Tip-enhanced Raman spectroscopy

Last updated

Tip-enhanced Raman spectroscopy (TERS) is a variant of surface-enhanced Raman spectroscopy (SERS) [1] that combines scanning probe microscopy with Raman spectroscopy. High spatial resolution chemical imaging is possible via TERS, [2] with routine demonstrations of nanometer spatial resolution under ambient laboratory conditions, [3] or better [4] at ultralow temperatures and high pressure.


The maximum resolution achievable using an optical microscope, including Raman microscopes, is limited by the Abbe limit, which is approximately half the wavelength of the incident light. Furthermore, with SERS spectroscopy the signal obtained is the sum of a relatively large number of molecules. TERS overcomes these limitations as the Raman spectrum obtained originates primarily from the molecules within a few tens of nanometers of the tip.

Although the antennas' electric near-field distributions are commonly understood to determine the spatial resolution, recent experiments showing subnanometer-resolved optical images put this understanding into question. [2] This is because such images enter a regime in which classical electrodynamical descriptions might no longer be applicable and quantum plasmonic [5] and atomistic [6] effects could become relevant.


The earliest reports of tip enhanced Raman spectroscopy typically used a Raman microscope coupled with an atomic force microscope. Tip-enhanced Raman spectroscopy coupled with a scanning tunneling microscope (STM-TERS) has also become a reliable technique, since it utilizes the gap mode plasmon between the metallic probe and the metallic substrate. [7] [8]


Tip-enhanced Raman spectroscopy requires a confocal microscope, and a scanning probe microscope. The optical microscope is used to align the laser focal point with the tip coated with a SERS active metal. The three typical experimental configurations are bottom illumination, side illumination, and top illumination, depending on which direction the incident laser propagates towards the sample, with respect to the substrate. In the case of STM-TERS, only side and top illumination configurations can be applied, since the substrate is required to be conductive, therefore typically being non-transparent. In this case, the incident laser is usually linearly polarized and aligned parallel to the tip, in order to generate confined surface plasmon at the tip apex. The sample is moved rather than the tip so that the laser remains focused on the tip. The sample can be moved systematically to build up a series of tip enhanced Raman spectra from which a Raman map of the surface can be built allowing for surface heterogeneity to be assessed with up to 1.7 nm resolution. [9] [10] Subnanometer resolution has been demonstrated in certain cases allowing for submolecular features to be resolved. [11] [12]

A fiber-in-fiber-out near-field scanning optical microscopy (NSOM) probe design for lens-free TERS measurement. FIFO NSOM Raman.gif
A fiber-in-fiber-out near-field scanning optical microscopy (NSOM) probe design for lens-free TERS measurement.

In 2019, Yan group and Liu group at University of California, Riverside developed a lens-free nanofocusing technique, which concentrates the incident light from a tapered optical fiber to the tip apex of a metallic nanowire and collects the Raman signal through the same optical fiber. Fiber-in-fiber-out NSOM-TERS has been developed. [13] [14]


Several research have used TERS to image single atoms and the internal structure of the molecules. [15] [16] [17] [18] In 2019, the Ara Apkarian group at the Center for Chemistry at the Space-Time Limit, University of California, Irvine imaged vibrational normal modes of single porphyrin molecules using TERS. [19] TERS-based DNA sequencing has also been demonstrated. [20]

Related Research Articles

<span class="mw-page-title-main">Raman spectroscopy</span> Spectroscopic technique

Raman spectroscopy is a spectroscopic technique typically used to determine vibrational modes of molecules, although rotational and other low-frequency modes of systems may also be observed. Raman spectroscopy is commonly used in chemistry to provide a structural fingerprint by which molecules can be identified.

<span class="mw-page-title-main">Optical microscope</span> Microscope that uses visible light

The optical microscope, also referred to as a light microscope, is a type of microscope that commonly uses visible light and a system of lenses to generate magnified images of small objects. Optical microscopes are the oldest design of microscope and were possibly invented in their present compound form in the 17th century. Basic optical microscopes can be very simple, although many complex designs aim to improve resolution and sample contrast.

