@misc{BaldKeller2014,
  author    = {Bald, Ilko and Keller, Adrian},
  title     = {Molecular processes studied at a single-molecule level using DNA origami nanostructures and atomic force microscopy},
  series = {Molecules},
  volume    = {19},
  journal   = {Molecules},
  number    = {9},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1420-3049},
  doi       = {10.3390/molecules190913803},
  pages     = {13803 -- 13823},
  year      = {2014},
  abstract  = {DNA origami nanostructures allow for the arrangement of different functionalities such as proteins, specific DNA structures, nanoparticles, and various chemical modifications with unprecedented precision. The arranged functional entities can be visualized by atomic force microscopy (AFM) which enables the study of molecular processes at a single-molecular level. Examples comprise the investigation of chemical reactions, electron-induced bond breaking, enzymatic binding and cleavage events, and conformational transitions in DNA. In this paper, we provide an overview of the advances achieved in the field of single-molecule investigations by applying atomic force microscopy to functionalized DNA origami substrates.},
  language  = {en}
}
@misc{BaldKeller2014,
  author    = {Bald, Ilko and Keller, Adrian},
  title     = {Molecular processes studied at a single-molecule level using DNA origami nanostructures and atomic force microscopy},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {9},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-47584},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-475843},
  pages     = {13803 -- 13823},
  year      = {2014},
  abstract  = {DNA origami nanostructures allow for the arrangement of different functionalities such as proteins, specific DNA structures, nanoparticles, and various chemical modifications with unprecedented precision. The arranged functional entities can be visualized by atomic force microscopy (AFM) which enables the study of molecular processes at a single-molecular level. Examples comprise the investigation of chemical reactions, electron-induced bond breaking, enzymatic binding and cleavage events, and conformational transitions in DNA. In this paper, we provide an overview of the advances achieved in the field of single-molecule investigations by applying atomic force microscopy to functionalized DNA origami substrates.},
  language  = {en}
}
@phdthesis{Prinz2016,
  author    = {Prinz, Julia},
  title     = {DNA origami substrates as a versatile tool for surface-enhanced Raman scattering (SERS)},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-104089},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xviii, 184 Seiten},
  year      = {2016},
  abstract  = {Surface-enhanced Raman scattering (SERS) is a promising tool to obtain rich chemical information about analytes at trace levels. However, in order to perform selective experiments on individual molecules, two fundamental requirements have to be fulfilled. On the one hand, areas with high local field enhancement, so-called "hot spots", have to be created by positioning the supporting metal surfaces in close proximity to each other. In most cases hot spots are formed in the gap between adjacent metal nanoparticles (NPs). On the other hand, the analyte has to be positioned directly in the hot spot in order to profit from the highest signal amplification. The use of DNA origami substrates provides both, the arrangement of AuNPs with nm precision as well as the ability to bind analyte molecules at predefined positions. Consequently, the present cumulative doctoral thesis aims at the development of a novel SERS substrate based on a DNA origami template. To this end, two DNA-functionalized gold nanoparticles (AuNPs) are attached to one DNA origami substrate resulting in the formation of a AuNP dimer and thus in a hot spot within the corresponding gap. The obtained structures are characterized by correlated atomic force microscopy (AFM) and SERS imaging which allows for the combination of structural and chemical information. Initially, the proof-of principle is presented which demonstrates the potential of the novel approach. It is shown that the Raman signal of 15 nm AuNPs coated with dye-modified DNA (dye: carboxytetramethylrhodamine (TAMRA)) is significantly higher for AuNP dimers arranged on a DNA origami platform in comparison to single AuNPs. Furthermore, by attaching single TAMRA molecules in the hot spot between two 5 nm AuNPs and optimizing the size of the AuNPs by electroless gold deposition, SERS experiments at the few-molecule level are presented. The initially used DNA origami-AuNPs design is further optimized in many respects. On the one hand, larger AuNPs up to a diameter of 60 nm are used which are additionally treated with a silver enhancement solution to obtain Au-Ag-core-shell NPs. On the other hand, the arrangement of both AuNPs is altered to improve the position of the dye molecule within the hot spot as well as to decrease the gap size between the two particles. With the optimized design the detection of single dye molecules (TAMRA and cyanine 3 (Cy3)) by means of SERS is demonstrated. Quantitatively, enhancement factors up to 10^10 are estimated which is sufficiently high to detect single dye molecules. In the second part, the influence of graphene as an additional component of the SERS substrate is investigated. Graphene is a two-dimensional material with an outstanding combination of electronical, mechanical and optical properties. Here, it is