiden University

and Frenken were among the six main applicants for this grant. One

and the new building that is presently erected for the whole Science

of the three principal themes of this 51 M€ NanoFront program

Faculty of Leiden University has a special low-vibration, low-inter

is devoted to nanotechnology, and is strongly rooted in ‘NIMIC-

ference, climate-controlled section, fully tailored to the needs of

foundations’. A significant part of this theme is directed towards

three NeCEN TEM setups.

NIMIC Final Report | Chapter 4 | National and international visibility of NIMIC

Dr. Gertjan van Baarle (Director of LPM), development of SPM technology, Leader of extra NIMIC project on gas analysis system development

With the impulse given by N I M I C plus further, large-scale micros-

provides further visibility of NIMIC developments in the large

copy activities that have been added in parallel in Leiden, such

community in the Netherlands of professional users (industries) of

as the new Low-Energy Electron Microscopy facility ESCHER

tools for advanced analysis and microscopy.

(NWO-Groot project), headed by Dr. Sense Jan van der Molen, the MRI-AFM activity of Tjerk Oosterkamp (ERC Starting Grant and

The success of NIMIC has contributed to a collection of awards

NWO Vidi), and the friction force microscopy instrumentation of

and honors bestowed on NIMIC researchers. Some of these

Joost Frenken (FOM Program and ERC Advanced Grant), the total

were modest, such as a poster prize at a conference, some more

body of nanoscale microscopy expertise and instrumentation has

significant, such as the 2011 NEVAC (Netherlands Vacuum Society;

become so big and broad that these activities have been bundled

www.nevac.nl) Prize for Sander Roobol (LU) for his paper about

into the Leiden Center for Ultramicroscopy (lcu.physics.leidenuniv.

high-pressure scanning probe microscopy. NIMIC researchers

nl). This new center is strong in the development and application

were also recipients of several high-impact, high-visibility awards

of high-resolution microscopy techniques and methodology, both

and honors. Frenken (LU) was installed as a member of the Royal

for fundamental research as well as for a growing number of

Netherlands Academy of Arts and Sciences (KNAW; www.knaw.

application-oriented projects on subjects, ranging from solid state

nl) in 2008. In 2010, both Zandbergen (TUD) and Frenken were

physics to life science.

honored with the prestigious Advanced Grant of the European Research Council (ERC; erc.europa.eu). In 2012 Stig Helveg (Haldor

The N I MI C consortium has received a very warm welcome by

Topsøe) received the Berzelius Award from the Nordic Catalysis

COAST (Top Institute for COmprehensive Analytical Science and

Society. In the same year the FOM-Valorization Prize was awarded

Technology; www.ti-coast.com), with an invitation to join this

to Frenken “for combining fundamental research, technology

professional consortium of industrial and academic partners.

development and the generation of new commerce in the market

The mission of COAST is to strengthen analytical science in the

sector” (www.fom.nl). The prize was given to Frenken in January

Netherlands by uniting R&D, human capital and infrastructure.

2013, by Sander Dekker, the Dutch State Secretary for Education,

The N I MI C program was viewed as a relevant complement to

Culture and Science. Finally, in 2013 Fredrik Creemer (TUD)

the spectrum of activities in COAST, adding microscopy down

received the Eurosensors Fellowship Award.

to the atomic scale and live imaging during industrially relevant processes. At present, two N I M I C partners, LU and LPM, have

Very important for future projects along the lines set out in NIMIC

already become members of COAST. The new series of COAST

is that a heritage has been generated of professional, advanced

calls, started in 2013, has significant components that fully reso-

microscopes that will serve the (inter)national research community

nate with the expertise and interests of N I M I C . This channel

for many years to come and that will also form the basis for future

NIMIC Final Report | Chapter 4 | National and international visibility of NIMIC

technological developments, enabling the NIMIC researchers to maintain a leading position. In that respect we specifically mention the high-resolution TEM setup that has been installed by FEI in the Kavli Institute at the TUD, which is fully equipped for in-situ TEM experiments on active model catalysts. This instrument is already used in a variety of new projects that involve NIMIC researchers, for example in the context of the NanoFront project (see above). The high-pressure instrumentation (nanoreactor holder, gas system) that has been set up for similar TEM-experiments at Haldor Topsøe in Denmark will be used in future R&D projects, relevant for the development of new generations of advanced catalysts. A fully equipped scanning probe facility has been developed at LU, with a strong emphasis on high-pressure STM and high-pressure AFM. Next to directly NIMIC-related projects, these microscopes are already being used in further projects, for The FOM Valorisation prize was given to Frenken in January 2013, by Sander Dekker,

example in a collaboration with Shell on Fischer-Tropsch synthesis

the Dutch State Secretary for Education, Culture and Science.

(veni-project of Dr. Violeta Navarro-Paredes) and in a collaboration with Bayer on the Deacon process (veni-project of Dr. Irene Groot). In parallel with the final stages of NIMIC, some of the new instruments that have been developed in NIMIC have been professionalized to the level of a prototype or even to the level of a first-generation product. Prominent examples are several types of NIMIC nanoreactors, productized by DIMES (TUD) and explored for potential productization by FEI (work performed by Lionix). The holders that hold, contact and manipulate the nanoreactors inside TEMs should certainly be mentioned in this context. FEI has developed a successful prototype for live, high-resolution observations under catalytic conditions, while DensSolutions is considering the

N I M I C Final Report | Chapter 4 | National and international visibility of NIMIC

commercialization of a holder dedicated to in-situ electrical stimuli

the development of sample management tools for in-situ elec-

and measurements. LPM has fully entered the productization stage

tron microscopy, such as the special-purpose sample holders for

with the development of a commercial version of the high-pres-

advanced experiments inside a TEM, as explored in the research

sure STM setup that has been constructed within NIMIC at LU.

group of Henny Zandbergen. Similarly, the company Leiden Probe

One complete setup with all peripheral equipment, including full

Microscopy, which had been founded several years before the start

preparation, characterization, handling and storage of samples,

of NIMIC, has experienced a significant growth in its product port-

gas handling and gas compositional analysis, STM scan and data

folio as a result of NIMIC projects and related developments. This

acquisition electronics and software, has been delivered by LPM to

has enabled LPM to mature to a more solid status, grow in size

Brookhaven National Laboratory, while several potential customers

and expand its client base. This has not gone unnoticed and adds

have expressed serious interest in purchasing either the complete

favorably to the visibility of NIMIC. The entrepreneurial spirit that

setup or the essential, high-pressure STM components. For LPM,

has pervaded NIMIC, has certainly had an ‘educational’ influence

this product serves as the nucleus for a dedicated line of new prod-

also outside the direct perimeters of the NIMIC program. One

ucts, including a commercially very successful system for high-pres-

example of a partly NIMIC-inspired, parallel development towards

sure surface x-ray diffraction, again for application to catalytic

the valorization of scientific developments can be found in the start

conditions, and a versatile system to set up a wide range of flows of

of the company Applied Nanolayers BV (ANL) in 2012. ANL focuses

high-purity gas mixtures and to measure gas compositions.

on the large-scale production of high-quality graphene, basic

Further visibility on the valorization side has come from the foun-

elements of which have been investigated by in-situ, high-temper-

dation of the company DENSsolutions 2012, which is focused on

ature STM in Frenken’s group at Leiden University.

NIMIC Final Report | Chapter 4 | National and international visibility of NIMIC

Organization & governance N I M I C Board chair: Van der Zant (TUD) Scientific Director Frenken (UL)

5.1 Governance and operation

Business Director Van der Linde (TUD)

Support TUD and UL

General NIMIC organization N I M I C has been organized with an emphasis on short and direct communication channels. Daily management has been in the hands of a Scientific Director and a Business Director. The formal

WP 1 Nelissen

WP 2 Koster

WP 3 Zandbergen

WP 4 Van Veen

(Albemarle)

(LUMC)

(TUD)

(FEI)

decisive body has been the NIMIC Board, in which all consortium partners were equally represented. The work has been organized in four Work Packages, the first three directly related to the three

NIMIC organization diagram

main thematic areas of NIMIC and the fourth focused on instrumentation development tracks that were related to more than one

The NIMI C Board convened on average five times per year,

single area of application. The end users headed three of the four

monitoring progress and deciding on planning and financial

Work Packages, two from industry and one from a medical institu-

matters. Often, issues such as patent procedures or publication

tion, thus ensuring an optimal focus on user-defined end goals.

approvals required more frequent attention of the Board and these were handled directly without formal meetings. Since the Board consisted of a representation of all partners, subjects were usually swiftly discussed and decided. The NIMIC Management Team consisted of the work package leaders and the two directors. Here, the course set out by the Board was implemented, and, vice versa,

N I M I C Final Report | Chapter 5 | Organisation & Governance

suggestions for implementations were formulated to be presented

5.2 Special taskforces and impulses

to the Board. The combination of involved Work Package leaders and a well-informed and decisive Board proved to be efficient.

During the execution of NIMIC some milestones turned out to be

Each Work Package organized its own meetings and telephone

harder to achieve than initially foreseen. This introduced severe

conferences (up to weekly), in order to discuss progress and

risks of cascading time delays in other parts of the program, in

organize detailed tasks and to coordinate the timing of the individ-

particular for those projects of which the output served as the

ual projects, in particular where there were critical interfaces and

starting point of other projects within the program. The primary

dependencies between these projects.

example of this has been the development of contamination-free combinations of nanoreactors and holders, which was essential for

NIMIC Community

the first high-resolution TEM measurements on active catalysts,

An important instrument for the coherence of the full NIMIC

but which required much more time, effort and care than antici-

community was the combination of two annual NIMIC wide

pated. In these cases, a taskforce was assembled, which reported

meetings. The annual spring meeting was a 1-day event, in which

to the Directors and the Board. The participants of such a taskforce

progress and highlights were presented in talks and posters on

mainly existed of the project and WP leaders that were closely

a project level; most of these presentations were given by the

involved in the specific task at hand. In some cases this required

researchers, i.e. the PhD students and Postdocs. The annual fall

additional involvement of the project team, and in some cases also

meeting was a 2-day event where all work packages presented a

additional manpower and financial resources.

more complete overview of their purpose, progress and planning.

