Multimodal Spatially Resolved Near-Field

Scattering and Absorption Spectroscopy

Edwin Ostertaga, Tobias Merza and Rudolf W. Kessler*
Reutlingen Research Institute, Reutlingen University, Alteburgstr. 150, 72762 Reutlingen, Germany
a
contributed first authorship

ABSTRACT

Far-field microscopy techniques are routinely used for the visualization of biological systems, but are limited according
to Abbe`s criteria to about λ/2. The objective of this work is to integrate a solid immersion lens (SIL) as a near-field
probe into a standard microscope spectrophotometer in order to perform polychromatic illumination near-field
microscopy as well as near-field spectroscopy. The SIL concept can achieve a higher resolution than expected by the
increase of the numerical aperture. Even with a tip diameter of 700nm and a tip point angle of 130° the lateral resolution
is in the range of about 30 nm, therefore overcoming the tradeoff between the resolution and intensity restrictions in
aperture limited SNOM probes. In this paper the optical setup of the system is described and some images of biological
samples on a nanoscale with high contrast are presented.

Keywords: scanning near-field optical microscopy, spectroscopy, solid immersion lens

1. INTRODUCTION
1.1 Resolution in microscopy
Accordingly to Abbe’s theory, the spatial resolution ∆x of far-field microscopy is limited by the diffraction behavior of
light waves: ∆ with λ corresponding to the utilized wavelength, n to the refraction index between the
objective and the specimen, and sinα to the half aperture angle of the optical system. The term n sinα is also described as
the numerical aperture (NA).1 The resolution of a microscope can be improved by several factors, e.g. using shorter
wavelengths or increasing the aperture of the lens, for example by immersion technology. Very high indices of refraction
can be achieved through a solid immersion lens (SIL). When high refractive index materials like ZrO2 or GaP are used,
the lateral resolution of a microscope can be reduced down to about 100 nm. This effect has been described as numerical
aperture increasing lens (NAIL) technique. A separation of the near-field part from the background signal improves the
resolution to 30 nm.2
Far-field microscopy techniques are routinely used for the visualization of biological systems. The advantages of
fluorescence microscopy are its high sensitivity together with the highly specific fluorescent markers. Strong efforts have
been made to increase the resolution of microscopy further by introducing confocality. Light of a point source
illuminates a very small region of a sample, and a point detector collects light from that small area. The light source and
the detector are scanned synchronously across the image plane.3
The spatial limitation for illumination and detection by a pinhole enables an optical sectioning because the out-of-focus
light is eliminated. A confocal microscope has a lateral resolution up to 1.4 times compared to a conventional
microscope and suppresses fogginess which marks an important improvement for the investigation of living samples.
The resolution can be further increased through pin-hole filtering in laser-scanning microscopy or by non-linear optical
processes (stimulated emission depletion, STED), resulting in a resolution up to λ/40 in fluorescence microscopy.4

*rudolf.kessler@reutlingen-university.de; phone ++49 7121 271 2010; fax ++49 7121 271 2013

Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications VIII, edited by Alexander N. Cartwright,
Dan V. Nicolau, Proc. of SPIE Vol. 8231, 82310A · © 2012 SPIE · CCC code: 1605-7422/12/$18 · doi: 10.1117/12.909086