demonstrated that single layer graphene (SLG) replicates the shape of underlying non-modified DNA origami substrates very well, which enables the monitoring of structural alterations by AFM imaging. In this way, it is shown that graphene encapsulation significantly increases the structural stability of bare DNA origami substrates towards mechanical force and prolonged exposure to deionized water. Furthermore, SLG is used to cover DNA origami substrates which are functionalized with a 40 nm AuNP dimer. In this way, a novel kind of hybrid material is created which exhibits several advantages compared to the analogue non-covered SERS substrates. First, the fluorescence background of dye molecules that are located in between the AuNP surface and SLG is efficiently reduced. Second, the photobleaching rate of the incorporated dye molecules is decreased up to one order of magnitude. Third, due to the increased photostability of the investigated dye molecules, the performance of polarization-dependent series measurements on individual structures is enabled. This in turn reveals extensive information about the dye molecules in the hot spot as well as about the strain induced within the graphene lattice. Although SLG can significantly influence the SERS substrate in the aforementioned ways, all those effects are strongly related to the extent of contact with the underlying AuNP dimer.},
  language  = {en}
}
@article{RackwitzKopyraDabkowskaetal.2016,
  author    = {Rackwitz, Jenny and Kopyra, Janina and Dabkowska, Iwona and Ebel, Kenny and Rankovic, MiloS Lj. and Milosavljevic, Aleksandar R. and Bald, Ilko},
  title     = {Sensitizing DNA Towards Low-Energy Electrons with 2-Fluoroadenine},
  series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition},
  volume    = {55},
  journal   = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1433-7851},
  doi       = {10.1002/anie.201603464},
  pages     = {10248 -- 10252},
  year      = {2016},
  abstract  = {2-Fluoroadenine ((2F)A) is a therapeutic agent, which is suggested for application in cancer radiotherapy. The molecular mechanism of DNA radiation damage can be ascribed to a significant extent to the action of low-energy (<20 eV) electrons (LEEs), which damage DNA by dissociative electron attachment. LEE induced reactions in (2F)A are characterized both isolated in the gas phase and in the condensed phase when it is incorporated into DNA. Information about negative ion resonances and anion-mediated fragmentation reactions is combined with an absolute quantification of DNA strand breaks in (2F)A-containing oligonucleotides upon irradiation with LEEs. The incorporation of (2F)A into DNA results in an enhanced strand breakage. The strand-break cross sections are clearly energy dependent, whereas the strand-break enhancements by (2F)A at 5.5, 10, and 15 eV are very similar. Thus, (2F)A can be considered an effective radiosensitizer operative at a wide range of electron energies.},
  language  = {en}
}
@phdthesis{Heck2017,
  author    = {Heck, Christian},
  title     = {Gold and silver nanolenses self-assembled by DNA origami},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-409002},
  school      = {Universit{\"a}t Potsdam},
  pages     = {ix, 125},
  year      = {2017},
  abstract  = {Nanolenses are linear chains of differently-sized metal nanoparticles, which can theoretically provide extremely high field enhancements. The complex structure renders their synthesis challenging and has hampered closer analyses so far. Here, the technique of DNA origami was used to self-assemble DNA-coated 10 nm, 20 nm, and 60 nm gold or silver nanoparticles into gold or silver nanolenses. Three different geometrical arrangements of gold nanolenses were assembled, and for each of the three, sets of single gold nanolenses were investigated in detail by atomic force microscopy, scanning electron microscopy, dark-field scattering and Raman spectroscopy. The surface-enhanced Raman scattering (SERS) capabilities of the single nanolenses were assessed by labelling the 10 nm gold nanoparticle selectively with dye molecules. The experimental data was complemented by finite-difference time-domain simulations. For those gold nanolenses which showed the strongest field enhancement, SERS signals from the two different internal gaps were compared by selectively placing probe dyes on the 20 nm or 60 nm gold particles. The highest enhancement was found for the gap between the 20 nm and 10 nm nanoparticle, which is indicative of a cascaded field enhancement. The protein streptavidin was labelled with alkyne groups and served as a biological model analyte, bound between the 20 nm and 10 nm particle of silver nanolenses. Thereby, a SERS signal from a single streptavidin could be detected. Background peaks observed in SERS measurements on single silver nanolenses could be attributed to amorphous carbon. It was shown that the amorphous carbon is generated in situ.},
  language  = {en}
}
@article{SchuermannTseringTanzeretal.2017,
  author    = {Sch{\"u}rmann, Robin Mathis and Tsering, Thupten and Tanzer, Katrin and Denifl, Stephan and Kumar, S. V. K. and Bald, Ilko},
  title     = {Resonant Formation of Strand Breaks in Sensitized Oligonucleotides Induced by Low-Energy Electrons (0.5-9 eV)},
  series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition},
  volume    = {56},
  journal   = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1433-7851},
  doi       = {10.1002/anie.201705504},
  pages     = {10952 -- 10955},
  year      = {2017},
