Entirely new forms of microscopy
Submitting Institution
Lancaster UniversityUnit of Assessment
PhysicsSummary Impact Type
TechnologicalResearch Subject Area(s)
Physical Sciences: Atomic, Molecular, Nuclear, Particle and Plasma Physics, Other Physical Sciences
Chemical Sciences: Physical Chemistry (incl. Structural)
Summary of the impact
Basic research combining scanning probe microscopy with thermal,
spectroscopic and chemical
analysis has enabled the development of powerful, entirely new forms of
analytical microscopy.
Commercialisation of instruments for micro-thermal analysis began by TA
Instruments, in 1998,
based on four patents, followed by a Lancaster start-up company Anasys Ltd.
These instruments
have since been extensively used in multidisciplinary applications by
scientific industry and
government laboratories. Anasys has sold over 100 units of these nanoscale
thermal analysis
instruments (total turnover £3M) and many leading polymer industries,
research institutes and
academic programs worldwide are now users of this technology.
Underpinning research
Fundamental research led by H.M. Pollock and A. Hammiche during the
mid-1990s in Lancaster
University Physics Department into the thermal properties of materials on
the nanoscale resulted in
the development of a cantilever with an ultra-miniature resistive element
on its tip, which can act
either as a temperature sensor or as a point-like heat source. Pollock and
Hammiche were the first
in the world to develop the ability to simultaneously deposit thermal
energy and measure
temperature changes on a sub-micron scale. This breakthrough was expanded
into a new generic
scanning thermal probe microscopy (SThM) technology, where purely thermal
modes of imaging
are complemented with localised analysis. For the first time individual
regions of a solid sample
could be selected by means of surface or even sub-surface imaging to
combine spatial
discrimination and chemical fingerprinting using calorimetry,
thermomechanometry, infrared
spectroscopy and pyrolysis mass spectrometry. The outcome was a powerful
new form of
analytical microscopy.
Building on the results of their basic research into the interaction of
solid surfaces with thermal
stimulus and thereafter on the realisation that this could be combined
with the precision of the
scanning thermal probe, academic findings were disseminated in high impact
scientific journals,
web pages and specialist conferences. The 1st International Workshop on
Spectral Diagnostics
(2007) proved to be a landmark event pointing the way forwards for
clinicians to make use of
spectroscopic instrumentation. From the beginning the research was carried
out in close
collaboration with chemists (D. Hourston, Loughborough University and M.
Reading, UEA),
biologists at Lancaster (N.J. Fullwood & F. Martin) and more recently
with clinicians in the NHS (P.
Martin-Hirsch, Consultant, Royal Preston Infirmary). Consequently, new
applications in polymer
blends, pharmaceuticals and biomaterials were developed.
The research was funded (> £2.1M) by EPSRC, BBSRC and EU and attracted
strong industrial
interest throughout, which led to instrument development and subsequent
commercialization by TA
Instruments and Anasys Ltd. Since 1995 four patents were successfully
filed, three of which were
initially assigned to TA Instruments. In March 1998, the "Micro-thermal
Analyser" (marketed by TA
Instruments Co., based upon this research) was awarded the PittCon Gold
Award for the best new
product at PittCon '98 (the world's largest annual scientific instruments
conference — 3000 exhibits,
25000 attendees), as judged by a panel of editors of the leading
international scientific
instrumentation journals. The instrument subsequently won the R & D
100 award in September
1998 and received a Design Council "Millennium Award" in 1999 following
its exhibition in the
Millennium Dome.
In 2005 a Lancaster Start-Up company "Anasys Instruments" was formed,
having negotiated the
re-assignment of the first three patents from TA Instruments to Anasys.
Since then Anasys
Instruments has developed and introduced multiple major award-winning
technologies: nanoscale
thermal analysis (nano-TA™), transition temperature microscopy (TTM™),
AFM+ thermal analysis
(afm+™), and AFM+ IR Spectroscopy (nanoIR™). The afm+ was a 2007/2008
R&D 100 Award
winner, and the nanoIR won the honour in 2010 as well as a Microscopy
Today Innovation Award.