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Thus many biological structures and processes can be visualized and analyzed in three dimensions well below the
diffraction limit, this is also the case with STED. However, these techniques work with high light intensities and suffer
from serious damage of a living cell.
1.2 From far-field to near-field microscopy
In 1982 Binning and Rohrer introduced the Scanning-Tunneling-Microscope (STM).5 With the piezo-scanner-technology
for precise positioning of the sample, structures even on an atomic scale could be resolved. The first contrasted image
with atomic resolution was generated by using an electron-tunneling current. In subsequent years the scanning technique
was expanded through a wide variety of detection methods, for example, the measurement from atomic force microscopy
(AFM) or the depiction of magnetic fields from magnetic force microscopy (MFM).6 By using these techniques, the
lateral resolution is exclusively dependent on probe geometry.
The combination of optical light microscopy with scanning probe technology first appeared in the mid 1980’s. Both
topographical and chemical information can be obtained from sample surfaces with this method. The principle of using a
very small aperture to bypass the diffraction limit has already been recognized in 1928 during the correspondence of
Synge and Einstein.7 His idea was to use a light source smaller than the wavelength of the light and with it, go as near as
possible to the surface of the sample, illuminating the sample in the near-field while detecting the information in the far-
field. For the light source, an arc lamp was placed behind an opaque metal film with a very small hole measuring ca. 100
nm. A major problem at that time in the implementation of this technique was, however, the difficulty in the exact
positioning of the light source over the sample. 28 years later, independent from Synge, J.A. O’Keefe identified that,
through the use of a small aperture the diffraction limit could be bypassed.8 However, bypassing the resolution limits in
the field of microwaves was first demonstrated by Nicholls in 1972, by mapping a grid of radiation with a wavelength of
3 cm.9 With this, an achieved resolution of λ/60 in the x-direction and λ/20 in the y-direction could be confirmed. 12
years later Pohl et al. and Lewis et al., independent of each other, discovered that the idea also works in a visible
wavelength range using a near-field microscope. Both groups realized a resolution of λ/20.10;11
Various implementations of Synge´s idea of confining the light and forcing it to a sub-wavelength aperture have been
made available but they still have some drawbacks.12 Fundamental problems are low transmission efficiency through the
probe, the highly sensitive sample-probe distance regulation to protect the fragile tip and the bad reproducibility of the
tip-aperture. To distinguish the near-field signal from the far-field illumination, an expansion of the near-field portion by
a factor of about 103 or an efficient suppression of the background is necessary. In order to receive a high spatial
resolution in microscopy, high spatial frequencies must be detected. However, these spatial frequencies are to be
described through the non-propagating components and not attained in the far-field. The only possibility to detect near-
field components is in the conversion into propagating fields. The principles for the development of near-fields can also
be applied to their conversion. Through the introduction of variable disturbance in the field, the field becomes scattered,
absorbed, or can further propagate into a dielectric medium.13
The possibility of obtaining optical information about the substrate below the diffraction limit has been exploited in
many areas of science. Thereby e.g. fluorescence emission, refractive index differences or variations in the scattering of
light are determined.14 In recent years, these parameters in near-field microscopy were not only used for imaging, but
also e.g. the wavelength dependence for the characterization of substrates included in the near-field.15;16;17 Some
application areas of the optical near-field are optical data storage, optical communications technology, near-field
microscopy and spectroscopy (fluorescence spectroscopy) in cell biology, and near-field lithography. For the application
in cell-biology, the focus lies on the localization and characterization of individual proteins or molecules using common
fluorescence markers.18;19;20 Label-free diagnostics is already being carried out for early recognition of skin cancer using
two-photon microscopy or Raman spectroscopy. Recently, a non-invasive probe capable of both morphological and
biochemical characterization of skin cancer based on Raman spectroscopy has been announced.21 Likewise, some
applications of IR-spectroscopy for the analysis of histological slices are known.22;23 A marker-free characterization with
the use of near-field microscopy on the basis of spectral properties has not yet been specified.
1.3 Motivation and goals
A key element in near-field optical microscopy is the transducer, the translation of near-field information into far-field
information. Despite the development of different probe concepts, near-field microscopy still lacks a reasonable market
penetration. One reason is the limitation in the manufacturing of the probe. In addition, the interaction between the probe
and the substrate is still not yet well understood, making the interpretation of the recorded information difficult.