  abstract  = {Halogenated nucleobases are used as radiosensitizers in cancer radiation therapy, enhancing the reactivity of DNA to secondary low-energy electrons (LEEs). LEEs induce DNA strand breaks at specific energies (resonances) by dissociative electron attachment (DEA). Although halogenated nucleobases show intense DEA resonances at various electron energies in the gas phase, it is inherently difficult to investigate the influence of halogenated nucleobases on the actual DNA strand breakage over the broad range of electron energies at which DEA can take place (<12 eV). By using DNA origami nanostructures, we determined the energy dependence of the strand break cross-section for oligonucleotides modified with 8-bromoadenine ((8Br)A). These results were evaluated against DEA measurements with isolated (8Br)A in the gas phase. Contrary to expectations, the major contribution to strand breaks is from resonances at around 7 eV while resonances at very low energy (<2 eV) have little influence on strand breaks.},
  language  = {en}
}
@article{HeckPrinzDatheetal.2017,
  author    = {Heck, Christian and Prinz, Julia and Dathe, Andre and Merk, Virginia and Stranik, Ondrej and Fritzsche, Wolfgang and Kneipp, Janina and Bald, Ilko},
  title     = {Gold Nanolenses Self-Assembled by DNA Origami},
  series = {ACS Photonics},
  volume    = {4},
  journal   = {ACS Photonics},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {2330-4022},
  doi       = {10.1021/acsphotonics.6b00946},
  pages     = {1123 -- 1130},
  year      = {2017},
  abstract  = {Nanolenses are self-similar chains of metal nanoparticles, which can theoretically provide extremely high field enhancements. Yet, the complex structure renders their synthesis challenging and has hampered closer analyses so far. Here, DNA origami is used to self-assemble 10, 20, and 60 nm gold nanoparticles as plasmonic gold nanolenses (AuNLs) in solution and in billions of copies. Three different geometrical arrangements are assembled, and for each of the three designs, surface-enhanced Raman scattering (SERS) capabilities of single AuNLs are assessed. For the design which shows the best properties, SERS signals from the two different internal gaps are compared by selectively placing probe dyes. The highest Raman enhancement is found for the gap between the small and medium nanoparticle, which is indicative of a cascaded field enhancement.},
  language  = {en}
}
@phdthesis{Olejko2017,
  author    = {Olejko, Lydia},
  title     = {F{\"o}rster resonance energy transfer (FRET)-based nanophotonics using DNA origami structures},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-396747},
  school      = {Universit{\"a}t Potsdam},
  year      = {2017},
  abstract  = {The field of nanophotonics focuses on the interaction between electromagnetic radiation and matter on the nanometer scale. The elements of nanoscale photonic devices can transfer excitation energy non-radiatively from an excited donor molecule to an acceptor molecule by F{\"o}rster resonance energy transfer (FRET). The efficiency of this energy transfer is highly dependent on the donor-acceptor distance. Hence, in these nanoscale photonic devices it is of high importance to have a good control over the spatial assembly of used fluorophores. Based on molecular self-assembly processes, various nanostructures can be produced. Here, DNA nanotechnology and especially the DNA origami technique are auspicious self-assembling methods. By using DNA origami nanostructures different fluorophores can be introduced with a high local control to create a variety of nanoscale photonic objects. The applications of such nanostructures range from photonic wires and logic gates for molecular computing to artificial light harvesting systems for artificial photosynthesis. In the present cumulative doctoral thesis, different FRET systems on DNA origami structures have been designed and thoroughly analyzed. Firstly, the formation of guanine (G) quadruplex structures from G rich DNA sequences has been studied based on a two-color FRET system (Fluorescein (FAM)/Cyanine3 (Cy3)). Here, the influences of different cations (Na+ and K+), of the DNA origami structure and of the DNA sequence on the G-quadruplex formation have been analyzed. In this study, an ion-selective K+ sensing scheme based on the G-quadruplex formation on DNA origami structures has been developed. Subsequently, the reversibility of the G-quadruplex formation on DNA origami structures has been evaluated. This has been done for the simple two-color FRET system which has then been advanced to a switchable photonic wire by introducing additional fluorophores (FAM/Cy3/Cyanine5 (Cy5)/IRDye®700). In the last part, the emission intensity of the acceptor molecule (Cy5) in a three-color FRET cascade has been tuned by arranging multiple donor (FAM) and transmitter (Cy3) molecules around the central acceptor molecule. In such artificial light harvesting systems, the excitation energy is absorbed by several donor and transmitter molecules followed by an energy transfer to the acceptor leading to a brighter Cy5 emission. Furthermore, the range of possible excitation wavelengths is extended by using several different fluorophores (FAM/Cy3/Cy5). In this part of the thesis, the light harvesting efficiency (antenna effect) and the FRET efficiency of different donor/transmitter/acceptor assemblies have been analyzed and the artificial light harvesting complex has been optimized in this respect.},
  language  = {en}
}
@phdthesis{Choi2018,