<span class="mw-page-title-main">Resonance Raman spectroscopy</span> Raman spectroscopy technique

Resonance Raman spectroscopy is a variant of Raman spectroscopy in which the incident photon energy is close in energy to an electronic transition of a compound or material under examination. This similarity in energy (resonance) leads to greatly increased intensity of the Raman scattering of certain vibrational modes, compared to ordinary Raman spectroscopy.

<span class="mw-page-title-main">Single-molecule experiment</span>

A single-molecule experiment is an experiment that investigates the properties of individual molecules. Single-molecule studies may be contrasted with measurements on an ensemble or bulk collection of molecules, where the individual behavior of molecules cannot be distinguished, and only average characteristics can be measured. Since many measurement techniques in biology, chemistry, and physics are not sensitive enough to observe single molecules, single-molecule fluorescence techniques caused a lot of excitement, since these supplied many new details on the measured processes that were not accessible in the past. Indeed, since the 1990s, many techniques for probing individual molecules have been developed.

<span class="mw-page-title-main">Near-field scanning optical microscope</span>

Near-field scanning optical microscopy (NSOM) or scanning near-field optical microscopy (SNOM) is a microscopy technique for nanostructure investigation that breaks the far field resolution limit by exploiting the properties of evanescent waves. In SNOM, the excitation laser light is focused through an aperture with a diameter smaller than the excitation wavelength, resulting in an evanescent field on the far side of the aperture. When the sample is scanned at a small distance below the aperture, the optical resolution of transmitted or reflected light is limited only by the diameter of the aperture. In particular, lateral resolution of 6 nm and vertical resolution of 2–5 nm have been demonstrated.

Nanophotonics or nano-optics is the study of the behavior of light on the nanometer scale, and of the interaction of nanometer-scale objects with light. It is a branch of optics, optical engineering, electrical engineering, and nanotechnology. It often involves dielectric structures such as nanoantennas, or metallic components, which can transport and focus light via surface plasmon polaritons.

Chemical imaging is the analytical capability to create a visual image of components distribution from simultaneous measurement of spectra and spatial, time information. Hyperspectral imaging measures contiguous spectral bands, as opposed to multispectral imaging which measures spaced spectral bands.

<span class="mw-page-title-main">Raman microscope</span> Laser microscope used for Raman spectroscopy

The Raman microscope is a laser-based microscopic device used to perform Raman spectroscopy. The term MOLE is used to refer to the Raman-based microprobe. The technique used is named after C. V. Raman, who discovered the scattering properties in liquids.

<span class="mw-page-title-main">Sarfus</span> Optical quantitative imaging technique

Sarfus is an optical quantitative imaging technique based on the association of:

Super-resolution microscopy is a series of techniques in optical microscopy that allow such images to have resolutions higher than those imposed by the diffraction limit, which is due to the diffraction of light. Super-resolution imaging techniques rely on the near-field or on the far-field. Among techniques that rely on the latter are those that improve the resolution only modestly beyond the diffraction-limit, such as confocal microscopy with closed pinhole or aided by computational methods such as deconvolution or detector-based pixel reassignment, the 4Pi microscope, and structured-illumination microscopy technologies such as SIM and SMI.

Nanoneedles may be conical or tubular needles in the nanometre size range, made from silicon or boron-nitride with a central bore of sufficient size to allow the passage of large molecules, or solid needles useful in Raman spectroscopy, light emitting diodes (LED) and laser diodes.

The technique of vibrational analysis with scanning probe microscopy allows probing vibrational properties of materials at the submicrometer scale, and even of individual molecules. This is accomplished by integrating scanning probe microscopy (SPM) and vibrational spectroscopy. This combination allows for much higher spatial resolution than can be achieved with conventional Raman/FTIR instrumentation. The technique is also nondestructive, requires non-extensive sample preparation, and provides more contrast such as intensity contrast, polarization contrast and wavelength contrast, as well as providing specific chemical information and topography images simultaneously.

<span class="mw-page-title-main">Infrared Nanospectroscopy (AFM-IR)</span> Infrared microscopy technique

AFM-IR or infrared nanospectroscopy is one of a family of techniques that are derived from a combination of two parent instrumental techniques. AFM-IR combines the chemical analysis power of infrared spectroscopy and the high-spatial resolution of scanning probe microscopy (SPM). The term was first used to denote a method that combined a tuneable free electron laser with an atomic force microscope equipped with a sharp probe that measured the local absorption of infrared light by a sample with nanoscale spatial resolution.