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In recent years, a concept of a new scanning probe was developed and published by Ghislain et al.24 In this development,
monochromatic laser light or polychromatic light is injected through an objective (50 x 0.55 NA) in a lens and recorded
by a photodetector. This method yields a resolution of < 150 nm. The SIL concept assures an improvement of the signal-
to-noise (S/N) ratio in comparison to aperture-limited systems due to the high transmission through the lens. A SIL probe
producing a spot size of about 100 nm transmits about half (50%) of the optical power. By comparison, a metal-coated
fiber-probe with a 100 nm aperture transmits only about 10-5 (0.001%). The high S/N ratio is a prerequisite to carry out
near-field optical spectroscopy.
The objective of this work is to integrate a solid immersion lens as a near-field probe into a standard microscope
spectrophotometer in order to perform polychromatic illumination near-field microscopy as well as near-field
spectroscopy. It will be demonstrated that the SIL concept can achieve a higher resolution than just expected by the
increase of the numerical aperture. Even with a tip diameter of 700 nm and a tip point angle of 130° lateral resolution is
in the range of about 30 nm, therefore overcoming the tradeoff between the resolution and intensity restrictions in
aperture limited SNOM probes. In this paper we will describe the optical setup of the system and we will present some
images of biological samples imaged on a nanoscale with high contrast. The spectroscopic part will be presented in the
extended version of this paper.

2. NEAR FIELD IMAGING AND SPECTROMETER SYSTEM

2.1 Optical setup
The construction of the near-field microscope for wavelength dependent measurements consists of two modules: a
universal microspectrophotometer (UMSP 80 from Carl Zeiss) and a near-field unit with a scanning probe microscope
(SPM from Bruker Nano) for keeping the solid immersion lens and moving the sample (Figure 1). A detailed description
is given in.25

Figure 1. Schematic diagram of the near-field microspectrophotometer consisting of a universal microspectrophotometer

UMSP 80 (Carl Zeiss) and a scanning probe microscope MultiMode (SPM, Bruker Nano). The solid immersion lens is
mounted in a bracket and positioned between the microscope objective and the sample. The drawing top left depicts two

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 different illumination angles onto the SIL for generating two types of contrast: a) Reflectance-Scanning Near-Field
Optical Microscopy mode (R-SNOM) and b) Photon-Tunneling Near-Field Optical Microscopy mode (P-SNOM),
leading to a contrast inversion of the image.

The UMSP allows spectroscopic measurements in reflection and transmission from 200 nm to 2500 nm. With aperture
and illumination field diaphragms, a Köhler illumination can be realized.26 In spectroscopy, the illumination field
diaphragm is adjusted to the size of the measuring field diaphragm in order to avoid scattered light. The near-field unit
comprises three components: the base control unit, the scanner with z-axis motor for the approach of the sample to the
probe and the scan head. The whole system is built in a rotary table. Figure 2 shows the configuration of the scanner
head.

Objective
Photodiode

SIL

SIL in Bracket
Laser Diode

Piezo Scanner

Rotary Table

Figure 2. The figure shows the scanner head for optical near-field investigations. The piezo scanner is fixed into a rotary
table in which the detection unit is attached by two springs. Four magnets on the detection unit attach the SIL holder. In
order to register the deflection of the cantilever, the reflection of a laser diode is detected through the photodiode. The
laser-point can be positioned on the photo diode by using a mirror (for more details see25;27).

A solid immersion lens of ZrO2 acts as an apertureless near-field probe. The SIL probe has a hemispherical upper surface
with a diameter of 1.00 mm and a lower surface with a conically sanded tip forming the scanning probe. The tip diameter
is determined to be 700 nm by scanning electron microscopy. The tip has a point angle of 130°. The surface inaccuracy
of the hemisphere is lower than λ/4. The focused spot on the sample surface generates an evanescent wave where the
amplitude decays exponentially with distance from the SIL. The conical tip on the bottom of the SIL ensures that the
sample is positioned within the near-field of the SIL probe. The specimen perturbs the evanescent wave and a
microspectrophotometer records the characteristics of the light. The SIL is fixed in a flexible metal foil cantilever
operated in SPM contact mode. The cantilever deflection is monitored with a beam deflection laser permitting precise
control of tip-sample forces and separation. The beam deflection setup runs in a force feedback loop to maintain the tip-
sample distance within the near-field during scanning the sample underneath the fix SIL tip in a raster pattern to generate
optical data.

Depending on the illumination angle of the incident light onto the SIL, different near-field contrast modes can be
achieved (figure 1 top left). The Reflectance-Scanning Near-Field Optical Microscopy (R-SNOM) mode is realized with
illuminating the SIL within the critical angle. The Photon-Tunneling Near-Field Optical Microscopy (P-SNOM) mode is

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achieved by illuminating the SIL below the critical angle. Thus a contrast inversion of the near-field image takes place
due to tunneling of photons into the substrate.