  author    = {Choi, Youngeun},
  title     = {DNA origami structures as versatile platforms for nanophotonics},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-421483},
  school      = {Universit{\"a}t Potsdam},
  pages     = {125},
  year      = {2018},
  abstract  = {Nanophotonics is the field of science and engineering aimed at studying the light-matter interactions on the nanoscale. One of the key aspects in studying such optics at the nanoscale is the ability to assemble the material components in a spatially controlled manner. In this work, DNA origami nanostructures were used to self-assemble dye molecules and DNA coated plasmonic nanoparticles. Optical properties of dye nanoarrays, where the dyes were arranged at distances where they can interact by F{\"o}rster resonance energy transfer (FRET), were systematically studied according to the size and arrangement of the dyes using fluorescein (FAM) as the donor and cyanine 3 (Cy 3) as the acceptor. The optimized design, based on steady-state and time-resolved fluorometry, was utilized in developing a ratiometric pH sensor with pH-inert coumarin 343 (C343) as the donor and pH-sensitive FAM as the acceptor. This design was further applied in developing a ratiometric toxin sensor, where the donor C343 is unresponsive and FAM is responsive to thioacetamide (TAA) which is a well-known hepatotoxin. The results indicate that the sensitivity of the ratiometric sensor can be improved by simply arranging the dyes into a well-defined array. The ability to assemble multiple fluorophores without dye-dye aggregation also provides a strategy to amplify the signal measured from a fluorescent reporter, and was utilized here to develop a reporter for sensing oligonucleotides. By incorporating target capturing sequences and multiple fluorophores (ATTO 647N dye molecules), a reporter for microbead-based assay for non-amplified target oligonucleotide sensing was developed. Analysis of the assay using VideoScan, a fluorescence microscope-based technology capable of conducting multiplex analysis, showed the DNA origami nanostructure based reporter to have a lower limit of detection than a single stranded DNA reporter. Lastly, plasmonic nanostructures were assembled on DNA origami nanostructures as substrates to study interesting optical behaviors of molecules in the near-field. Specifically, DNA coated gold nanoparticles, silver nanoparticles, and gold nanorods, were placed on the DNA origami nanostructure aiming to study surface-enhanced fluorescence (SEF) and surface-enhanced Raman scattering (SERS) of molecules placed in the hotspot of coupled plasmonic structures.},
  language  = {en}
}
@phdthesis{Vogel2018,
  author    = {Vogel, Stefanie},
  title     = {Sequence dependency of photon and electron induced DNA strand breaks},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-419669},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xii, 117},
  year      = {2018},
  abstract  = {Deoxyribonucleic acid (DNA) is the carrier of human genetic information and is exposed to environmental influences such as the ultraviolet (UV) fraction of sunlight every day. The photostability of the DNA against UV light is astonishing. Even if the DNA bases have a strong absorption maximum at around 260 nm/4.77 eV, their quantum yield of photoproducts remains very low 1. If the photon energies exceed the ionization energy (IE) of the nucleobases ( ̴ 8-9 eV) 2, the DNA can be severely damaged. Photoexcitation and -ionization reactions occur, which can induce strand breaks in the DNA. The efficiency of the excitation and ionization induced strand breaks in the target DNA sequences are represented by cross sections. If Si as a substrate material is used in the VUV irradiation experiments, secondary electrons with an energy below 3.6 eV are generated from the substrate. This low energy electrons (LEE) are known to induce dissociative electron attachment (DEA) in DNA and with it DNA strand breakage very efficiently. LEEs play an important role in cancer radiation therapy, since they are generated secondarily along the radiation track of ionizing radiation. In the framework of this thesis, different single stranded DNA sequences were irradiated with 8.44 eV vacuum UV (VUV) light and cross sections for single strand breaks (SSB) were determined. Several sequences were also exposed to secondary LEEs, which additionally contributed to the SSBs. First, the cross sections for SSBs depending on the type of nucleobases were determined. Both types of DNA sequences, mono-nucleobase and mixed sequences showed very similar results upon VUV radiation. The additional influence of secondarily generated LEEs resulted in contrast in a clear trend for the SSB cross sections. In this, the polythymine sequence had the highest cross section for SSBs, which can be explained by strong anionic resonances in this energy range. Furthermore, SSB cross sections were determined as a function of sequence length. This resulted in an increase in the strand breaks to the same extent as the increase in the geometrical cross section. The longest DNA sequence (20 nucleotides) investigated in this series, however, showed smaller cross section values for SSBs, which can be explained by conformational changes in the DNA. Moreover, several DNA sequences that included the radiosensitizers 5-Bromouracil (5BrU) and 8-Bromoadenine (8BrA) were investigated and the corresponding SSB cross sections were determined. It was shown that 5BrU reacts very strongly to VUV radiation leading to high strand break yields, which showed in turn a strong sequence-dependency. 8BrA, on the other hand, showed no sensitization to the applied VUV radiation, since almost no increase in strand breakage yield was observed in comparison to non-modified DNA sequences. In order to be able to identify the mechanisms of radiation damage by photons, the IEs of certain DNA sequences were further explored using photoionization tandem mass spectrometry. By varying the DNA sequence, both the IEs depending on the type of nucleobase as well as on the DNA strand length could be identified and correlated to the SSB cross sections. The influence of the IE on the photoinduced reaction in the brominated DNA sequences could be excluded.},
