Influence of molecular weight of polycation polydimethyldiallylammonium and carbon nanotube content on electric conductivity of layer-by-layer films

For biological and engineering applications, nm-thin films with high electrical conductivity and tunable sheet resistance are desirable. Multilayers of polydimethyldiallylammonium chloride (PDADMA) with two different molecular weights (322 and 44.3 kDa) and oxidized carbon nanotubes (CNTs) were constructed using the layer-by-layer technique. The surface coverage of the CNTs was monitored with a selected visible near infrared absorption peak. Both the film thickness and the surface coverage of the CNTs increased linearly with the number of CNT/PDADMA bilayers deposited (film thickness up to 80 nm). Atomic force microscopy images showed a predominantly surface-parallel orientation of CNTs. Ohmic behavior with constant electrical conductivity of each CNT/PDADMA film and conductivity up to 4 · 103 S/m was found. A change in PDADMA molecular weight by almost a factor of ten has no effect on the film thickness and electrical conductivity, only the film/air roughness is reduced. However, increasing CNT concentration in the deposition dispersion from 0.15 up to 0.25 mg/ml results in an increased thickness of a CNT/PDADMA bilayer (by a factor of three). The increased bilayer thickness is accompanied by a decreased electrical conductivity (by a factor of four). The decreased conductivity is attributed to the increased monomer/CNT ratio

Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions

Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors

Vertical diffusion of polyelectrolytes in polyelectrolyte multilayers during film preparation and post preparation treatment