The design of the SIL and the integration in a microspectrophotometer allows to perform multi-modal spectroscopy as a
tool to separate marker free multi-dimensional information. The term “multi-modal” in this context does not only mean
to combine the information of different spectral regions (e.g. UV/Vis and NIR or Raman or fluorescence), but also to
combine the information of different optical set-ups and contrast modes.

2.2 Spatial resolution

The lateral resolution of an imaging system can be obtained in different ways. The definition is based on the smallest
distance which can be resolved with confidence. In the case of a single point, the intensity profile of this point (point
spread function, PSF) can be used to estimate the resolution by the full width at half maximum (FWHM). The same rules
apply to lines (LSF, line spread function) at the distance between 12% and 88%. Near-field images are point by point
maps of the interaction e.g. scattering, absorption or change in refractive index between the probe and the substrate.
Every image is the sum of interactions with the probe. Depending on the substrate interaction the influences in the
recorded image vary.

The test pattern BAM-L002, kindly provided by the Federal Institute for Materials Research and Testing, was used to
determine the lateral resolution of the SIL-SNOM-setup. The pattern consists of stripes from 0.5 nm up to 500 nm
generated by metalorganic chemical vapor deposition (MOCVD) on a GaAs substrate. The different layers are
Al0.65Ga0.35As and In0.33Ga0.67As. Figure 3a) shows the scheme of the pattern. The SIL image in figure 3b) is measured in
reflectance mode with a ZrO2 lens. The cross section in figure 3c) shows the location between two 50 nm lines with the
nominal 5 nm line in the middle. The FWHM of the smallest line is 30 nm. The lateral resolution of 40.3 ± 1.7 nm can be
calculated using a Gaussian fit. This corresponds to a resolution 10 times as high as the diffraction limit (~λ/15).

Figure 3. a) Scheme of the stripe pattern BAM L-002 (by courtesy of Federal Institute for Materials Research and
Testing. b) Near-field optical measurement with ZrO2-SIL. c) Cross-section.

It can be shown, that even with a tip diameter of 700 nm and a tip point angle of 130° the lateral resolution is in the range
of about 30 nm. This is higher than commonly achieved solely by the increase of the numerical aperture. The special
design of the SIL combines the advantage of the increase of the numerical aperture due to the higher refractive index but
also due to a dieelectric interaction with the near-field. Furthermore, the light throughput is high (=high signal to noise
ratio) which provides many possibilities for contrast enhancement. This can also be used to illuminate the sample with
polychromatic or monochromatic light realizing near-field imaging as well as near-field spectroscopy. Furthermore, due
to the high collection efficiency, Raman or fluorescence spectroscopy as well as spectral imaging will also be possible.

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In SIL technology an evanescent field is generated by total internal reflection at the apex of the probe where the
transition of light from SIL medium into air takes place. Approaching a specimen to the SIL, the evanescent field will be
attenuated e. g. by a scattering center in case of a scattering sample or by a chromophore in case of an absorbing sample.
Thus the evanescent field does not follow any more the classical diffraction theory and allows highly resolved optical
microscopy with the possibility to measure scattering and absorption, meaning morphology and chemistry, at the same
time.

3. SELECTED APPLICATIONS

3.1 Imaging of Glioblastoma multiforme cells

Glioblastoma multiforme represents the most common malignant brain tumor in adults. The mean survival time after
diagnosis is only a few months.28 The extreme malignancy is caused by inactive tumor suppressor genes PTEN and
TP53.29 A tumor model has been developed based on the U-251 MG cell line from a human explant. The tumor model
simulates different malignancies by controlled expression of the tumor suppressor proteins PTEN and TP53 within the
cell lines derived from the wild type. Cells with at least one active tumor suppressor gene are less malignant and
represent the possible beginning of a tumor development.
The cells are grown on gold slides and subsequently fixated with paraformaldehyde, followed by a drying step. Figure 4
shows a glioblastoma multiforme cell of cell line TP53, measured with a ZrO2-SIL under polychromatic illumination.
Figure 4a) depicts the topographic information acquired with the SIL. Figure 4b) represents the optical near-field image.
The globular surface structures are clearly visible with the SIL-SNOM technology.