  language  = {en}
}
@article{ChoiKotthoffOlejkoetal.2018,
  author    = {Choi, Youngeun and Kotthoff, Lisa and Olejko, Lydia and Resch-Genger, Ute and Bald, Ilko},
  title     = {DNA origami-based forster resonance energy-transfer Nanoarrays and their application as ratiometric sensors},
  series = {ACS applied materials \& interfaces},
  volume    = {10},
  journal   = {ACS applied materials \& interfaces},
  number    = {27},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {1944-8244},
  doi       = {10.1021/acsami.8b03585},
  pages     = {23295 -- 23302},
  year      = {2018},
  abstract  = {DNA origami nanostructures provide a platform where dye molecules can be arranged with nanoscale accuracy allowing to assemble multiple fluorophores without dye-dye aggregation. Aiming to develop a bright and sensitive ratiometric sensor system, we systematically studied the optical properties of nanoarrays of dyes built on DNA origami platforms using a DNA template that provides a high versatility of label choice at minimum cost. The dyes are arranged at distances, at which they efficiently interact by Forster resonance energy transfer (FRET). To optimize array brightness, the FRET efficiencies between the donor fluorescein (FAM) and the acceptor cyanine 3 were determined for different sizes of the array and for different arrangements of the dye molecules within the array. By utilizing nanoarrays providing optimum FRET efficiency and brightness, we subsequently designed a ratiometric pH nanosensor using coumarin 343 as a pH-inert FRET donor and FAM as a pH responsive acceptor. Our results indicate that the sensitivity of a ratiometric sensor can be improved simply by arranging the dyes into a well-defined array. The dyes used here can be easily replaced by other analyte-responsive dyes, demonstrating the huge potential of DNA nanotechnology for light harvesting, signal enhancement, and sensing schemes in life sciences.},
  language  = {en}
}
@article{HeckKanehiraKneippetal.2018,
  author    = {Heck, Christian and Kanehira, Yuya and Kneipp, Janina and Bald, Ilko},
  title     = {Placement of Single Proteins within the SERS Hot Spots of Self-Assembled Silver Nanolenses},
  series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition},
  volume    = {57},
  journal   = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition},
  number    = {25},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1433-7851},
  doi       = {10.1002/anie.201801748},
  pages     = {7444 -- 7447},
  year      = {2018},
  abstract  = {This study demonstrates the bottom-up synthesis of silver nanolenses. A robust coating protocol enabled the functionalization of differently sized silver nanoparticles with DNA single strands of orthogonal sequence. Coated particles 10nm, 20nm, and 60nm in diameter were self-assembled by DNA origami scaffolds to form silver nanolenses. Single molecules of the protein streptavidin were selectively placed in the gap of highest electric field enhancement. Streptavidin labelled with alkyne groups served as model analyte in surface-enhanced Raman scattering (SERS) experiments. By correlated Raman mapping and atomic force microscopy, SERS signals of the alkyne labels of a single streptavidin molecule, from a single silver nanolens, were detected. The discrete, self-similar aggregates of solid silver nanoparticles are promising for plasmonic applications.},
  language  = {en}
}
@article{KielarXinXuetal.2019,
  author    = {Kielar, Charlotte and Xin, Yang and Xu, Xiaodan and Zhu, Siqi and Gorin, Nelli and Grundmeier, Guido and M{\"o}ser, Christin and Smith, David M. and Keller, Adrian},
  title     = {Effect of staple age on DNA origami nanostructure assembly and stability},
  series = {Molecules},
  volume    = {24},
  journal   = {Molecules},
  number    = {14},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1420-3049},
  doi       = {10.3390/molecules24142577},
  pages     = {12},
  year      = {2019},