The layer-by-layer method is a robust way of surface functionalization using a wide range of materials, e.g. synthetic and natural polyelectrolytes (PEs), proteins and nanoparticles. Thus, this method yields films with applications in diverse areas including biology and medicine. Sequential adsorption of different oppositely charged macromolecules can be used to prepare tailored films with controlled molecular organization. In biomedical research, electrically conductive coatings are of interest. In manuscript 1, we investigated films sequentially assembled from the polycation poly (diallyldimethyl-ammonium) (PDADMA) and modified carbon nanotubes (CNTs), with CNTs serving as the electrically conductive material. We assume that charge transport occurs through CNT contacts. We showed that with more than four CNT/PDADMA bilayers, the electrical conductivity is constant and independent of the number of CNT/PDADMA bilayers. A conductivity up to 4∙10^3 S/m was found. It is possible to control the conductivity with the CNT concentration of the CNT deposition suspension. A higher CNT concentration resulted in thicker CNT/PDADMA bilayers, but in a lower conductivity per bilayer. We suspect that an increased CNT concentration leads to a rapid CNT adsorption without the possibility to rearrange themselves. If PDADMA then adsorbs on the disordered CNTs in the next deposition step, the average thickness of the polymer layer is thicker than on the more ordered CNT layer from the dilute solution. This leads to an increased PE monomer/CNT ratio and lower conductivity. More polycations between the CNT layers leads to less CNT contacts. Thus, the controlled composition of films can be used to fulfill specific requirements. For many applications of polyelectrolyte multilayers (PEMs), cheap PEs with a broad distribution of molecular weights are used. It was unknown whether the distribution of molecular weights of the PE in the adsorption solution is maintained during the adsorption process and hence in the film. To investigate this, the PSS adsorption solution in article 2 consisted of a binary mixture of short and long poly (styrene sulfonate) (PSS). A good model system to study layered films in terms of composition are PDADMA/PSS multilayers. Neutron reflectivity and in-situ ellipsometry measurements were carried out to determine the PSS composition in the film and the growth regimes. At a mole fraction of long PSS of 5 % or more in solution, the exponential growth (which is characteristic of short PSS) is totally suppressed, and only long PSS is deposited in the resulting multilayer. Variation of adsorption time of PSS showed that short PSS first adsorbs to the surface but is displaced by long PSS. Between 0 and 5 % of long PSS in the adsorption solution exponential growth occurs. The fraction of short PSS in the film continuously decreases with the increase of long PSS in the adsorption solution. In the assembly of films prepared from binary PSS mixtures, the short PSS leaves the film through adsorption/desorption steps both during PSS adsorption and during PDADMA adsorption (as PDADMA/PSS complexes). Both techniques show that the composition of the film does not correspond to that of the deposition solution. The composition and thus the properties of the resulting multilayer are influenced by the choice of adsorption time. Moreover, we conclude that a multilayer grown from a polydisperse polyelectrolyte contains fewer mobile low molecular weight polymers than the deposition solution. In manuscript 1 and article 2, the composition of multilayers was studied. In manuscript 1 adsorption kinetics were important for the arrangement of CNTs on the surface. In article 2, the adsorption kinetics, i.e. the diffusion of the polyelectrolytes to the surface, was also investigated. In article 3, we investigated the influence of the composition of the film as well as the preparation condition on the mobility of PEs in the film. The molecular weight of the polycation PDADMA and the NaCl concentration of the deposition solution were varied. The vertical PSS diffusion constant D_PSS within the PDADMA/PSS multilayers was measured using neutron reflectivity. The salt concentration of the preparation solution defines the polymer conformation during deposition. The molecular weight of the polycation determines the degree of intertwining. Together, both parameters determine the polyanion-polycation coupling and thus the PSS mobility within the network. Log−log display of D_PSS vs the molecular weight of PDADMA and fits to two power laws (D_PSS ∝ X_n(PDADMA)^(-m) ∝ M_w(PDADMA)^(-m)) reveals for films built from 10 or 200 mM NaCl a kink. Below and above the kink, the dependence of D_PSS on M_w(PDADMA) can be described by different power laws. For Χ_n(PDADMA) X_n,kink(PDADMA) ≈ 288, the decrease of D_PSS with M_w(PDADMA) is larger than below the entanglement limit, which is indicative of sticky reptation and entanglement. The PSS diffusion constant of films built from 100 mM NaCl drops three orders of magnitude when increasing the molecular weight of PDADMA from 45 kDa to 72 kDa. To figure out if an immobile PSS fraction exists in the film built from 72 kDa PDADMA (beyond the entanglement limit), the film was annealed at different conditions in article 4: both temperature and salt concentration were varied. For data analysis, the simplest model with two PSS fractions with different diffusion constants was used. These diffusion constants increase as the temperature of the surrounding solution is increased. As assumed in article 3, an immobile PSS fraction exists when annealing at room