The operation of a photon scanning tunneling microscope (PSTM) is analogous to the operation of an electron scanning tunneling microscope, with the primary distinction being that PSTM involves tunneling of photons instead of electrons from the sample surface to the probe tip. A beam of light is focused on a prism at an angle greater than the critical angle of the refractive medium in order to induce total internal reflection within the prism. Although the beam of light is not propagated through the surface of the refractive prism under total internal reflection, an evanescent field of light is still present at the surface.

<span class="mw-page-title-main">Nano-FTIR</span> Infrared microscopy technique

Nano-FTIR is a scanning probe technique that utilizes as a combination of two techniques: Fourier transform infrared spectroscopy (FTIR) and scattering-type scanning near-field optical microscopy (s-SNOM). As s-SNOM, nano-FTIR is based on atomic-force microscopy (AFM), where a sharp tip is illuminated by an external light source and the tip-scattered light is detected as a function of tip position. A typical nano-FTIR setup thus consists of an atomic force microscope, a broadband infrared light source used for tip illumination, and a Michelson interferometer acting as Fourier-transform spectrometer. In nano-FTIR, the sample stage is placed in one of the interferometer arms, which allows for recording both amplitude and phase of the detected light. Scanning the tip allows for performing hyperspectral imaging with nanoscale spatial resolution determined by the tip apex size. The use of broadband infrared sources enables the acquisition of continuous spectra, which is a distinctive feature of nano-FTIR compared to s-SNOM. Nano-FTIR is capable of performing infrared (IR) spectroscopy of materials in ultrasmall quantities and with nanoscale spatial resolution. The detection of a single molecular complex and the sensitivity to a single monolayer has been shown. Recording infrared spectra as a function of position can be used for nanoscale mapping of the sample chemical composition, performing a local ultrafast IR spectroscopy and analyzing the nanoscale intermolecular coupling, among others. A spatial resolution of 10 nm to 20 nm is routinely achieved.

A probe tip is an instrument used in scanning probe microscopes (SPMs) to scan the surface of a sample and make nano-scale images of surfaces and structures. The probe tip is mounted on the end of a cantilever and can be as sharp as a single atom. In microscopy, probe tip geometry and the composition of both the tip and the surface being probed directly affect resolution and imaging quality. Tip size and shape are extremely important in monitoring and detecting interactions between surfaces. SPMs can precisely measure electrostatic forces, magnetic forces, chemical bonding, Van der Waals forces, and capillary forces. SPMs can also reveal the morphology and topography of a surface.

<span class="mw-page-title-main">Center for Chemistry at the Space-Time Limit</span>

Center for Chemistry at the Space-Time Limit or CaSTL Center is a National Science Foundation Center for Chemical Innovation.

<span class="mw-page-title-main">Coherent Raman scattering microscopy</span> Multi-photon microscopy technique

Coherent Raman scattering (CRS) microscopy is a multi-photon microscopy technique based on Raman-active vibrational modes of molecules. The two major techniques in CRS microscopy are stimulated Raman scattering (SRS) and coherent anti-Stokes Raman scattering (CARS). SRS and CARS were theoretically predicted and experimentally realized in the 1960s. In 1982 the first CARS microscope was demonstrated. In 1999, CARS microscopy using a collinear geometry and high numerical aperture objective were developed in Xiaoliang Sunney Xie's lab at Harvard University. This advancement made the technique more compatible with modern laser scanning microscopes. Since then, CRS's popularity in biomedical research started to grow. CRS is mainly used to image lipid, protein, and other bio-molecules in live or fixed cells or tissues without labeling or staining. CRS can also be used to image samples labeled with Raman tags, which can avoid interference from other molecules and normally allows for stronger CRS signals than would normally be obtained for common biomolecules. CRS also finds application in other fields, such as material science and environmental science.

<span class="mw-page-title-main">Vartkess Ara Apkarian</span>

Vartkess Ara Apkarian is a noted physical chemist and a Professor of Chemistry at The University of California, Irvine. He is the Director of Center for Chemistry at the Space-Time Limit, a National Science Foundation Center for Chemical Innovation. He graduated from University of Southern California with B.S. degrees in Chemistry followed by Ph.D. degree in chemistry from Northwestern University. Following a postdoctoral fellowship at Cornell University, he joined the University of California as Chemistry faculty in 1983. He served as the Chair of the Chemistry Department (2004-2007) at UC Irvine.