  abstract  = {DNA origami nanostructures are widely employed in various areas of fundamental and applied research. Due to the tremendous success of the DNA origami technique in the academic field, considerable efforts currently aim at the translation of this technology from a laboratory setting to real-world applications, such as nanoelectronics, drug delivery, and biosensing. While many of these real-world applications rely on an intact DNA origami shape, they often also subject the DNA origami nanostructures to rather harsh and potentially damaging environmental and processing conditions. Furthermore, in the context of DNA origami mass production, the long-term storage of DNA origami nanostructures or their pre-assembled components also becomes an issue of high relevance, especially regarding the possible negative effects on DNA origami structural integrity. Thus, we investigated the effect of staple age on the self-assembly and stability of DNA origami nanostructures using atomic force microscopy. Different harsh processing conditions were simulated by applying different sample preparation protocols. Our results show that staple solutions may be stored at -20 degrees C for several years without impeding DNA origami self-assembly. Depending on DNA origami shape and superstructure, however, staple age may have negative effects on DNA origami stability under harsh treatment conditions. Mass spectrometry analysis of the aged staple mixtures revealed no signs of staple fragmentation. We, therefore, attribute the increased DNA origami sensitivity toward environmental conditions to an accumulation of damaged nucleobases, which undergo weaker base-pairing interactions and thus lead to reduced duplex stability.},
  language  = {en}
}
@article{VogelEbelSchuermannetal.2019,
  author    = {Vogel, Stefanie and Ebel, Kenny and Sch{\"u}rmann, Robin Mathis and Heck, Christian and Meiling, Till and Milosavljevic, Aleksandar R. and Giuliani, Alexandre and Bald, Ilko},
  title     = {Vacuum-UV and Low-Energy Electron-Induced DNA Strand Breaks},
  series = {ChemPhysChem : a European journal of chemical physics and physical chemistry},
  volume    = {20},
  journal   = {ChemPhysChem : a European journal of chemical physics and physical chemistry},
  number    = {6},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1439-4235},
  doi       = {10.1002/cphc.201801152},
  pages     = {823 -- 830},
  year      = {2019},
  abstract  = {DNA is effectively damaged by radiation, which can on the one hand lead to cancer and is on the other hand directly exploited in the treatment of tumor tissue. DNA strand breaks are already induced by photons having an energy below the ionization energy of DNA. At high photon energies, most of the DNA strand breaks are induced by low-energy secondary electrons. In the present study we quantified photon and electron induced DNA strand breaks in four different 12mer oligonucleotides. They are irradiated directly with 8.44 eV vacuum ultraviolet (VUV) photons and 8.8 eV low energy electrons (LEE). By using Si instead of VUV transparent CaF2 as a substrate the VUV exposure leads to an additional release of LEEs, which have a maximum energy of 3.6 eV and can significantly enhance strand break cross sections. Atomic force microscopy is used to visualize strand breaks on DNA origami platforms and to determine absolute values for the strand break cross sections. Upon irradiation with 8.44 eV photons all the investigated sequences show very similar strand break cross sections in the range of 1.7-2.3x10(-16) cm(2). The strand break cross sections for LEE irradiation at 8.8 eV are one to two orders of magnitude larger than the ones for VUV photons, and a slight sequence dependence is observed. The sequence dependence is even more pronounced for LEEs with energies <3.6 eV. The present results help to assess DNA damage by photons and electrons close to the ionization threshold.},
  language  = {en}
}
@article{HeckKanehiraKneippetal.2019,
  author    = {Heck, Christian and Kanehira, Yuya and Kneipp, Janina and Bald, Ilko},
  title     = {Amorphous Carbon Generation as a Photocatalytic Reaction on DNA-Assembled Gold and Silver Nanostructures},
  series = {Molecules},
  volume    = {24},
  journal   = {Molecules},
  number    = {12},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1420-3049},
  doi       = {10.3390/molecules24122324},
  pages     = {10},
  year      = {2019},
  abstract  = {Background signals from in situ-formed amorphous carbon, despite not being fully understood, are known to be a common issue in few-molecule surface-enhanced Raman scattering (SERS). Here, discrete gold and silver nanoparticle aggregates assembled by DNA origami were used to study the conditions for the formation of amorphous carbon during SERS measurements. Gold and silver dimers were exposed to laser light of varied power densities and wavelengths. Amorphous carbon prevalently formed on silver aggregates and at high power densities. Time-resolved measurements enabled us to follow the formation of amorphous carbon. Silver nanolenses consisting of three differently-sized silver nanoparticles were used to follow the generation of amorphous carbon at the single-nanostructure level. This allowed observation of the many sharp peaks that constitute the broad amorphous carbon signal found in ensemble measurements. In conclusion, we highlight strategies to prevent amorphous carbon formation, especially for DNA-assembled SERS substrates.},
  language  = {en}
}
@misc{HeckKanehiraKneippetal.2019,
  author    = {Heck, Christian and Kanehira, Yuya and Kneipp, Janina and Bald, Ilko},
  title     = {Amorphous Carbon Generation as a Photocatalytic Reaction on DNA-Assembled Gold and Silver Nanostructures},
  series = {Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Mathematisch-Naturwissenschaftliche Reihe},
  number    = {732},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-43081},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-430812},
  pages     = {10},
  year      = {2019},