To provide NIMIC with a final, extra boost near completion of the

Of course, also here highlights were celebrated. Both annual meet-

program, the remaining, non-allocated private contributions to

ings formed an important element for N I M I C since the number of

the NIMIC finances were earmarked for additional projects. The

interdependencies in the whole program was large. For instance,

criteria for these funds were focused on the combination of quality

tools developed in one project served to execute tests and experi-

and valorization of NIMIC research. Three projects were selected

ments in others.

in 2011 (in two phases), stimulating three strategic areas: (1) The

The meetings also provided a social component (evenings!), which

further commercialization of the Nanoreactors (project leader

were very helpful in stimulating and fostering communication

FEI), (2) The commercialization of the gas analyzer system (project

between all N I MI C researchers. Many new ideas and initiatives

leader LPM), and (3) the further domain exploration of the Reactor-

saw first daylight during these events. These relationships will

SPM (project leader Leiden University).

outlive N I MI C and form the basis for many future projects and

These extra projects have given extra thrust to NIMIC. Four years

collaborations.

after the start of the program in 2007, most junior researchers of

NIMIC Final Report | Chapter 5 | Organisation & Governance

N I M I C have finished or are in a finalizing phase. The new projects

smooth financial closure phase.

have come at the right time to absorb much of their experience and knowledge and turn these into new momentum.

5.3 Strategic Advisory Committee

5.5 After-NIMIC period For those (PhD) projects that continue beyond 1 July, 2013 (closure date of NIMIC), an After-NIMIC Taskforce has been assembled,

At the start of NI MIC, a Strategic Advisory Committee (SAC) was

based on voluntarily participation. This taskforce will:

called into service, composed of independent external experts

–– supervise the PhD students, where required,

from academic research and from industry (Appendix C). This

–– coordinate the TEM experiments with the nanoreactor holder

committee has convened twice, in Delft and in Leiden. In its first

caretaker (one copy of the nanoreactor holders goes to Haldor

meeting, the SAC was asked to critically review the ambitions and

Topsøe A/S, while one copy remains in the Netherlands, for

project plans of NIMIC. The second SAC meeting served as the midterm review of NIMIC’s progress and valorization strategy.

which a caretaker has been appointed), –– distribute the NI‑MIC nanoreactors between the requesting

Both meetings resulted in recommendations that were gladly

NIMIC partners when the fabrication of the remaining nanore-

incorporated into the NIMIC planning. In October 2013, the SAC

actor batch is completed,

will convene in Leiden for a final review.

5.4 Annual financial checks

–– coordinate new after-NIMIC initiatives and projects. The lifetime for the After-NIMIC Taskforce is currently set to 1 year, i.e. until 1 July, 2014, but this will be extended if desired.

The N I MI C office has requested an annual financial declara-

Regarding the results obtained after 1 July, 2013, i.e. after the offi-

tion from each of its consortium partners, along with an annual

cial closure date of SmartMix funding of NIMIC, the partners will

accountants check. In this way all projects of the partners were

refer to NIMIC in their publications, where these build on NIMIC

jointly subjected to a financial progress and viability check on an

results. The consortium agreement also stipulates that some arti-

annual basis. This has enabled us to maintain financial oversight

cles (e.g. with respect to IP and publications) will survive for some

during the N I MIC period. Also it enabled NIMIC to introduce

years after the NIMIC closure date. This will be mainly applicable

well-balanced financial and organization re-adjustments during the

for those projects that continue ‑‑‑after the official NIMIC closure

execution of the program (see 5.2) and it has greatly facilitated a

date and still generate new outcome.

N I M I C Final Report | Chapter 5 | Organisation & Governance

Appe ndice s

Results NIMIC of theFinal NIMIC Report programme | Appendices | Chapter 2 | Scientific results and value creation

Appendix A, NIMIC Output

NIMIC Final Report | Appendix A | Output

Appendix A1 Peer reviewed Journal publications 1.

B. Song, J. Jansen, F.D. Tichelaar, H.W. Zandbergen,

M.E. Cartas Ventura, L. Crama, D. Stoltz, J.W. Bakker,

mission electron microscopy and first-principles study

V. Navarro-Paredes, I. Taminiau, J.W.M. Frenken, A.

A. Briegel, Chen S., Koster A.J., Plitzko J.M., Schwartz

of Au(100) surface dislocation dynamics’, Surface

Ofitserov, and G.J.C. van Baarle, ‘High-Pressure STM

C.L., Jensen G.J., ‘Correlated light and electron

Science, Feb 2013, V608, pp: 154-164.

for studying catalysis under industrial conditions’,

cryo-microscopy’, Methods Enzymol. 2010; 481:317-41.

Submitted to Rev. Sci. Instr. 7.

B. van den Broek , B.A. Ashcroft , T.H. Oosterkamp, J. van Noort, ‘Parallel Nanometric 3D Tracking

J.M. Thijssen, H. Zandbergen and H.S.J. van der

of Intracellular Gold Nanorods Using Multifocal

‘High-pressure STM study of NO reduction by CO on

Zant, ‘In-situ TEM imaging of grain growth in a Pt

Two-photon Microscopy’, Nanoletters, 13 (3), pp

Pt(100)’, Catalysis Today 154, 51-67, 2010

nanobridge induced by electric current annealing,

980-986, 2013. 13. E.C.M. Disseldorp, F.C. Tabak, A.J. Katan, M.B.S. 8.

B.A. Ashcroft, J. de Sonneville, Y. Yuana, S. Osanto, R.

Hesselberth, T.H. Oosterkamp, J.W.M. Frenken, W.M.

B. Morana, G. Pandraud, J.F. Creemer and P.M. Sarro,

Bertina, M.E. Kuil, T.H. Oosterkamp, ‘Determination of

van Spengen, ‘MEMS-based high speed scanning

‘Characterization of LPCVD amorphous silicon carbide

the size distribution of blood microparticles directly in

probe microscopy’, Rev. Sci. Instrum. 81, 043702, 2010

(a-SiC) as material for electron transparent windows,

plasma using atomic force microscopy and microflu-

Materials Chemistry and Physics’, May 2013, vol. 139,

ids’, Biomedical Microdevices 14), pp. 641-649, 2012.

pp 654-662 B.A. Ashcroft, T.H. Oosterkamp, ‘AutoMicromanager:

W.M. van Spengen, ‘MEMS-based fast scanning probe

B. Morana, R.H. Poelma, G. Fiorentino, J.Wei, J.F.

A microscopy scripting toolkit for LABVIEW and other

microscopes’, Ultramicroscopy 110, 599-604, 2010.

Creemer and P.M. Sarro, ‘Stiction-induced sealing

programming environments’, Rev. Sci. Instrum. 81 (11),

of surface micromachined channels, Journal of

2010, 113708.

Microelectromechanical Systems’, manuscript ready.

15. E.C.M. Disseldorp, F.C. Tabak, A.J. Katan, M.B.S. Hesselberth, T.H. Oosterkamp, J.W.M. Frenken, W.M.

10. B.L.M. Hendriksen, M.D. Ackermann, R. van Rijn, D. 5.

14. F.C. Tabak, E.C.M. Disseldorp, G.H. Wortel, A.J. Katan, M.B.S. Hesselberth, T.H. Oosterkamp, J.W.M. Frenken,

9. 4.

12. C.T. Herbschleb, S.C. Bobaru and J.W.M. Frenken,

B. Gao, M. Rudneva, K.S. McGarrity, Q. Xu, F. Prins,

Nanotechnology.’ 22, p 25705-205711, 2010. 3.

11. C.T. Herbschleb, P.C. van der Tuijn, Q. Liu, G. Verdoes,

G. Gajewski, C.W. Pao, D.J. Srolovitz, ‘In situ trans-

van Spengen, Reply to ‘comment on MEMS-based

B. Song, G. Schneider, Q. Xu, G. Pandraud, C. Dekker

Stoltz, I. Popa, O. Balmes, A. Resta, D. Wermeille, R.

high speed scanning probe microscopy’ Rev. Sci. Instr.

and H.W.J. Zandbergen, ‘Atomic-scale electron-beam

Felici, S. Ferrer and J.W.M. Frenken, ‘The role of steps

81 (2010) 117102.

sculpting of defect-free graphene nanostructure’,

in surface catalysis and reaction oscillations’, Nature

Nanoletters, 11 (6), pp: 2247-2250, 2011.

Chemistry 2, 730-734, 2010

NIMIC Final Report | Appendix A | Output

16. G. Dong, E.B. Fourré, F.C. Tabak, J.W.M. Frenken, ‘How

22. J. Gustafson, R. Westerström, O. Balmes, A. Resta, R.

26. J.F. Creemer, S. Helveg, G. Hovling, S. Ullmann, A.M.

boron nitride forms a regular nanomesh on Rh(111)’,

van Rijn, X. Torrelles, C.T. Herbschleb, J.W.M. Frenken,

Molenbroek, P. M Sarro, H. Zandbergen, ‘Atomic-

Phys. Rev. Letters 104 (2010) 096102.