Figure 4. Glioblastoma multiforme cell of cell line TP53. a) Topographic information acquired with the SIL.
b) Corresponding optical near-field image.

3.2 Monocyte growing to a differentiated dendritic cell

Monocytes represent a part of the leukocytes in blood. Monocytes develop to dendritic cells to attain a surface as big as
possible. This will be achieved through an arboreal branching of the plasma membrane. The preparation of the samples is
described in detail in.2 Very thin and flat cell branches cannot properly be microscoped with optical far-field microscopy
since the contrast is absent and the dimensions of these structures lay near to the resolution boundary of the microscope.
By means of the SIL-SNOM technique, the fine filopodia are contrast-rich resolved. Figure 5 shows two cells with
different degrees of differentiation. The marked section in the image a) is taken with a higher pixel resolution and in
image b) represented. An intensity profile of the marked section of image b) is shown at the bottom, both a cross-section
and a longitudinal section.

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 Figure 5. Top: a) SIL-SNOM image of two dendritic cells. b) shows a sectional magnification of the marked area in
image a) (50 μm x 50 μm). Bottom: Profile of a filopedium of dendritic cells from top figure a) cross-section and b)
longitudinal section.

The filopodium shows a half width value of 228 nm and contains a periodic structure along the branches. The period-
displacement is 139 nm and the half width value of the individual structures is 48 nm. The SIL-SNOM technique shows
a very good contrast in these native cells and the possibility to detect optical changes in the fine cell branches.

3.3 Near-field imaging and near-field spectrum of an aluminium oxide membrane

A possibility of manufacturing ordered structures is the electrolytic oxidation of aluminum. By means of an anodic
oxidation process, hexagonal capillaries are created producing different diameters and lengths.30 Here pores can be
produced with a length of a few nanometers until up to 300 nm. An example is shown in figure 6. The images show the
same image section, but taken with different imaging technologies. The image a) shows the height signal with the AFM
(tapping mode) in pseudo-color and image b) shows the reflection intensity in R-SNOM mode through the SIL. With
both techniques, the pores of the membrane are well represented. The bridges between the pores in R-SNOM are shown
with brighter resolution. The measured average of half-width values of the bridges is 28 nm with the AFM and 48 nm
with the SNOM. Since it is always dealing with a convolution of an object and the mapping function, the measured
bridge width is widened. The pores are slightly better displayed with the AFM, as the probe tip is smaller and fits
therefore better into the pores. The SIL remains only on the surface, but still provides excellent resolution of the pores.

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The near-field VIS spectrum in Figure 6c) is measured through the SIL. The reference is the internal reflection in the SIL
without any substrate. The aluminium oxide membrane substrate has no absorption bands in the visible spectral range.
The spectrum shows interference bands due to the near-field scattering.

Figure 6: top: Imaging of an aluminum oxide membrane surface, a) with the AFM (height signal) and b) with the SIL-
SNOM in R-SNOM mode (analog signal of an photomultiplier tube). c) Near-field VIS spectrum recorded with the solid
immersion lens from a porous aluminium oxide membrane.

4. CONCLUSIONS
In this paper we could show, that a key element in near-field optical microscopy is the transducer, the translation of near-
field information into far-field information. Despite the development of different probe concepts, near-field microscopy
is still more an art than pure science. The concept of a new scanning probe by Ghislain et al.24 has the potential to
develop into a versatile tool in SNOM. We have integrated this conical tip in a standard microscope spectrophotometer
where the tip acts as a direct optical converter of the evanescent field on the sample surface. This evanescent field is then
converted to a propagating field, which can be measured by the detector. With a successful discrimination of the
evanescent parts from the propagating far-field on the sample surface the lateral resolution of a SIL is no more