Raman spectroelectrochemistry (Raman-SEC) is a technique that studies the inelastic scattering or Raman scattering of monochromatic light related to chemical compounds involved in an electrode process. This technique provides information about vibrational energy transitions of molecules, using a monochromatic light source, usually from a laser that belongs to the UV, Vis or NIR region. Raman spectroelectrochemistry provides specific information about structural changes, composition and orientation of the molecules on the electrode surface involved in an electrochemical reaction, being the Raman spectra registered a real fingerprint of the compounds.


  1. Sonntag, Matthew D.; Pozzi, Eric A.; Jiang, Nan; Hersam, Mark C.; Van Duyne, Richard P. (18 September 2014). "Recent Advances in Tip-Enhanced Raman Spectroscopy". The Journal of Physical Chemistry Letters. 5 (18): 3125–3130. doi:10.1021/jz5015746. PMID   26276323.
  2. 1 2 Shi, Xian; Coca-López, Nicolás; Janik, Julia; Hartschuh, Achim (2017-04-12). "Advances in Tip-Enhanced Near-Field Raman Microscopy Using Nanoantennas". Chemical Reviews. 117 (7): 4945–4960. doi:10.1021/acs.chemrev.6b00640. ISSN   0009-2665.
  3. Chen, Chi; Hayazawa, Norihiko; Kawata, Satoshi (2014-02-12). "A 1.7 nm resolution chemical analysis of carbon nanotubes by tip-enhanced Raman imaging in the ambient". Nature Communications. 5 (1): 3312. doi: 10.1038/ncomms4312 . ISSN   2041-1723. PMID   24518208.
  4. Lee, Joonhee; Crampton, Kevin T.; Tallarida, Nicholas; Apkarian, V. Ara (April 2019). "Visualizing vibrational normal modes of a single molecule with atomically confined light". Nature. 568 (7750): 78–82. doi:10.1038/s41586-019-1059-9. ISSN   1476-4687. S2CID   92998248.
  5. Zhu, Wenqi; Esteban, Ruben; Borisov, Andrei G.; Baumberg, Jeremy J.; Nordlander, Peter; Lezec, Henri J.; Aizpurua, Javier; Crozier, Kenneth B. (2016-06-03). "Quantum mechanical effects in plasmonic structures with subnanometre gaps". Nature Communications. 7 (1). doi:10.1038/ncomms11495. ISSN   2041-1723. PMC   4895716 .
  6. Barbry, M.; Koval, P.; Marchesin, F.; Esteban, R.; Borisov, A. G.; Aizpurua, J.; Sánchez-Portal, D. (2015-05-04). "Atomistic Near-Field Nanoplasmonics: Reaching Atomic-Scale Resolution in Nanooptics". Nano Letters. 15 (5): 3410–3419. doi:10.1021/acs.nanolett.5b00759. hdl: 10261/136309 . ISSN   1530-6984.
  7. Anderson, Mark S. (2000). "Locally enhanced Raman spectroscopy with an atomic force microscope (AFM-TERS)". Applied Physics Letters. 76 (21): 3130. Bibcode:2000ApPhL..76.3130A. doi:10.1063/1.126546.
  8. Stöckle, Raoul M.; Suh, Yung Doug; Deckert, Volker; Zenobi, Renato (February 2000). "Nanoscale chemical analysis by tip-enhanced Raman spectroscopy". Chemical Physics Letters. 318 (1–3): 131–136. Bibcode:2000CPL...318..131S. doi:10.1016/S0009-2614(99)01451-7.
  9. Hayazawa, Norihiko; Inouye, Yasushi; Sekkat, Zouheir; Kawata, Satoshi (September 2000). "Metallized tip amplification of near-field Raman scattering". Optics Communications. 183 (1–4): 333–336. Bibcode:2000OptCo.183..333H. doi:10.1016/S0030-4018(00)00894-4.