E. Lundgren, ‘Catalytic activity of the Rh surface oxide:

scale Electron Microscopy at Ambient Pressure’, Ultra

CO oxidation over rh(111) under realistic conditions’, J.

microscopy 108 (2008), pp. 993-998. Press Review:

Phys. Chem. 114 (2010) pp: 4580-4583.

Chemical 8t Engineering News, Latest News, July 24,

17. G.J. Verbiest, J.N. Simon, T.H. Oosterkamp, M.J. Rost, ‘Sub surface atomotic force mircroscopy: towards a quatitative understanding’, Nanotechnology, V23(14)

2008 23. J. Gustafson, R. Westerström, O. Balmes, A. Resta, R. van Rijn, X. Torrelles, C.T. Herbschleb, J.W.M. Frenken,

27. J.F. Creemer, S. Helveg, P. Kooyman, A.M. Molenbroek,

E. Lundgren, Reply to “Comment on ‘Catalytic activity

H.W. Zandbergen, P.M. Sarro, ‘A MEMS Reactor for

of the Rh surface oxide: CO oxidation over Rh(111)

Atomic-scale Microscopy of Nanomaterials under

‘Sensitivity in SubSurface-AFM: Detection of the

under realistic conditions’, J. Phys. Chem. C 114 (2010)

Industrially Relevant Conditions’, J. Microelectromech.

Subsurface Signal’, Phys. Rev. Lett. (submitted)

22373-22373.

Syst. 19, 1-11, 2010.

2012, pp 14504. 18. G.J. Verbiest, T.H. Oosterkamp, and M.J. Rost,

19. G.J. Verbiest, T.H. Oosterkamp, and M.J. Rost,

24. J. Pierson, J. Vos, J.R. McIntosh, P.J. Peters,

28. J.H.N. Lindeman, B.A. Ashcroft, J.W.M. Beenakker.

‘Sensitivity in SubSurface-AFM: Tip-Sample Interaction

‘Perspectives on electron cryo-tomography of vitreous

M.H. van Es, N.B.R. Koekkoek, F.A. Prins, J.F.

in Heterodyne Force Microscopy’, Ultramicroscopy

cryo-sections’, Journal of Electron Microscopy, 60,

Tielemans, H. Abdul-Hussien, R.A. Bank, T.H.

(submitted)

S93-S100, 2011.

Oosterkamp, ‘Distinct defects in collagen micro-architecture cause vessel wall failure in the aortic abdomi-

20. H. Wolinski, Kolb D., Hermann S., Koning R.I., Kohlwein

25. J. Pierson, U. Ziese, M. Sani, P.J. Peters

Exploring

S.D., ‘A role for seipin in lipid droplet dynamics and

vitreous cryo-section-induced compression at the

inheritance in yeast’. J. Cell. Sci. 2011 Nov 15; 124(Pt

macromolecular level using electron cryo-tomography;

22), p.p. 3894-904.

80S yeast ribosomes appear unaffected. Journal of Structural Biology, 21(2), 345-34, 2011.

21. J.W.M. Beenakker, B.A. Ashcroft, J.H.N. Lindeman

nal aneurysm and Marfan syndrome’, PNAS 107 (2010) pp: 862-865 29. J.W.M. Beenakker, J.H.N. Lindeman, B.A. Ashcroft, M.H. van Es, N.B.R. Koekkoek, F.A. Prins, H. AbdulHussien, R.A. Bank, T.H. Oosterkamp, ‘Distinct defects

and T.H. Oosterkamp, ‘Mechanical Properties of the

in collagen micro-architecture underlie vessel wall

Extracellular Matrix of the Aorta Studied by Enzymatic

failure in growing aortic abdominal aneurysms and

Treatments’, Biophysical Journal, Volume 102 April

aneurysms in Marfan syndrome’, Atherosclerosis 11

2012, 1731–1737

(2010) 101

NIMIC Final Report | Appendix A | Output

30. J.W.M. Frenken and B.L.M. Hendriksen, ‘The reactor

35. M. Rudneva, B. Gao, F. Prins, Q. Xu, H. Zandbergen and

40. R. van Rijn, M.D. Ackermann, O. Balmes, T. Dufrane,

STM: a real-space probe for operando nanocatalysis’,

H.S.J. van der Zant, ‘In-situ TEM imaging of electromi-

A.C. Geluk, H. Gonzales, H. Isern, E. de Kuyper, L. Petit,

MRS Bulletin 32, 1015-1021, 2007.

gration in Pt nanowires’, accepted for Microscopy &

V.A. Sole, D. Wermeille, R. Felici, J.W.M. Frenken,

Microanalysis in 2012.

‘Ultrahigh vacuum/high-pressure flow reactor for

31. J.W.M. Frenken and T.H. Oosterkamp, ‘When mica and water meet’, Nature 463 (2010) pp: 38-39. 32. L.F. van Driel, Valentijn J.A., Valentijn K.M., Koning R.I., Koster A.J., ‘Tools for correlative cryo-fluorescence

surface x-ray diffraction and grazing incidence small 36. M. Rudneva, E. van Veldhoven, S. Malladi, D. Maas, H.W. Zandbergen, ‘Novel Nanosample preparation

for industrial catalysis’, Rev. Sci. Instrum. 81 (2010)

with a helium ion Microscope’, Journal of Material

014101.

Research, 28 (2013), pp 1013;1020. 41. R. van Rijn, O. Balmes, A. Resta, D. Wermeille, R.

microscopy and cryo-electron tomography applied to whole mitochondria in human endothelial cells’. Eur. J. Cell. Biol. 2009 Nov, 88(11), p.p.669-684. 33. L. Mele, F. Santagata, E. Iervolino, M. Mihailovic, T. Rossi, A.T. Tran, H. Schellevis, J.F. Creemer, P.M. Sarro,

37. M. Rudneva, T. Kozlova, H.W. Zandbergen, ‘The use

Westerström, J. Gustafson, R. Felici, E. Lundgren,

of STEM imaging to analyze thickness variations due

J.W.M. Frenken, ‘Surface structure and reactivity of

to electromigration-induced mass transport in thin

Pd(100) during CO oxidation near ambient pressures’,

polycrystalline nanobridges’, Ultramicroscopy (2013),

PCCP 13 (2011) 13167-13171.

in press 42. R. van Rijn, O. Balmes, R. Felici, J. Gustafson, D.

‘A molybdenum MEMS microhotplate for high-temperature operation’, Sensors and Actuators A: Physical,

angle x-ray scattering studies close to conditions

38. M. Vulovic, Rieger B., van Vliet L.J., Koster A.J.,

Wermeille, R. Westerström, E. Lundgren, J.W.M.

Vol. 188, dec. 2012, pp. 173-180. Elsevier. Available

Ravelli R.B., ‘A toolkit for the characterization of CCD

Frenken, Comment on “CO oxidation on Pt-group

online.

cameras for transmission electron microscopy’. Acta

metals from ultrahigh vacuum to near atmospheric

Crystallogr. D. Biol. 2010 Jan; 66(Pt 1), p.p. 97-109.

pressures. 2. Palladium and Platinum”, J. Phys. Chem.

34. L. Mele, F. Santagata, G. Pandraud, B. Morana, F. Tichelaar, J.F. Creemer and P.M. Sarro, ‘Wafer

C 114 (2010) 6875-6876. 39. M.E. Messing, R. Westerström, B.O. Meuller, S.

Level Manufacturing of MEMS Nanoreactors

Blomberg, J. Gustafson, J.N. Andersen, E. Lundgren, R.

43. R.I. Koning and A.J. Koster, ‘Cryo Electron Tomography

for in situ Microscopy’, J. Micromechanics and

van Rijn, O. balmes, H. Bluhm, K. Deppert, ‘Generation

in Biology and Medicine’, Anal of Anatomy, 191, pp.

Microengineering, V.20 (2010), 085040.

of Pd model catalyst nanoparticles by spark discharge’,

427-445, 2009.

J. Phys. Chem. C 114 (2010) p.p. 9257-9263.

NIMIC Final Report | Appendix A | Output

44. R.I. Koning, Kutchoukov V.G., Hagen, C.W and

49. T. Yokosawa, T. Alan, G. Pandraud, B. Dam, H.W.

Koster, A.J. ‘Nanofabrication of a gold fiducial array

Zandbergen, ‘In-situ TEM on (de)hydrogenation of

on specimen support for electron tomography’,

Pd at 0.5–4.5 bar hydrogen pressure and 20–400°C’.

Ultramicroscopy (2013), Accepted.

Ultramicroscopy, 12(1), 47-52, 2012.

45. S.B. Vendelbo, C.F. Elkjær, H. Falsig, I. Puspitasari, P.

50. T.H. Oosterkamp, M. Poggio, C.L. Degen, H.J. Mamin,

Dona, L. Mele, B. Morana, B.J. Nelissen, R. van Rijn,

D. Rugar, ‘Frequency domain multiplexing of force

J. F. Creemer, P. J. Kooyman, S. Helveg , ‘Supporting

signals with application to magnetic resonance force

Online Material for Oscillatory Oxidation of Carbon

microscopy’, Appl. Phys. Letters. 96 (2010), 083107.

Monoxide by Platinum Nanocrystals’, to be submitted 51. U. Hejral, R. van Rijn, S.B. Roobol, W.G. Onderwaater,

to Science.