References to the research
(1) H. M. Pollock and A. Hammiche, J Phys D: Appl Phys 34, R23-R53
(2001), Micro-thermal
analysis: techniques and applications.
Describes the underpinning research work performed at Lancaster leading
to instrument
development, (144 citations).
(2) A Hammiche, H M Pollock, M Reading, M Claybourn, P Turner and K
Jewkes, Applied
Spectroscopy 53, 810-815 (1999). Photothermal FTIR spectroscopy: a step
towards FTIR
microscopy at a resolution better than the diffraction limit.
Describes a technique for near-field infrared spectroscopy with
sufficiently high spatial resolution
for chemical analysis of sub-micron-sized volumes to be performed. Has led
to further patents,
commercial application, and biomedical research on tissue samples at the
near-single-cellular
level.
(3) F L Martin and H M Pollock, Oxford Handbook of Nanoscience and
Technology 2 (A V Narlikar
and Y Y Fu, eds.), pp. 285-336 (2010), Microspectroscopy as a tool to
discriminate nano-molecular
cellular alterations in biomedical research.
This O.U.P. book chapter is a keynote review with high citations and a
standard reference in the
field.
(4) Jemma G. Kelly, Júlio Trevisan, Andrew D. Scott, Paul L. Carmichael,
Hubert M. Pollock, Pierre
L. Martin-Hirsch and Francis L. Martin, Biospectroscopy to metabolically
profile biomolecular
structure: a multi-stage approach linking computational analysis with
biomarkers. J Proteome Res.,
10(4), pp 1437-1448 (2011)
This is a keynote article, published in a journal with high citation
index (5), and will be a standard
reference in the field for many years.
(5) Discrimination of human stem cells by photothermal microspectroscopy,
O Grude, T Nakamura,
A Hammiche, A J Bentley, F L Martin, H M Pollock, S Kinoshita and N J
Fullwood, Vibrational
Spectroscopy 49, 22-27 (2009).
One of the first examples of the use of nano-IR in biomedical research.
(6) FTIR micro-spectroscopy identifies symmetric PO2- modifications as a
marker of the putative
stem cell region of human intestinal crypts, Michael J. Walsh, Tariq G.
Fellous, Azzedine
Hammiche, Wey-Ran Lin, Nigel J. Fullwood, Olaug Grude, Fariba Bahrami,
James M. Nicholson,
Marine Cotte, Jean Susini, Hubert M. Pollock, Mairi Brittan, Pierre L.
Martin-Hirsch, Malcolm R.
Alison and Francis L. Martin, Stem Cells 26, 108-118 (2008) Includes some
nano-IR data,
published in a journal with a high citation index (7.9).
Details of the impact
In localised calorimetry and thermomechanometry, the probe heats any
microscopic feature of
interest so that events such as glass transitions, crystallisation,
melting and decomposition are
induced and detected. This capability transformed SThM into a powerful new
form of analytical
microscopy with wide-ranging applications. Meanwhile, photothermal nano-IR
is used to obtain
infrared spectra from sub-micron sized regions, and improved methods
involving chemometrics
and/or fuzzy logic enable detection of minute compositional differences
between otherwise
identical samples.
The direct beneficiaries of our research include two companies who have
successfully developed
and sold instruments based on our high spatial resolution near-field
thermal methods for analysis
and characterization. The first range of instruments, namely the
"Micro-thermal Analyser", was
commercialized by TA Instruments Inc. (New Castle, Delaware USA). An
improved version, the
"Nano-TA", was subsequently developed by our start-up company Anasys
Instruments. The
second range of instruments (nano-IR, Anasys) uses the same type of
probes, combining thermal
microscopy with infrared spectroscopy to yield a new technique, namely
nano-infrared
microspectroscopy.