  10. Chen, Chi; Hayazawa, Norihiko; Kawata, Satoshi (12 February 2014). "A 1.7 nm resolution chemical analysis of carbon nanotubes by tip-enhanced Raman imaging in the ambient". Nature Communications. 5: 3312. Bibcode:2014NatCo...5.3312C. doi: 10.1038/ncomms4312 . PMID   24518208.
  11. Jiang, S.; Zhang, X.; Zhang, Y.; Hu, Ch.; Zhang, R.; Liao, Y.; Smith, Z.; Dong, Zh. (6 June 2017). "Subnanometer-resolved chemical imaging via multivariate analysis of tip-enhanced Raman maps". Light Sci Appl. 6 (11): e17098. doi:10.1038/lsa.2017.98. PMC   6062048 . PMID   30167216.
  12. Smolsky, Joseph; Krasnoslobodtsev, Alexey (8 August 2018). "Nanoscopic imaging of oxidized graphene monolayer using Tip-Enhanced Raman Scattering". Nano Research. 11 (12): 6346–6359. doi:10.1007/s12274-018-2158-x. S2CID   139119548.
  13. Kim, Sanggon; Yu, Ning; Ma, Xuezhi; Zhu, Yangzhi; Liu, Qiushi; Liu, Ming; Yan, Ruoxue (2019). "High external-efficiency nanofocusing for lens-free near-field optical nanoscopy". Nature Photonics. 13 (9): 636–643. doi:10.1038/s41566-019-0456-9. ISSN   1749-4893. S2CID   195093429.
  14. Ober, Holly. "Fiber-optic probe can see molecular bonds". UC Riverside News. Retrieved 2020-01-10.
  15. Hou, J. G.; Yang, J. L.; Luo, Y.; Aizpurua, J.; Y. Liao; Zhang, L.; Chen, L. G.; Zhang, C.; Jiang, S. (June 2013). "Chemical mapping of a single molecule by plasmon-enhanced Raman scattering". Nature. 498 (7452): 82–86. Bibcode:2013Natur.498...82Z. doi:10.1038/nature12151. hdl:10261/102366. ISSN   1476-4687. PMID   23739426. S2CID   205233946.
  16. Lee, Joonhee; Tallarida, Nicholas; Chen, Xing; Liu, Pengchong; Jensen, Lasse; Apkarian, Vartkess Ara (2017-10-12). "Tip-Enhanced Raman Spectromicroscopy of Co(II)-Tetraphenylporphyrin on Au(111): Toward the Chemists' Microscope". ACS Nano. 11 (11): 11466–11474. doi: 10.1021/acsnano.7b06183 . ISSN   1936-0851. PMID   28976729.
  17. Tallarida, Nicholas; Lee, Joonhee; Apkarian, Vartkess Ara (2017-10-09). "Tip-Enhanced Raman Spectromicroscopy on the Angstrom Scale: Bare and CO-Terminated Ag Tips". ACS Nano. 11 (11): 11393–11401. doi: 10.1021/acsnano.7b06022 . ISSN   1936-0851. PMID   28980800.
  18. Lee, Joonhee; Tallarida, Nicholas; Chen, Xing; Jensen, Lasse; Apkarian, V. Ara (June 2018). "Microscopy with a single-molecule scanning electrometer". Science Advances. 4 (6): eaat5472. Bibcode:2018SciA....4.5472L. doi:10.1126/sciadv.aat5472. ISSN   2375-2548. PMC   6025905 . PMID   29963637.
  19. Lee, Joonhee; Crampton, Kevin T.; Tallarida, Nicholas; Apkarian, V. Ara (April 2019). "Visualizing vibrational normal modes of a single molecule with atomically confined light". Nature. 568 (7750): 78–82. Bibcode:2019Natur.568...78L. doi:10.1038/s41586-019-1059-9. ISSN   0028-0836. PMID   30944493. S2CID   92998248.
  20. He, Zhe; Han, Zehua; Kizer, Megan; Linhardt, Robert J.; Wang, Xing; Sinyukov, Alexander M.; Wang, Jizhou; Deckert, Volker; Sokolov, Alexei V. (2019-01-16). "Tip-Enhanced Raman Imaging of Single-Stranded DNA with Single Base Resolution". Journal of the American Chemical Society. 141 (2): 753–757. doi:10.1021/jacs.8b11506. ISSN   0002-7863. PMID   30586988. S2CID   58552541.