O. Balmes, H. Isern, R. Felici, J.W.M. Frenken, A. 46. S.B. Vendelbo, P.J. Kooyman, J.F. Creemer, B. Morana,

Stierle,‘Oxidation and reduction of Pd(100) and aero-

L. Mele, C.C. Appel, B.J. Nelissen, and S. Helveg,

sol-deposited Pd nanoparticles’. Phys. Rev. B, V83

‘Method for local temperature measurement in a nano-

(2011) 115440.

reactor for in situ high-resolution electron microscopy’, Ultramicroscopy 27 April 2013, In Press.

52. Y. Yuana, T.H. Oosterkamp. S. Bahatyrova, B.A. Ashcroft, P.G. Rodriguez, R.M. Bertina. S. Osanto,

47. S. Roobol, ‘ReactorSTM en ReactorAFM’, NEVAC Megazine, V1, 2012.

‘Atomic force microscopy: a novel approach to the detection of nanosized blood microparticles’, J. of Thrombosis and Haemostasis, V.8 (2010), pp. 315-323.

48. T. Alan, T. Yokosawa, J. Gaspar, G. Pandraud, O. Paul, J.F. Creemer, P.M. Sarro, H.W. Zandbergen, ‘Microfabricated channel with ultra-thin yet ultra-strong windows enables electron microscopy under 4-bar pressure’. Applied Physics Letters, 100(8), 081903, 2012.

NIMIC Final Report | Appendix A | Output

Appendix A2 Peer reviewed Conference publications 1.

B. Morana, G. Fiorentino, G. Pandraud, J.F. Creemer coating against oxidation of LPCVD SiC microhot-

Surface Science (3S’10)’, St. Christoph am Arlberg,

plates’, 2013 IEEE 26th International Conference on

Austria, March 7-14, 2010.

Micro Electro Mechanical Systems (MEMS), Jan. 20-24,

H.T.M. Pham, G. Pandraud, F.D. Tichelaar, and P.M.

2013, Taipei, Taiwan. IEEE, Piscataway, NJ, USA, 2013,

Sarro ‘LPCVD amorphous SiCx for freestanding elec-

pp. 484-487.

tron transparent windows”, 23rd IEEE International

C.T. Herbschleb, P.C. van der Tuijn, A. Ofitserov, G.J.C van Baarle, G. Verdoes, E. Cañas-Ventura, L. Crama, J.W. Bakker, V. Navarro-Paredes, I. Taminiau, J.W.M.

B. Song, F.D. Tichelaar, H.W. Zandbergen, ‘Real-time

Frenken, ‘Live catalysts under industrial conditions

MEMS’ 10, 24-28 Jan. 2010, Hong Kong, China. IEEE,

atomic resolution study of Gold (100) surface dynam-

imaged atomic resolution’, European Conference

Piscataway, NJ, USA, pp. 572-575.

ics at room temperature and 77 K’, 17th International

on Surface Science (ECOSS-27), Groningen, The

Microscopy Congress, Rio de Janeiro, Brazil, 19-24

Netherlands, 2010.

B. Morana, F. Santagata, L. Mele, M. Mihailovic, G.

September 2010, 2 page abstract number’ M19512

Pandraud, J.F. Creemer, P.M. Sarro, ‘A silicon carbide

included.

mems microhotplate for nanomaterial characterization in tem’. Proceedings MEMS 2011, p572-575, Cancun,

10. C.T. Herbschleb, P.C. van der Tuijn, Q. Liu, A. Ofitserov, G.J.C. van Baarle, G. Verdoes, M.E. Cañas-Ventura, L.

B. Song, G. Schneider, G. Pandraud and H. W.

Crama, J.W. Bakker, V. Navarro-Paredes, I. Taminiau,

Zandbergen, ‘HREM imaging of Au nanoparticles on

J.W.M. Fenken, ‘Live catalysts under industrical condi-

graphene at 200-600 C’, 17th International Microscopy

tions imaged with atomic resolution’, Gordon Research

B. Morana, G. Pandraud, F. Santagata, J.F. Creemer,

Congress, Rio de Janeiro, Brazil, 19-24 September

Conference “Catalysis”, New London, U.S.A., 27 June

P.M. Sarro, ‘Stiction-driven sealing of surface microma-

2010,2 page abstract & poster.

- 2 July 2010.

Mexico, 23-27 Jan. 2011. 3.

C.T. Herbschleb, ‘Live catalysts under industrial conditions imaged with atomic resolution: Symposium on

B. Morana, J.F. Creemer, F. Santagata, C.-C. Fan,

Conference on Micro Electro Mechanical Systems -

and P.M. Sarro, ‘ALD aluminium oxide as protective

chined channels,’ 2012 IEEE 25th International Conference on Micro Electro Mechanical Systems

B. Song, G.F. Schneider., Q. Xu, G.Pandraud, C. Dekker,

11. C.T. Herbschleb, S.C. Bobaru, J.W.M. Frenken, ‘Does

(MEMS), Jan. 29-2012-Feb. 2 2012, Paris, France. IEEE,

H. Zandbergen, ‘Atomic-Scale Electron-Beam Sculpting

surface structure influence NO reduction, Symposium

Piscataway, NJ, USA, 2012, pp. 329-332.

of Defect-Free Graphene Nanostructures’. Microsc.

on Surface Science (3S’09)’, St. Moritz, Switzerland,

Microanal. 17 (2011) pp: 526-527. August 7-11 (2011)

March 8 -14, 2009.

Nashville Tennessee, 2 page abstract & poster.

NIMIC Final Report | Appendix A | Output

12. D. Stoltz, C.T. Herbschleb, P.C. van der Tuijn, G.J.C.

16. F.C. Tabak, G.H. Wortel, P.C. van der Tuijn, J.W. Bakker,

21. G.J. Verbiest, J.N. Simon, T.H. Oosterkamp, M.J. Rost,

van Baarle, I.A.J. Taminiau, M.E. Cañas Ventura, E. de

J.W.M. Frenken, W.M. van Spengen, ‘The develop-

‘SubSurface AFM: Towards a quantitative under-

Kuyper, A.C. Geluk, W.J. v.d. Geest, J.W.M. Frenken,

ment of an easy-to-use, versatile MEMS SPM scanner,

standing of SubSurface AFM’, ECOSS’28 conference,

‘Reactor SPM: European Conference on Surface

3S’10’, St. Christoph am Arlberg, Austria, 7-13 March

European Conference on Surface Science, Wroclaw,

Science (ECOSS-25)’, Liverpool, UK, 27 July - 1 August

2010.

Poland, 29 August 2 September 2011.

2008. 17. F.C. Tabak, ‘Integration of a MEMS z-scanner in 13. D.G. Georgieva, J. Jansen, I. Sikharulidze, H.W. Zandbergen, J.P. Abraham, ‘Evaluation of Medipix

AFM:Tip-sample interaction in SubSurface-AFM’, 4th

Edinburgh, UK, 3-7 September 2012.

Multifrequency Conference, Conference on using

2 Detetor for Recordig Electron Diffraction Data in Low Dose Conditions’, 17th International Microscopy

SPM with multiple frequencies, Madrid, Spain, 15-17 18. F.C. Tabak, H. Borsboom, P.C. van der Tuijn, J.W.M.,

Congress, Rio de Janeiro, Brazil, 19-24 September

Frenken, W.M. Spengen, ‘MEMs z-scanners as fast

2010.

add-on in scanning tunneling microscopy’, ISPM 2012, Canada, Toronto 15-18 June.

14. D. Maas, E.W. van der Drift, E. van Veldhoven, J. Meessen, M. Rudneva and P. Alkemade, ‘Nano-

22. G.J. Verbiest, T.H. Oosterkamp, M.J. Rost, ‘SubSurface

a Scanning Tunneling Microscope’, ECOSS29,

October 2012. 23. G.J. Verbiest, T.H. Oosterkamp, M.J. Rost, ‘SubSurface AFM:Tip-sample interaction in SubSurface-AFM’, MRS Fall meeting, Boston, Boston, USA, 25-30 November

19. G. Pandraud, R.I. Koning and H. Zandbergen, ‘A

engineering with a focused helium ion beam’, MRS

MEMS Nanoreactor for Biological Sample Studies in

Proceedings 2011, pp 1354-1369.

Transmission Electron Microscopy’, IEEE Sensors 2009, Christchurch, New Zealand, 2009.

15. F. Santagata, L. Mele, M. Mihailovic, B. Morana, J.F.

2012. 24. I. Puspitasari and P.J. Kooyman, ‘Noble metal catalyst reduction in hydrogen, a quasi in-situ TEM study’, NCCC, Noordwijkerhout, The Netherlands, March 2010.

Creemer and P.M. Sarro, ‘Wafer level encapsulation

20. G.J. Verbiest, J.N. Simon, T.H. Oosterkamp, M.J. Rost,

techniques for a MEMS microreactor with integrated

‘SubSurface AFM: Towards a quantitative under-

heat exchanger’, Proc. IEEE Sensors 2009, 25-28 Oct.

standing of SubSurface AFM’, 3rd Multifrequency

S. Vendelbo, J.F. Creemer, P.J. Kooyman, ‘Noble

2009, Christchurch, New Zealand. IEEE, Piscataway, NJ,

Conference, Conference on using SPM with multiple

metal catalyst reduction in hydrogen, a quasi and

USA, pp. 799-802.

frequencies, Madrid, Spain 13-15 March 2011.

in-situ TEM study’, The 2nd International Symposium

25. I. Puspitasari, B. Morana, L. Mele, F. Santagata,

on Advanced Electron Microscopy for Catalysis and Energy Storage Materials. February 5th to 8th 2012. Berlin – Germany.