  abstract  = {Background signals from in situ-formed amorphous carbon, despite not being fully understood, are known to be a common issue in few-molecule surface-enhanced Raman scattering (SERS). Here, discrete gold and silver nanoparticle aggregates assembled by DNA origami were used to study the conditions for the formation of amorphous carbon during SERS measurements. Gold and silver dimers were exposed to laser light of varied power densities and wavelengths. Amorphous carbon prevalently formed on silver aggregates and at high power densities. Time-resolved measurements enabled us to follow the formation of amorphous carbon. Silver nanolenses consisting of three differently-sized silver nanoparticles were used to follow the generation of amorphous carbon at the single-nanostructure level. This allowed observation of the many sharp peaks that constitute the broad amorphous carbon signal found in ensemble measurements. In conclusion, we highlight strategies to prevent amorphous carbon formation, especially for DNA-assembled SERS substrates.},
  language  = {en}
}
@article{EbelBald2020,
  author    = {Ebel, Kenny and Bald, Ilko},
  title     = {Length and Energy Dependence of Low-Energy Electron-Induced Strand Breaks in Poly(A) DNA},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {1},
  publisher = {Molecular Diversity Preservation International},
  address   = {Basel},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21010111},
  pages     = {11},
  year      = {2020},
  abstract  = {The DNA in living cells can be effectively damaged by high-energy radiation, which can lead to cell death. Through the ionization of water molecules, highly reactive secondary species such as low-energy electrons (LEEs) with the most probable energy around 10 eV are generated, which are able to induce DNA strand breaks via dissociative electron attachment. Absolute DNA strand break cross sections of specific DNA sequences can be efficiently determined using DNA origami nanostructures as platforms exposing the target sequences towards LEEs. In this paper, we systematically study the effect of the oligonucleotide length on the strand break cross section at various irradiation energies. The present work focuses on poly-adenine sequences (d(A₄), d(A₈), d(A₁₂), d(A₁₆), and d(A₂₀)) irradiated with 5.0, 7.0, 8.4, and 10 eV electrons. Independent of the DNA length, the strand break cross section shows a maximum around 7.0 eV electron energy for all investigated oligonucleotides confirming that strand breakage occurs through the initial formation of negative ion resonances. When going from d(A₄) to d(A₁₆), the strand break cross section increases with oligonucleotide length, but only at 7.0 and 8.4 eV, i.e., close to the maximum of the negative ion resonance, the increase in the strand break cross section with the length is similar to the increase of an estimated geometrical cross section. For d(A₂₀), a markedly lower DNA strand break cross section is observed for all electron energies, which is tentatively ascribed to a conformational change of the dA₂₀ sequence. The results indicate that, although there is a general length dependence of strand break cross sections, individual nucleotides do not contribute independently of the absolute strand break cross section of the whole DNA strand. The absolute quantification of sequence specific strand breaks will help develop a more accurate molecular level understanding of radiation induced DNA damage, which can then be used for optimized risk estimates in cancer radiation therapy.},
  language  = {en}
}
@misc{EbelBald2020,
  author    = {Ebel, Kenny and Bald, Ilko},
  title     = {Length and Energy Dependence of Low-Energy Electron-Induced Strand Breaks in Poly(A) DNA},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {814},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-44412},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-444125},
  pages     = {13},
  year      = {2020},
  abstract  = {The DNA in living cells can be effectively damaged by high-energy radiation, which can lead to cell death. Through the ionization of water molecules, highly reactive secondary species such as low-energy electrons (LEEs) with the most probable energy around 10 eV are generated, which are able to induce DNA strand breaks via dissociative electron attachment. Absolute DNA strand break cross sections of specific DNA sequences can be efficiently determined using DNA origami nanostructures as platforms exposing the target sequences towards LEEs. In this paper, we systematically study the effect of the oligonucleotide length on the strand break cross section at various irradiation energies. The present work focuses on poly-adenine sequences (d(A₄), d(A₈), d(A₁₂), d(A₁₆), and d(A₂₀)) irradiated with 5.0, 7.0, 8.4, and 10 eV electrons. Independent of the DNA length, the strand break cross section shows a maximum around 7.0 eV electron energy for all investigated oligonucleotides confirming that strand breakage occurs through the initial formation of negative ion resonances. When going from d(A₄) to d(A₁₆), the strand break cross section increases with oligonucleotide length, but only at 7.0 and 8.4 eV, i.e., close to the maximum of the negative ion resonance, the increase in the strand break cross section with the length is similar to the increase of an estimated geometrical cross section. For d(A₂₀), a markedly lower DNA strand break cross section is observed for all electron energies, which is tentatively ascribed to a conformational change of the dA₂₀ sequence. The results indicate that, although there is a general length dependence of strand break cross sections, individual nucleotides do not contribute independently of the absolute strand break cross section of the whole DNA strand. The absolute quantification of sequence specific strand breaks will help develop a more accurate molecular level understanding of radiation induced DNA damage, which can then be used for optimized risk estimates in cancer radiation therapy.},