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diffraction-limited. This concept may be significantly more efficient and easier to handle than comparable apertureless
SNOM types with scattering probes and oscillating tips which need a high effort to discriminate near-field signal from
the background signal.
The major advantages of this SIL technique and its integration into a microscope are therefore the high transmission and
the improved detection efficiency through magnification of the numerical aperture, whereby spectroscopic analysis by
conventional light sources is possible. Additionally, the lens is very stable in operation and easily combinable with light
microscopes. Due to the immersion effect of the lens, the theoretical resolution can be increased by a factor of n². In
combination with the dielectric probe, the lateral resolution can even be further increased by a factor of n³. Our conical
solid immersion lens as an apertureless near-field probe is able to measure at a lateral resolution better than 30 nm with a
tip radius > 350 nm. Further advantages of the SIL are the high transmission efficiency, the illumination and collection
of light with a single probe and the better S/N ratio in spectroscopy and fluorescence measurements. In combination with
the SPM signal, the height information as well as the optical information can be imaged at the same time. The UMSP
also provides a broad range of possibilities for spectroscopic analysis from UV-VIS-NIR to fluorescence life time
imaging in the nanometer scale. Even traditional Raman spectroscopy may be possible. The SIL-technique is suitable as
near-field solution for materials science as well as for life sciences. We show near-field images of a glioblastoma
multiforme cell, of a monocyte differentiating to a dendritic cell and of an aluminium oxide membrane with the
corresponding near-field spectrum. The spectrum shows interference bands due to the near-field scattering.

ACKNOWLEDGEMENT
We acknowledge the financial support of the Bundesministerium für Bildung und Forschung, the German science
foundation (DFG) and support from the Ministry of Science and Art of the State of Baden Württemberg. We
acknowledge the preparation of the monocyte samples by Dr. Christina Merz-Stöckle at the Hertie Institute Tuebingen.

REFERENCES

[1] Michel, K., [Die Grundzüge des Mikroskops in elementarer Darstellung], Wissenschaftliche Verlags-
gesellschaft, Stuttgart, 3rd edition (1981).
[2] Merz, T., "Charakterisierung und Anwendung eines Raster-Nahfeldmikroskops mit Festkörper-
Immersionslinse", PhD thesis, University of Ulm (2009).
[3] Minsky, M., "Memoir on inventing the confocal scanning microscope", Scanning 10, 128-138 (1988).
[4] Hell, S. W. and Wichmann, J., "Breaking the diffraction resolution limit by stimulated emission: stimulated-
emission-depletion fluorescence microscopy", Optics Letters 19, 780-782 (1994).
[5] Isaacson, M., Betzig, E. Harootunian, A. and Lewis, A., "Scanning optical microscopy at λ/10 resolution using
near-field imaging methods", Annals of the New York Academy of Sciences, 484, 448-456 (1986).
[6] Pool, R., "The children of the STM", Science 247, 634-636 (1990).
[7] Synge, E., "Suggested method for extending microscopic resolution into the ultra-microscopic region",
Philosophy Magazine, 6, 356-362 (1928).
[8] O´Keefe, J. A., "Resolving power of visible light", Journal of the Optical Society of America A, 46, 359 (1956).
[9] Ash, E. A. and Nicholls, G., "Super-resolution aperture scanning microscope", Nature, 237, 510-512 (1972).
[10] Pohl, D., Denk, W. and Lanz, M., "Optical stethoscopy: image recording with resolution lambda/20", Applied
Physics Letters, 44, 651-653 (1984).
[11] Lehner, G., [Elektromagnetische Feldtheorie für Ingenieure und Physiker], Springer Verlag Berlin Heidelberg,
6th edition (2008).
[12] Hecht, B., Sick, B., Wild, u. P., Deckert, V., Zenobi, R. Martin, O. J. F. and Pohl, D. W., "Scanning near-field
optical microscopy with aperture probes: Fundamentals and applications", Journal of Chemical Physics 112,
7761 (2000).
[13] Milster, T. D., Jo, J. S. and Hirota, K., "Roles of propagating and evanescent waves in solid immersion lens
systems", Applied Optics, 38, 5046-5057 (1999).