NIMIC Final Report | Appendix A | Output

26. I. Puspitasari, P. Saputra, B. Morana, L. Mele, F.

30. J.W.M. Beenakker, J.H.N. Lindeman, B.A. Ashcroft,

34. L. Mele, B. Morana, C. de Boer, J.F. Creemer and P.M.

Santagata, J.F. Creemer, F. Kapteijn, P.J Kooyman ,

M.H. van Es, N.B.R. Koekkoek, F.A. Prins, H. Abdul-

Sarro, ‘Low-temperature wafer-level packaging of a

‘Particle imaging and flow visualization in in-situ TEM

Hussien, R.A. Bank, T.H. Oosterkamp, ‘Distinct defects

MEMS microreactor with a lateral feedthrough by local

nanoreactors’, Microscopy and Micro Analysis 2012,

in collagen micro-architecture underlie vessel wall

PECVD TEOS deposition’, Proc. EUROSENSORS XXIIl,

Phoenix, Arizona, USA, July 29-August 2, 2012.

failure in growing aortic abdominal aneurysms and

Lausanne, Switzerland, 6- 9 Sept. 2009.

aneurysms in Marfan syndrome’, 78th EAS Congress, 27. J. Jansen, H.W. Zandbergen, ‘Computer assisted drift

Hamburg, Germany, 20-23 June 2010.

correction for transmission electron microscopes’, 17th International Microscopy Congress, Rio de Janeiro, Brazil, 19-24 September 2010. 28. J.F. Creemer, F. Santagata, B. Morana, L. Mele, T. Alan,

35. M. Rudneva, B. Gao, H.S.J van der Zant, H.W. Zandbergen, ‘In-situ electrical characterization

31. J.W.M. Beenakker, J.H.N. Lindeman, B.A. Ashcroft,

combined with simultaneous TEM observation’, 17th

M.H. van Es, N.B.R. Koekkoek, F.A. Prins, H. Abdul-

International Microscopy Congress, Rio de Janeiro,

Hussien, R.A. Bank, T.H. Oosterkamp, ‘Distinct defects

Brazil, 19-24 September 2010, 2 page abstract, poster.

in collagen micro-architecture underlie vessel wall 36. M.A. van Huis, G. Pandraud, J.F. Creemer, H.W.

E. Iervolino, G. Pandraud, and P.M. Sarro, ‘An all-in-one

failure in growing aortic abdominal aneurysms and

nanoreactor for high-resolution microscopy on nano-

aneurysms in Marfan syndrome’, Cardio Vasculaire

Zandbergen, ‘Atomic Resolution Imaging of nanoparti-

materials at high pressures’, 24th IEEE International

Conferentie 2011, Noordwijkerhout, 17-18 March 2011.

cles during In-Situ Heating at Temperatures up to 1000

Conference on Micro Electro Mechanical Systems - MEMS ‘11, 23-27 Jan. 2011, Cancun, Mexico. IEEE, Piscataway, NJ, USA, 2011, pp. 1103-1106.

K’, 17th International Microscopy Congress, Rio de 32. J.W.M. Beenakker, B.A. Ashcroft, J.H. Lindeman, T.H. arterial wall’. ISPM 2012, 15-18 June, Toronto, Canada,

29. J.N. Simon, G.J. Verbiest, T.H. Oosterkamp, M.J. Rost, ‘Subsurface AFM: towards nondestructive 3D micros-

Janeiro, Brazil, 19-24 September 2010.

Oosterkamp, ‘Unravelling the collagen network of the 37. M.A. van Huis, N.P. Young, G. Pandraud, A.I. Kirkland, H.W. Zandbergen, ‘Surface roughening and partial 33. L. Mele, Santagata F., Iervolino E., Mihailovic M., Rossi

melting of Au aoparticles Observed with In-situ High

copy’, ECOSS27, Groningen, 29 August - 3 September

T., Tran A.T., Schellevis, H., Creemer J.F., Sarro P.M.,

Resolution Transmission Electron Microscopy’, 17th

2010.

‘Sputtered molybdenum as conductive material for

International Microscopy Congress, Rio de Janeiro,

high-temperature microhotplates’, In Technical Digest

Brazil, 19-24 September 2010.

of the 16th International Solid-State Sensors, Actuators and Microsystems Conference (TRANSDUCERS 2011) (pp. 2690-2693). Beijing, China: IEEE.

NIMIC Final Report | Appendix A | Output

38. M.E. Cañas-Ventura, A. Ofitserov, W.G. Onderwaater,

42. P.J. Peters, ‘Nanopod Mediated Cell Migration’, confer-

47. Q. Liu, J.W. Bakker, V. Navarro-Paredes, C.T.

C.T. Herbschleb, Q. Liu, V. Navarro, J.W. Bakker, D.

ence Instituto de Biopysica UFRJ, Spain, 17-24 sept.

Herbschleb, A. Ofitserov, G.J.C. van Baarle and J.W.M.

Stoltz, I. Taminiau, P.C van der Tuijn, G. Verdoes, A.C.

2010

Frenken, ‘Study of NO reduction by hydrogen on

Geluk, E. de Kuyper, G.J.C van Baarle, R.C.T. Koehler, C.F. Overgauw, J.W.M. Frenken, ‘ReactorAFM, imaging

a Pt(100) model catalyst in a high-pressure STM’, 43. P. Puspitasari, P.J. Kooyman, ‘Heterogeneous Catalyst

supported catalysts at work’, DPG Frühjahrstagung

Preparation: towards real in situ TEM studies’, 17th

2010, Regensburg, Germany, 21-26 March 2010.

International Microscopy Congress, Rio de Janeiro, Brazil, 19-24 september 2010, 2 page abstract, poster.

39. M.I. Rudneva, E. van Veldhoven, M.S. Shu, D. Maas, H.W. Zandbergen, ‘Preparation of electron transpar-

ECOSS-27, Netherlands, Groningen, 29 August - 3 September 2010. 48. R. van Rijn, ‘A structural view of Pd(100) as a model catalyst’, Gordon Research Conferences “Catalysis”,

44. P.J. Kooyman, F. Devred, H.W. Zandbergen, ‘Avoiding

New London, U.S.A., 27 June - 2 July 2010.

ent samples of pre-selected areas using a Helium Ion

additional carbon from embedding resin for HRTEM

Microscope’, 17th International Microscopy Congress,

sample preparation using cryo-ultramicrotomy’, 17th

Rio de Janeiro, Brazil, 19-24 September 2010.

International Microscopy Congress, Rio de Janeiro,

D. Stoltz, Q. Liu, V. Navarro-Paredes, J.W. Bakker, I.

Brazil, 19-24 September 2010.

Taminiau, W.G. Onderwaater, P.C. van der Tuijn, M.

40. M. Rudneva, B. Gao and H. Zandbergen, ‘In-Situ Measurements of the Electrical Properties of

49. S.B. Roobol, M.E. Cañas-Ventura, C.T. Herbschleb,

Bergman, R.C.T. Koehler, A. Ofitserov, G.J.C. van 45. P.V. Afanasyev, A.L. van Bueren, C. Tomova, P. Dona,

Baarle, J.W.M. Frenken, ‘The ReactorAFM: in-situ

Nanosamples at Different Temperatures combined with

L.C.J.M. Oomen, E.A.M. Veraar, C. Lopez-Iglesias

observations of model catalysts under realistic

Simultaneous TEM Observation’, 5th Meeting of the

and P.J. Peters, ‘Migration of mammalian cells in a

conditions using Atomic Force Microscopy’, Gordon

International Union of Microbeam Analysis Societies

novel nanochamber; its potential use for cryo-elec-

Research Conference “Chemical reactions at surface”,

2011 (IUMAS-V), 22-27 May 2011, Seoul, South Korea.

tron tomography’, EMC 2012, Manchester, UK, 16-21

Ventura, U.S.A., 6-11 February 2011.

September 2012. 41. M. Rudneva, E. van Veldhoven, D. Maas and H. Zandbergen, ‘Helium Ion Microscope as a Sculpting

50. S.B. Roobol, M.E. Cañas-Ventura, C.T. Herbschleb, Q. 46. Q. Liu, C.T. Herbschleb, J.W. Bakker, V. Navarro-

Liu, V. Navarro-Paredes, J.W. Bakker, I. Taminiau, W.G.

Tool for Nanosamples’, 5th Meeting of the International

Paredes, M.E. Cañas-Ventura, P.C. van der Tuijn, A.

Onderwaater, P.C. van der Tuijn, R.C.T. Koehler, A.

Union of Microbeam Analysis Societies 2011

Ofitserov, G.J.C. van Baarle, J.W.M. Frenken, ‘Study of

Ofitserov, G.J.C. van Baarle, J.W.M. Frenken, ‘In-situ

(IUMAS-V), 22-27 May, 2011, Seoul, South Korea.

NO reduction by H2 on a Pt(110) model catalysts in a

AFM for catalysis research at high pressures and

high-pressure STM’, Symposium on Surface Science

temperatures’, NC-AFM 2011, Lindau, Germany, 18-22

2011, Baqueira Beret, Spain, 6-12 March 2011.

September 2011.

NIMIC Final Report | Appendix A | Output

51. S.B. Roobol, M.E. Cañas-Ventura, C.T. Herbschleb, Q.

55. S.B. Vendelbo, S. Helveg, J.F. Creemer, B. Morana, L.

59. U. Hejral, R. van Rijn, S.B. Roobol, W.G. Onderwaater,

Liu, V. Navarro-Paredes, J.W. Bakker, I. Taminiau, W.G.