The research organisation TNO in the Netherlands has used the micro-TA
instrument extensively
for the microthermal analysis of durability and to determine glass
transition temperatures in
polymers. Subsequently, Borealis who are a leading provider of chemicals
and plastics used the
instrument for quality control of polypropylene to detect inclusions and
impurities and to investigate
customer claims in the development of polymer films and packaging for the
healthcare and
electronics industries. Our research has also led to development of
high-resolution biomedical
imaging techniques applicable to tissue engineering; drug testing and
discovery for amyloid
diseases (e.g., Alzheimer's disease) and DNA studies. For detection of
minute compositional
differences between otherwise identical samples, our research has also
helped develop improved
chemometrics and/or fuzzy logic.
The wider beneficiaries include a variety of scientific and industrial
end users of our technology.
Micro-thermal analysis is now being widely used commercially to visualize
the spatial distribution of
phases, components, and contaminants in polymers (Kimberly Clark),
pharmaceuticals (Molecular
Profiles Ltd., 3M Healthcare, Pfizer, AstraZeneca), foods, biological
materials and electronic
materials, nanoscale spectroscopy, electronic and heat transport
properties of novel
macromolecular systems, (such as carbon nanotubes), manipulations of atoms
and macro-molecules
into nanostructures; development and investigation of submicron- and
nano-structures
of novel inorganic and organic semiconductor materials. For example, Tom
Eby of Kimberly Clark
Corporation, states that "`Reverse engineering based on IR is an
important application in most
industrial labs and the spatial resolution breakthrough of the AFM-IR
technique now enables this
for a wide range of materials with sub-micron features.'' Being
based upon extensive basic
nanophysics research in novel materials, our cross-disciplinary research
was also fundamental to
the development of non-invasive scanning techniques for biological and
biomedical applications.
These include studies of bio-chemical processes in plant cells; for
example, the Micro-TA has been
used to help Syngenta develop a better model for understanding herbicide
interactions with leaf
surfaces. Meanwhile, work by Molecular Profiles Ltd. on solid dispersion
formulations using the
NanoTA in collaborations with Nottingham University and Janssen
Pharmaceuticals has led to the
development of formulations for poorly soluble drugs (such as the
anti-AIDS drug etraviri, now in
the product Intelence®.
Sources to corroborate the impact
(1) Factual statement by key user at Nottingham University which
articulates applications in
Pharmacy and healthcare together with industrial users (-available on
request)
(2) Report from Kimberley Clark Corporation : Spectroscopy Europe 24(3)18-21,
(2012)
(3) List of references (10 papers) provided by TNO describing different
aspects of microthermal
analysis of polymers (-available on request)
(4) Paper from Borealis describing identification of inclusions in
polymers (-available on request)
(5) Nano-TA instrument developed by Anasys Instruments based on Lancaster
research wins the
R&D 100 award. http://www.rdmag.com/Awards/RD-100-Awards/2007/09/RD100-Awards-Bridging-The-Gap-With-AFM/
validates that the instrument brings new capability and measures
both thermal and nanoscale properties quantitatively.
(6) A further Anasys instrument (Nano-IR) derived from Lancaster research
won the 2010 R&D
award http://www.rdmag.com/Awards/RD-100-Awards/2010/08/AFM-gains-chemical-composition-power/
and enables chemical analysis of samples down to 100 nm in spatial
resolution, an
improvement of up to two orders of magnitude over conventional
transmission IR micro-spectroscopy.
Patents
(7) "Method and apparatus for performing localized thermal analysis and
sub-surface imaging by
scanning thermal microscopy" US 6,491,425 & US 6,095,679,
(8) "Method and apparatus for high spatial resolution spectroscopic
microscopy" US 6,260,997,
(9) " Method and apparatus for localized dynamic mechano-thermal analysis
with scanning probe
microscopy" US 6,200,022
(10) "Microspectroscopy Apparatus and method" , Reading, Montagu-Pollock,
Wood,
WO2,011,007,168