Proc. of SPIE Vol. 8231 82310A-9

Downloaded from SPIE Digital Library on 14 Feb 2012 to 134.103.24.124. Terms of Use: http://spiedl.org/terms
[14] Courjon, D., Bainier, C. and Spajer, M., "Imaging of submicron index variations by scanning optical tunneling",
Journal of Vacuum Science & Technology B, 10, 2436-2439 (1992).
[15] Birnbaum, D., Kook, S. and Kopelman, R., "Near-field scanning optical spectroscopy – spatially resolved
spectra of microcrystals and nanoaggregates in doped polymers", Journal of Physical Chemistry, 97, 3091-3094
(1993).
[16] Zenobi, R. and Deckert, V., Optische Nahfeldmikroskopie und –spektroskopie als Werkzeug in der chemischen
Analytik, Angewandte Chemie, 112, 1814-1825 (2000).
[17] Novotny, L. and Stranick, S., "Near-field optical microscopy and spectroscopy with pointed probes. Annual
Review of Physical Chemistry", 57, 303-331 (2006).
[18] De Lange, F., Cambi, A., Huijbens, R., de Bakker, B., Garcia-Parajo, M., van Hulst, N. and Figdor, C. G., "Cell
biology beyond the diffraction limit: near-field scanning optical microscopy", Journal of Cell Science, 114,
4153-4160 (2001).
[19] Ferber, J., Fischer, U., Hagedorn, N. and Fuchs, H., "Internal reflection mode scanning near-field optical
microscopy with the tetrahedral tip on metallic samples", Applied Physics A, 69, 581-589 (1999).
[20] Wu, Q., Ghislain, L. and Elings, V., "Imaging with solid immersion lenses, spatial resolution, and applications",
Proceedings of the IEEE, 88, 1491-1498 (2000).
[21] Andor Technology, "Non-invasive instrument for skin cancer screening demonstrated", press release, Belfast
(2011).
[22] Krafft, C., "Molekulare Endospektroskopie: Neue instrumentell-analytische Methoden zur medizinischen
Diagnostik", habilitation thesis, Technical University of Dresden (2007).
[23] Steiner, G., Krafft, C., Beleites, C. Sobottka, S. Schackert, G., Koch, E. and Salzer, R., "Fast and objective
classification of tumor tissue by optical vibrational spectroscopy", Springer Proceedings in Physics, 114, 378-
383 (2007).
[24] Ghislain, L and Elings, V., "Near-field scanning solid immersion microscope", Applied Physics Letters, 72,
2779-2781 (1998).
[25] Merz, T. and Kessler, R. W., " Spectroscopic imaging in the near-field with an apertureless solid immersion
lens microscope," Proc. SPIE 6631, 66310V-1-66310V-10 (2007).
[26] Koehler, A., "Ein neues Beleuchtungsverfahren für mikrophotographische Zwecke", Zeitschrift für
wissenschaftliche Mikroskopie und mikroskopische Technik, 10, 4, 433-440 (1893).
[27] Merz, T. and Kessler, R. W., "Determination of the lateral resolution of a cantilever based solid immersion lens
near-field microscope", proceedings of the 14th EMC, 1, 725-726 (2008).
[28] Pschyrembel, W. and Bach, M., [Pschyrembel Klinisches Woerterbuch 2011], 262nd ed., De Gruyter, Berlin
(2010).
[29] Zheng, H.; Ying, H.; Yan, H.; Kimmelman, A. C.; Hiller, D. J.; Chen, A.-J.; Perry, S. R.; Tonon, G.; Chu, G.
C.; Ding, Z.; Stommel, J. M.; Dunn, K. L.; Wiedemeyer, R.; You, M. J.; Brennan, C.; Wang, Y. A.; Ligon, K.
L.; Wong, W. H.; Chin, L. and DePinho, R. A., "p53 and Pten control neural and glioma stem/progenitor cell
renewal and differentiation", Nature 455, 1129-1133 (2008).
[30] Lee, W., Ji, R., Goesele, U. and Nielsch, K., "Fast fabrication of long-range ordered porous alumina membranes
by hard anodization", Nature Materials, 5, 741-747 (2006).

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