Mele, C.C. Appel, B.J. Nelissen, and P.J. Kooyman, ‘In

O. Balmes, H. Isern, R. Felici, J.W.M. Frenken, A.

Onderwaater, P.C. van der Tuijn, R.C.T. Koehler, A.

situ HRTEM of a working catalyst using a nanoreactor

Stierle, ‘Size and shape changes of Pt nanoparticles

Ofitserov, G.J.C. van Baarle, J.W.M. Frenken, ‘Bridging

at 1 bar’, 14th NCCC, Noordwijkerhout, March 11-13,

on a-Al2O3(0001) during CO oxdiation reactions’,

the pressure and materials gap with the reactor AFM’.

2013

ECOSS28, Wroclaw, Poland, 28 August - 2 September

ECOSS29, Edinburgh 3-7 September 2012.

2011. 56. S.B. Vendelbo, C.F. Elkjær, I. Puspitasari, J.F. Creemer,

52. S.B. Vendelbo, J.F. Creemer, S. Helveg, B. Morana, L.

P. Dona, L. Mele, B. Morana, B.J. Nelissen, S. Roobol,

60. V. Navarro-Paredes, S.B. Roobol, R. van Rijn, Q. Liu,

Mele, A.M. Molenbroek, P.M. Sarro, H.W. Zandbergen

R. van Rijn, S. Helveg, P. J. Kooyman, ‘Atomic-Scale

C.T. Herbschleb, J.W. Bakker, M.E. Cañas-Ventura,

and P.J. Kooyman, ‘In situ HRTEM of a catalyst using

Imaging of Pt and Pd Nanoparticle Catalysts During

O. Balmes, D. Wermeille, A. Resta, R. Felici, J.W.M.

a nanoreactor at 1 bar’, NCCC-XII - Netherlands’

CO Oxidation at 1 Bar Reaction Conditions’, E-MRS

Frenken, ‘Fischer-Tropsch synthesis followed at high

Catalysis and chemistry Conferece, Noordwijkerhout,

Strasbourg May 27-31, 2013

pressures with STM and SXRD’, ECOSS27, Groningen,

28 febr.- 2 maart 2011.

29 August - 3 September 2010. 57. S.B. Vendelbo, C.F. Elkjær, I. Puspitasari, J.F. Creemer,

53. S.B. Vendelbo, P.J. Kooyman, ‘Local temperature

P. Dona, L. Mele, B. Morana, B.J. Nelissen, S. Roobol,

61. V. Navarro-Paredes, S.B. Roobol, R. van Rijn, Q. Liu,

measurement of 1 bar gas in a TEM nanoreactor’,

R. van Rijn, S. Helveg, P.J. Kooyman, ‘Atomic-Scale

O. Balmes, D. Wermeille, A. Resta, R. Felici, J.W.M.

Microscopy and Micro Analysis 2012, Phoenix, Arizona,

Imaging of Pt and Pd Nanoparticle Catalysts During CO

Frenken, ‘Fischer-Tropsch synthesis followed at high

USA, July 29-August 2, 2012.

Oxidation at 1 Bar Reaction Conditions’, Microscopy

pressures with STM and XRD’, Symposium on Surface

and Micro Analysis 2013, Indianapolis, Aug 4-8, 2013.

Science 2010, St. Anton am Arlberg, Austria, 7-13

54. S.B. Vendelbo, J.F. Creemer, S. Helveg, B. Morana, L. Mele, C.C. Appel, P.M. Sarro, B.J.

March 2010. 58. S.B. Vendelbo, C.F. Elkjær, J.F. Creemer, P. Dona, L. 62. V. Navarro-Paredes, S.B. Roobol, R. van Rijn, Q. Liu,

Nelissen, H.W. Zandbergen and P.J. Kooyman, ‘Local

Mele, B. Morana, B.J. Nelissen, P.J. Kooyman, S.

temperature measurement of 1 bar gas in a TEM

Helveg , ‘Atomic-scale imaging of catalysts at 1 bar

O. Balmes, D. Wermeille, A. Resta, R. Felici, J.W.M.

nanoreactor’, The 2nd International Symposium

reaction conditions’, Europacat, Lyon, 1-6 Sept 2013.

Frenken, ‘Cobalt catalyst in action followed at high

on Advanced Electron Microscopy for Catalysis

pressures with STM and SXRD during hydrocarbon

and Energy Storage Materials. February 5th to

synthesis’, Symposium on Surface Science 2011,

8th 2012. Berlin – Germany

Baqueira Beret, Spain 6-12 March 2011.

NIMIC Final Report | Appendix A | Output

63. W.G. Onderwaater, M.E. Cañas-Ventura, A. Ofitserov, P.C. van der Tuijn, G. Verdoes, G.J.C van Baarle, R.C.T. Koehler, J.W.M. Frenken, ‘ReactorAFM TM; from vision to reality’, European Conference on Surface Science (ECOSS-27), Groningen, The Netherlands, August 29 September 3, 2010. 64. W.G. Onderwaater, M.E. Cañas-Ventura, A. Ofitserov, P.C. van der Tuijn, G. Verdoes, G.J.C van Baarle, R.C.T. Koehler, J.W.M. Frenken, ‘Reactor AFM; From vision to reality’, ECOSS27, Groningen, 29 August - 3 September, 2010

NIMIC Final Report | Appendix A | Output

Appendix A3 Other publications 1.

A. Ofitserov, G.J.C. van Baarle, Q. Liu, C.T. Herbschleb,

F.C. Tabak W.M. van Spengen, P.C. van der Tuijn,

‘Sub-Surface AFM’, Dutch SPM Day, Nijmegen, 18

as fast STM scanning elements’, Physics@FOM,

February 2011.

Veldhoven, Netherlands, 17-19 January 2012. 12. G.J. Verbiest, J.N. Simon, T.H. Oosterkamp, M.J. Rost,

J.W. Bakker, P.C. van der Tuijn, J.W.M. Frenken, ‘The ReactorSTM, high resolution, high pressure and

11. G.J. Verbiest, J.N. Simon, T.H. Oosterkamp, M.J. Rost,

J.W.M. Frenken, ‘An overview of solutions for MEMS

F.C. Tabak, W.M. van Spengen, J.W.M. Frenken, ‘MEMS

‘SubSurface AFM: towards nondestructive 3D micros-

high temperature’, Physics@FOM, Veldhoven, 17-18

systems applied in Scanning Tunneling Microscopes’,

copy’, Physics@FOM, Netherlands, Veldhoven, 18-19

February 2012.

Physics@FOM, Netherlands, Veldhoven, 18-19 January

January 2011.

2011. 2.

13. G.J. Verbiest, T.H. Oosterkamp, M.J. Frost, ‘sub surface

C.T. Herbschleb, P.C. van der Tuijn, M.E. Cañas-Ventura, D. Stoltz, I. Taminiau, Q. Liu, J.W.M. Frenken, ‘Reactor

F.C. Tabak, E.C.M. Disseldorp, P.C. van der Tuijn,

AFM Tip sample interaction in sub surface AFM’, MRS

SPM: Catalysis SPM research under Industrial condi-

G.H. Wortel, A.J. Katan, M.B.S. Hesselberth, T.H.

fall meeting, Boston USA, November 25-30 2012.

tions - an update on the STM’, NanoNed Meeting,

Oosterkamp, J.W.M. Frenken, W.M. van Spengen,

Eindhoven, The Netherlands, 28 November 2008.

‘MEMS for ultra-fast SPMs’, Physics@FOM, Veldhoven, Netherlands 19-20 January 2010.

reactor,’ Technisch Weekblad, 3 August 2008

C.T. Herbschleb, P.C. van der Tuijn, Q. Liu, A. Ofitserov, G.J.C. van Baarle, G. Verdoes, M.E. Cañas-Ventura, L.

14. H. Klomp, ‘Katalysator geeft geheimen prijs in nano

F.C. Tabak, E.C.M. Disseldorp, T.H. Oosterkamp, A.J.

15. J.W.M. Beenakker, ‘Distinct defects in collagen

Crama, J.W. Bakker, V. Navarro-Paredes, I. Taminiau,

Katan, M.B.S. Hesselberth, J.W.M. Frenken, W.M. van

micro-architecture underlie vessel-wall failure in

J.W.M. Frenken, ‘Live catalysts under industrial condi-

Spengen, ‘Need for speed (MEMS-based scanning

growing aortic abdominal aneurisms and aneurysms

tions imaged atomic resolution’, SPM-day, Eindhoven,

probe microscopy)’, Dutch Scanning Probe Microscopy

in Marfan Syndrome’, Dutch SPM Day, Eindhoven, 5

5 February 2010.

symposium 8/12/2008, Utrecht, The Netherlands, 2008.

February 2010.

E.C.M. Disseldorp, F.C. Tabak, G.H. Wortel, A.J. Katan, M.B.S. Hesselberth, T.H. Oosterkamp, J.W.M. Frenken,

G.J. Verbiest, ‘SubSurface AFM: Towards 3D Atomic Force Microscopy’, DPG conference 2010.

W.M. van Spengen, ‘Ultrafast MEMS-based scanning probe microscopy’, Scanning Probe Microscopy Day, Eindhoven, 5 February 2010.

16. J.W.M. Beenakker, B.A. Ashcroft, J.H.N. Lindeman, T.H. Oosterkamp, ‘Mechanical properties of the extra cellular matrix of the aorta studied by enymatic treatments’,

10. G.J. Verbiest, J.N. Simon, T.H. Oosterkamp, M.J. Rost,

Physics@FOM, Veldhoven, 17-18 January 2012.

‘Sub-Surface AFM’, Dutch SPM Day, Eindhoven, 5 February 2010.