  language  = {en}
}
@phdthesis{Ebel2021,
  author    = {Ebel, Kenny},
  title     = {Quantification of low-energy electron induced single and double strand breaks in well-defined DNA sequences using DNA origami nanostructures},
  doi       = {10.25932/publishup-50449},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-504499},
  school      = {Universit{\"a}t Potsdam},
  pages     = {111},
  year      = {2021},
  abstract  = {Ionizing radiation is used in cancer radiation therapy to effectively damage the DNA of tumors leading to cell death and reduction of the tumor tissue. The main damage is due to generation of highly reactive secondary species such as low-energy electrons (LEE) with the most probable energy around 10 eV through ionization of water molecules in the cells. A simulation of the dose distribution in the patient is required to optimize the irradiation modality in cancer radiation therapy, which must be based on the fundamental physical processes of high-energy radiation with the tissue. In the present work the accurate quantification of DNA radiation damage in the form of absolute cross sections for LEE-induced DNA strand breaks (SBs) between 5 and 20 eV is done by using the DNA origami technique. This method is based on the analysis of well-defined DNA target sequences attached to DNA origami triangles with atomic force microscopy (AFM) on the single molecule level. The present work focuses on poly-adenine sequences (5'-d(A4), 5'-d(A8), 5'-d(A12), 5'-d(A16), and 5'- d(A20)) irradiated with 5.0, 7.0, 8.4, and 10 eV electrons. Independent of the DNA length, the strand break cross section shows a maximum around 7.0 eV electron energy for all investigated oligonucleotides confirming that strand breakage occurs through the initial formation of negative ion resonances. Additionally, DNA double strand breaks from a DNA hairpin 5'-d(CAC)4T(Bt-dT)T2(GTG)4 are examined for the first time and are compared with those of DNA single strands 5'-d(CAC)4 and 5'- d(GTG)4. The irradiation is made in the most likely energy range of 5 to 20 eV with an anionic resonance maximum around 10 eV independently of the DNA sequence. There is a clear difference between σSSB and σDSB of DNA single and double strands, where the strand break for ssDNA are always higher in all electron energies compared to dsDNA by the factor 3. A further part of this work deals with the characterization and analysis of new types of radiosensitizers used in chemoradiotherapy, which selectively increases the DNA damage upon radiation. Fluorinated DNA sequences with 2'-fluoro-2'-deoxycytidine (dFC) show an increased sensitivity at 7 and 10 eV compared to the unmodified DNA sequences by an enhancement factor between 2.1 and 2.5. In addition, light-induced oxidative damage of 5'-d(GTG)4 and 5'-d((CAC)4T(Bt-dT)T2(GTG)4) modified DNA origami triangles by singlet oxygen 1O2 generated from three photoexcited DNA groove binders [ANT994], [ANT1083] and [Cr(ddpd)2][BF4]3 illuminated in different experiments with UV-Vis light at 430, 435 and 530 nm wavelength is demonstrated. The singlet oxygen induced generation of DNA damage could be detected in both aqueous and dry environments for [ANT1083] and [Cr(ddpd)2][BF4]3.},
  language  = {en}
}
@article{KogikoskiJuniorTapioEdlervonZanderetal.2021,
  author    = {Kogikoski Junior, Sergio and Tapio, Kosti and Edler von Zander, Robert and Saalfrank, Peter and Bald, Ilko},
  title     = {Raman enhancement of nanoparticle dimers self-assembled using DNA origami nanotriangles},
  series = {Molecules : a journal of synthetic chemistry and natural product chemistry / Molecular Diversity Preservation International},
  volume    = {26},
  journal   = {Molecules : a journal of synthetic chemistry and natural product chemistry / Molecular Diversity Preservation International},
  number    = {6},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1420-3049},
  doi       = {10.3390/molecules26061684},
  pages     = {18},
  year      = {2021},
  abstract  = {Surface-enhanced Raman scattering is a powerful approach to detect molecules at very low concentrations, even up to the single-molecule level. One important aspect of the materials used in such a technique is how much the signal is intensified, quantified by the enhancement factor (EF). Herein we obtained the EFs for gold nanoparticle dimers of 60 and 80 nm diameter, respectively, self-assembled using DNA origami nanotriangles. Cy5 and TAMRA were used as surface-enhanced Raman scattering (SERS) probes, which enable the observation of individual nanoparticles and dimers. EF distributions are determined at four distinct wavelengths based on the measurements of around 1000 individual dimer structures. The obtained results show that the EFs for the dimeric assemblies follow a log-normal distribution and are in the range of 10(6) at 633 nm and that the contribution of the molecular resonance effect to the EF is around 2, also showing that the plasmonic resonance is the main source of the observed signal. To support our studies, FDTD simulations of the nanoparticle's electromagnetic field enhancement has been carried out, as well as calculations of the resonance Raman spectra of the dyes using DFT. We observe a very close agreement between the experimental EF distribution and the simulated values.},
  language  = {en}
}