NIMIC Final Report | Appendix A | Output

17. J.W.M. Frenken, ‘Live observations of catalysts

22. L. Mele, F. Santagata, G. Pandraud, B. Morana, J.F.

26. R. van Rijn, O. Balmes, M.E. Cañas-Ventura, M.

in action, using STM and X-rays: CW studiegroep

Creemer and P.M. Sarro, ‘MEMS nanoreactor: a new

Messing, A. Resta, D. Stoltz, D. Wermeille, R.

Spectroscopie en Theorie’, Lunteren, The Netherlands,

instrument for in-situ microscopy of nanomaterials

Westerström, K. Deppert, R. Felici, E. Lundgren, J.W.M.

January 26-27, 2009.

under realistic industrial conditions’, FHI trade fair Het

Frenken, ‘Spontaneous reaction oscillations on Pd

Instrument, Amsterdam, Sept. 28- Oct.1 2010 (best

nanoparticles and surfaces’, Physics@FOM, Veldhoven,

poster award) .

19-20 January 2010.

18. in-Situ Materials Characterization Across Spatial and Temporal Scales, Eds. A. Ziegler, J.W.M. Frenken, H. Graafsma, X.F. Zhang, Springer-Verlag, Chapter HighPressure STM (provisional title), in press 19. J.W.M. Frenken, ‘Atomic surface processes followed

23. M.E. Cañas-Ventura, D. Stoltz, C.T. Herbschleb, Q. Liu, I. Taminiau, W.G. Onderwaater, P.C. van der Tuijn,

Microtubules, Methods in Cell Biology 97, Microtubules

G. Verdoes, G.J.C. van Baarle, A. Ofitserov, J.W.M.

in vivo, chapter 24 eds. Cassimeris and Tran., 2010

Frenken, ‘ReactorSPM: Scanning probe microscopes

live with STM and X-rays: from catalysis to graphene

to “see” catalysts at work’, Physics@FOM, Veldhoven,

formation: FOM Institute for Atomic and Molecular

19-20 January 2010.

Physics (AMOLF)’, Amsterdam, The Netherlands,

20. J.W.M. Frenken, ‘In-situ STM and SXRD observations

28. S.B. Roobol, M.E. Cañas-Ventura, C.T. Herbschleb, Q. Liu, V. Navarro-Paredes, J.W. Bakker, I. Taminiau, W.G. Onderwaater, P.C. van der Tuijn, R.C.T. Koehler,

24. M. Rudneva, B. Gao and H. Zandbergen, ‘In-situ

February 8, 2010.

27. R.I, Koning, Cryo Electron Tomography of Cellular

A. Ofitserov, G.J.C. van Baarle, J.W.M. Frenken, ‘First

electrical measurements in TEM, Nederlandse

observations from the ReactorAFM: in-situ cataly-

Vereniging voor Microscopie (NVvM)’, Fall meeting

sis research at high pressures and temperatures’,

on active catalyst’, ACS Fall meeting, Philadelphia

2009, November 30th-December 1st, Amsterdam, the

Physics@FOM, Veldhoven, 17-18 January 2012.

USA, August 13-19 2012.

Netherlands. 29. S.B. Roobol, M.E. Cañas-Ventura, C.T. Herbschleb,

21. J.W.M. Frenken, ‘In situ studies of surfaces in Action’.

25. P. Puspitasari, P. Saputra, B. Morana, l. Mele, F.

Q. Liu, V. Navarro-Paredes, J.W. Bakker, I. Taminiau,

28th SAOG meeting, Fribourg Switserland, January

Santguta, J.F. Creemer, J. Westerweel and P.J.

W.G. Onderwaater, P.C. van der Tuijn, R.C.T. Koehler,

27th.

Kooyman, ‘Particle imaging and flow visualization

A. Ofitserov, G.J.C. van Baarle, J.W.M. Frenken, ‘Study

of nanoreactor’, NVvM Materials Science Meeting,

of the Fischer-Tropsch reaction with STM and XRD at

Eindhoven, 10 November 2011, poster.

industrial conditions’, Gordon Research Conferences “Catalysis”, New London, U.S.A., 27 June - 2 July 2010

NIMIC Final Report | Appendix A | Output

30. V. Navarro-Paredes, ‘Study of the Fischer-Tropsch reaction with STM and XRD at industrial conditions’, Casimir Spring School 2010, Arnemuiden, 14-16 June 2010. 31. V. Navarro-Paredes, S.B. Roobol, R. van Rijn, Q. Liu, O. Balmes, D. Wermeille, A. Resta, R. Felici, J.W.M. Frenken, ‘Fischer-Tropsch catalyst followed in action, This Week’s Discoveries’, Faculty of Science, Leiden University, Leiden, 6 March 2012. 32. V. Navarro-Paredes, S.B. Roobol, R. van Rijn,O. Balmes, D. Wermeille, A. Resta, R. Felici, J.W.M. Frenken, ‘In situ STM and SXRD during Fischer-Tropsch reaction’, Physics@FOM, Veldhoven, 17-18 January 2012.

NIMIC Final Report | Appendix A | Output

Appendix A4 Filed patents 1.

J.F. Creemer, G. Pandraud, and F. Santagata, ‘Method

P. Dona, H. Zandbergen, G. van Veen, ‘A holder assem-

of manufacturing a micro unit and a micro unit for

bly for cooperation in a environmental cell and a elec-

use in a microscope’, Application for an international

tromicroscope’, European Application No. EP12157055,

patent, 2003340, filed August 10, 2009.

US provisional 61/600,428.

D.J. Maas, M. Rudneva, E. van Veldhoven and H.W.

G.J.C. van Baarle, A. Ofitserov, I.A.J. Taminiau en R.

Zandbergen, ‘HIM Lamella preparation’, patent

van Rijn, ‘Gas analyzer and valve assembly for a gas

61/384035/US, 02-12-2010.

analyzer’, filed 2013.

G. van Veen, P. Dona, F. de Jong, J. Peters, ‘a micro

S. Osanto, R.G. Bertina, Y. Yuana, T.J. Oosterkamp,

reactor for observing particles in a fluid’, EP2322271A1,

B.A., Ashcroft, M.E. Kuil, J. Sonneville, ‘Methods for

US2011097706.

immobilizing microvesicles, means and methods for detecting them, and uses thereof’, WO2010072410. 7.

Q. Xu, G.F. Schneider, H.W. Zandbergen, M.Y. Wu, B. Song, ‘New lithographic method for the in-situ production of free-standig nanostrutures’, WO800550.

NIMIC Final Report | Appendix A | Output

Appendix A5 NIMIC PhD students en postdocs PhD students NIMIC

defense date

next positions

Postdocs NIMIC

end date

next positions

Kees Herbschleb

April 2011

ASM

Dunja Stoltz

June 2009

Assistant Prof. Univ. Stockholm

Sander Roobol

2014

Martha Cañas Ventura

April 2011

Evonik Industries GmbH

Qian Liu

2014

Søren Vendelbo

April2013

pending

Indra (Pita) Puspitasari

2013

Gregory Pandraud

Dec 2011

TU Delft, Dimes

Jan Willem Beenakker

June 5, 2012

LUMC

Roman Koning

2011

LUMC

Bruno Morana

2013

Brian Ashcroft

February 2011

Arazona State University, USA

Gerard Verbiest

October 2013

Cveta Tomova

2010

Leica

Maria Rudneva

January 2013

Postdoc TUD

Bram van den Broek

October 2010

NKI-AvL

Bo Song

2014

Luigi Mele

October 2011

FEI

Femke Tabak

June 2013

pending

Richard van Rijn

July 2013

LPM and ANL

Rik Mom (one year NIMIC)

January 2017

Christian Elkjaer (one year NIMIC)

NIMIC Final Report | Appendix A | Output

Appendix A6 PhDs theses 1.

K. Herbschleb, ‘Imaging catalyst under realistic condi-

tions’, Leiden University. 10 May 2011. Promotor: Prof.

M. Rudneva, ‘In situ electrical measurements in transmission electron microscopy’, Delft University of

dr. J.W.M. Frenken, ISBN: 978-90-8593-098-3

Technology, 16 January 2013. Promotor: Prof.dr. H.W. Zandbergen, ISBN 978-90-8593-147-8

J.W. Beenakker, ‘Unravelling the collagen network of the arterial wall’, Leiden University, 5 June 2012.

F.C. Tabak, ‘Towards high-speed Scanning Tunneling

Promotor: Prof.dr.ir. T.H. Oosterkamp, Co-promotor:

Microscopy’, Leiden University, 6 June 2013. Promotor:

Dr. J.H. Lindeman, ISBN: 978-90-8593-123-2

Prof.dr. J.W.M. Frenken, Co-Promotor: Dr.ir. W.M. van Spengen, ISBN: 978-90-8593-160-7

NIMIC Final Report | Appendix A | Output

Appendix B, Deliverables

The tables in this appendix list the deliverables that were defined

stage of the program. The deliverables are grouped according to

after the midterm review of the NI M I C program, i.e. after an initial

the four Work Packages, in which the program was structured.

ensemble of deliverables had already been reached. This second

The table indicates the status for each deliverable and it provides a

set of deliverables reflects the emphasis on valorization in this

brief, additional remark, where appropriate.

WP1, Live nano-imaging of processes under catalytic conditions Deliverable

Status

ReactorSTM and AFM: development of two complete setups,

done

Remarks

including ultrahigh vacuum system, sample handling, preparation and characterization, integrated reactor&STM/AFM inserts, STM and AFM electronics and control systems ReactorSTM and AFM: development of the required gas mixing and flow

done

regulation cabinet and the gas analysis system as separate, stand-alone

partly realized within one of the extra NIMIC-finalphase projects

units ReactorSTM: commercial version of complete ReactorSTM setup with gas

done

system

one complete system sold by LPM; also several copies sold by LPM of the related ReactorSXRD setup

ReactorAFM: commercial version of complete ReactorAFM setup

on hold

Scientific results: demonstration experiments on catalyst structure

done

not ready for market: prototype not yet considered sufficiently stable and easy to use

(restructuring) during oxidation and reduction catalysis Scientific results: hydrogen-driven desulfurization of thiophene

partly realized within one of the extra NIMIC-finalphase projects

in progress

preparations and test measurements done; two

molecules, obtained both on flat surfaces (ReactorSTM) and on supported

extra projects (one within NIMIC, the other outside)

nanoparticles (TEM)

devoted to reach this deliverable during NIMIC fadeout in 2013/2014

NIMIC Final Report | Appendix B | Deliverables

WP2, Live nano-imaging of processes under biological and bio-medical conditions Deliverable

Status

Remarks

Liquid nanoreactors: operational prototypes for biological use (silicon-

done

all-glass based version added as extra deliverable

done

unfortunately, vitrification of cell structure inside

based and all-glass based), including peripheral tools and protocols Correlative microscopy: prototype of correlative optical microscopy and cryo-electron-tomography, including plunge freezing Correlative microscopy: combination of 2-photon confocal optical

nanoreactors is hard to achieve done

microscopy and atomic force microscopy Scientific results: demonstration experiments on cell migration

done partly

optical observations of cell migration have been made with the glass nanoreactors; these nanoreactors were not yet fit for TEM experiments

Scientific results: relation between structure and mechanical behavior of

done

various tissues (AFM) Scientific results: chromatin organization (sub-surface AFM and 2-photon multifocal optical microscopy)

done partly

sub-surface AFM observations were not carried out (see WP4)

NIMIC Final Report | Appendix B | Deliverables

WP3, Live nano-imaging of materials processes Deliverable

Status

Gas nanoreactors: family of operational prototypes of clean and easy-to-

done

Remarks

use TEM nanoreactors for application to model catalysts exposed to hot, flowing, high-pressure gas mixtures (WP1), including peripheral tools (partly in WP1 and WP4) Gas nanoreactors: at least one of the above configurations should lead to a

in progress

commercial prototype (product)

prototype for commercial surface micromachined nanoreactor completed at DIMES; in one of the extra NIMIC-final-phase projects a prototype for a commercial bonded version is under development at Lionix/ FEI

TEM sample holders for materials processes: operational holders for

done

the live observation of electromigration and of deposition and growth phenomena Scientific results: demonstration experiments on electromigration of metals (TEM, sub-surface AFM), of the sculpting of graphene (TEM) and of

done partly

sub-surface AFM observations were not carried out (see WP4)

the deposition of gold and platinum on graphene (TEM)

NIMIC Final Report | Appendix B | Deliverables

WP4, General instrumentation for live nano-imaging Deliverable

Status

ETEM: improved prototype for environmental transmission electron

done

Remarks

microscope (ETEM) with gas in- and outlets TEM holders: commercial prototypes of versatile and clean TEM holders

done partly

next to FEI prototypes, also the Delft spin-off,

plus auxiliary equipment (loading tools, gas handling, vitrification, heating

DENSsolutions is now in the market of special-

capabilities, etc.) for various types of nanoreactors (WP1, WP2, WP3)

purpose TEM holders; no commercial prototype yet for bio-holder (WP2)

High-speed STM: test results and set of design rules for (MEMS-based and

done

too early for commercial prototype

done

in addition to the instrument also a full

piezo-based) high-speed STM, including the potential development of a commercial prototype instrument, based on this technology Sub-surface AFM: operational sub-surface atomic force microscope

understanding has been acquired of its contrast mechanism; this part of the work has been so complex that there was no time left for the applications in WP2 and WP3 CMOS camera: commercial version of CMOS camera for high-speed,

done

sensitive, low-dose electron microscopy

the Falcon camera is now in service at several customer locations; new generation is under development

Scientific results: demonstration experiment on atomic-scale step

done partly

step-fluctuation experiments were not carried out as

fluctuations (high-speed STM) and evaluation of the performance of the

the instrumentation development had taken more

CMOS camera

time than anticipated

NIMIC Final Report | Appendix B | Deliverables

Appendix C, Composition of N I M I C

NIMIC Directors

Prof.dr. Hans-Joachim Güntherodt (University of Basel,

2.4 Bio-SPM, Prof.dr.ir. Tjerk Oosterkamp (LU)

Scientific Director: Prof.dr. Joost Frenken (LU)

Switzerland)

2.5 Sub-surface SPM imaging, Prof.dr.ir. Tjerk Oosterkamp

Business Director: Dr.ir. Richard van der Linde (TUD)

Prof.dr. Jacques Joosten (DSM and DPI)

2.6 E-cadherin and cadherin-11 and their role in cancer

N I M I C Work packages and projects

2.7 Chromatin organization in the cell nucleus, Prof.dr.ir.

NIMIC Secretariat Mrs. Maria Roodenburg-van Dijk (TUD)

(LU)

Prof.dr. Ib Chorkendorff (Technical University of Denmark)

migration, Prof.dr. Peter Peters (NKI-AvL) WORK PACKAGE 1:

Tjerk Oosterkamp (LU)

NIMIC Board

Live nano-imaging of processes under catalytic conditions

Prof.dr.ir. Herre van der Zant (TUD, chair)

Leader: Dr. Bart Nelissen (Albemarle)

WORK PACKAGE 3:

Prof.dr. Eric Eliel (LU)

1.1 Reactor-SPM, Prof.dr. Joost Frenken (LU)

Live nano-imaging of materials processes

Dr. Frank de Jong (FEI)

1.2 Oxidation/reduction reactions, Dr. Patricia Kooyman

Leader: Prof.dr. Henny Zandbergen (TUD)

Dr. Gertjan van Baarle (LPM) Dr. Eelco Vogt (Albemarle)

(TUD) 1.3 Hydrotreating of oil, Dr. Patricia Kooyman (TUD)

3.1 Realization of a set of nanoreactors for a wide range of specifications, Dr. Fredrik Creemer (TUD) 3.2 Electromigration, Dr. Marcel Rost (LU)

Dr. Charlotte Clausen Appel (Haldor Topsøe) Prof.dr. Hans Tanke (LUMC)

WORK PACKAGE 2:

Dr. Henri van Luenen (NKI-AvL)

Live nano-imaging of processes under biological and

3.3 Film growth followed in-situ by TEM, Dr.ir. Frans Tichelaar (TUD)

biomedical conditions NIMIC Strategic Advisory Committee (SAC)

Leader: Prof.dr.ir. Bram Koster (LUMC)

WORK PACKAGE 4:

Dr. Kees van der Wiele (retired from Albemarle, chair)

2.1 Nanoreactors for biological use, Prof.dr. Henny

General instrumentation for live nano-imaging

Prof.dr. Hans Hofstraat (Philips)

Zandbergen (TUD)

Prof.dr. Richard Henderson (Cambridge University, UK)

2.2 Correlative microscopy, Prof.dr.ir. Bram Koster (LUMC)

Prof.dr. Joachim Mayer (RWTH Aachen, Germany)

2.3 CMOS camera (project redefined as 4.5), Dr. Gerard

Leader: Dr. Gerard van Veen (FEI) 4.1 System integrity and system engineering, Ir. Mathijs de Moor (FEI)

van Veen (FEI)

NIMIC Final Report | Appendix C | Composition of N IMIC

4.2 Sample holders and sample loading for nano-reactors in TEM, Dr. Gerard van Veen (FEI) 4.3 Video-SPM, Prof.dr. Joost Frenken (LU) 4.4 Sub-surface SPM, Dr. Marcel Rost (LU) 4.5 CMOS camera (originally project 2.3), Dr. Gerard van Veen (FEI) EXTRA: N I M I C -final-stage projects (managed within Work Package 1) E1 Bonded gas nanoreactors, Dr. Gerard van Veen (FEI) E2 ReactorSPM: new demonstration experiments – seeing the catalyst and seeing the catalysis, Prof.dr. Joost Frenken (LU) E3 A fast high-resolution gas analysis system with high-pressure/low-flow compatible sampling system, Dr. Gertjan van Baarle (LPM)

NIMIC Final Report | Appendix C | Composition of NIMIC

of the seven SmartMix programs that have been granted in 2007. The goal of NIMIC has been to use electron microscopy and scanning probe microscopy techniques to make physical, chemical and biological processes visible that are taking place on the atomic and molecular scale. Novel technologies have been developed to deliver the first, direct ‘atomic look’ on highly relevant, practical phenomena under realistic and relevant process conditions. NIMIC has been a six-year program that has run from 1 July, 2007, to 1 July, 2013. The NIMIC consortium consisted of the following eight partners from the public and private domains: Delft University of Technology (administrative seat of NIMIC), Leiden University, FEI Company BV, Leiden Probe Microscopy BV, Albemarle Catalysts Company BV, Leiden University Medical Centre (LUMC), Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI/Av L), and Haldor Topsøe A/S. The total NIMIC budget of 25 M€ contained a 14 M€ grant from SmartMix and 11 M€ in in-kind and cash contributions from the individual partners in the program. This report reflects the results of this 7 year public private collaboration. www.realnano.nl

N I M I C • F I N A L R E P O R T • SM A R T M I X P R O G R A M 2007-2013 • PR O J E C T C O D E : SSM06002

NIMIC, i.e. Nano-Imaging under Industrial Conditions, has been one