temperature. At higher annealing temperatures, at least two diffusion processes must be distinguished: the diffusion of the highly mobile PSS fraction through the entire film and a slow PSS fraction, mowing in a limited way. The choice of preparation conditions determines whether a polyelectrolyte multilayer can intermix completely. It is not clear if complete intermixing will ever occur for films built with PDADMA beyond the entanglement limit. It is possible that the diffusion is more complex. Long-term measurements will clarify this question. Calculating scattering length density profiles with subdiffusive behavior would be interesting and is a challenge for the future. Furthermore, immobile fractions are only visible with long annealing times. We hypothesize that an immobile or nearly immobile fraction is present whenever the dependence of D_PSS on the molecular weight of PDADMA cannot be described by the sticky reptation. To verify this hypothesis, further studies are necessary. All results presented and discussed in the manuscript and articles show that by varying the preparation conditions, tailored films can be built. The composition of the film is also determined by the adsorption kinetics. In addition, the mobility of the PEs within the multilayers can be controlled by varying the conformation, mingling and entanglement of the chains within the film. The influence of the salt concentration in the preparation solution on the growth regimes during film formation is part of our future research. It is planned to investigate films built of different PDADMA molecular weights under varied annealing conditions to better understand the mobile and immobile fractions.Das Layer-by-Layer Verfahren ist eine robuste Methode zur Oberflächenfunktionalisierung unter Verwendung einer breiten Auswahl an Materialien (z. B. synthetische und natürliche Polyelektrolyte (PEs), Proteine und Nanopartikel). Die sequentielle Adsorption verschiedener entgegengesetzt geladener Makromoleküle kann zur Herstellung maßgeschneiderter Filme mit kontrollierter molekularer Organisation verwendet werden. In der biomedizinischen Forschung sind elektrisch leitfähige Beschichtungen von Interesse. In Manuskript 1 untersuchten wir Filme, die abwechselnd aus dem Polykation Poly(diallyldimethylammonium) (PDADMA) und modifizierten Kohlenstoffnanoröhren (CNTs) aufgebaut wurden, wobei die CNTs als elektrisch leitendes Material dienen. Wir haben gezeigt, dass bei mehr als vier CNT/PDADMA-Doppelschichten die elektrische Leitfähigkeit konstant und unabhängig von der Anzahl der CNT/PDADMA-Doppelschichten ist. Es wurde eine Leitfähigkeit von bis zu 4*10^3 S/m gefunden. Es ist möglich, die Leitfähigkeit mit der CNT-Konzentration der CNT-Depositionssuspension zu steuern. Eine höhere CNT-Konzentration führte zu einem erhöhten PE-Monomer/CNT-Verhältnis. Mehr Polykationen zwischen den CNT-Schichten bedeuten weniger CNT-Kontakte, was zu einer geringeren Leitfähigkeit führt. So kann die kontrollierte Zusammensetzung der Filme genutzt werden, um spezifische Anforderungen zu erfüllen. Für viele Anwendungen von Polyelektrolyt-Multischichten (PEMs) werden preiswerte PEs mit einer breiten Verteilung der Molmassen verwendet. Es war nicht klar, ob die Molmassenverteilung des PE in der Adsorptionslösung während des Adsorptionsprozesses und damit im Film erhalten bleibt. Um dies zu untersuchen, bestand die PSS-Adsorptionslösung in Artikel 2 aus einer binären Mischung aus kurzem und langem Poly(styrolsulfonat) (PSS). Es wurden Neutronenreflexions- und In-situ-Ellipsometriemessungen durchgeführt, um die PSS-Zusammensetzung im Film und die Wachstumsregime zu bestimmen. Bei einem Molanteil an langem PSS von 5 % oder mehr in der Lösung wird das exponentielle Wachstum (das für kurzes PSS charakteristisch ist) vollständig unterdrückt, und nur langes PSS wird in der resultierenden Multischicht abgeschieden. Die Variation der Adsorptionszeit von PSS zeigte, dass kurzes PSS zuerst an der Oberfläche adsorbiert, aber von langem PSS verdrängt wird. Der Anteil der kurzen PSS Moleküle im Film nimmt mit der Zunahme der langen PSS Moleküle in der Adsorptionslösung kontinuierlich ab. Beim Aufbau von Filmen, die aus binären PSS-Gemischen hergestellt wurden, verlässt das kurze PSS den Film durch Adsorptions-/Desorptionsprozesse sowohl während der PSS-Adsorption als auch während der PDADMA-Adsorption (als PDADMA/PSS-Komplexe). Beide Techniken zeigen, dass die Zusammensetzung des Films nicht derjenigen der Depositionslösung entspricht. Außerdem kommen wir zu dem Schluss, dass eine aus einem polydispersen Polyelektrolyten präparierte Multischicht weniger mobile niedermolekulare Polymere enthält als die Adsorptionslösung. In Artikel 3 untersuchten wir den Einfluss der Zusammensetzung der Filme sowie der Herstellungsbedingungen auf die Mobilität der PEs innerhalb des Films. Die molare Masse des Polykations PDADMA und die NaCl-Konzentration der Adsorptionslösung wurden variiert. Die vertikale PSS-Diffusionskonstante innerhalb der PDADMA/PSS-Multischichten wurde mit Hilfe der Neutronenreflexion ermittelt. Die Salzkonzentration der Präparationslösung bestimmt die Polymerkonformation während der Abscheidung. Die molare Masse des Polykations bestimmt den Grad der Verschränkung. Beide Parameter zusammen bestimmen die PSS-Mobilität innerhalb des Netzwerks. Die log-log-Darstellung der Diffusionskonstante von PSS gegen die molare Masse von PDADMA und die Anpassung an zwei Potenzgesetze zeigt für Filme aus 10 oder 200 mM NaCl einen Knick. Wir verstehen den Knick als die Verschränkungsgrenze. Unterhalb des Knicks stimmen die Exponenten mit den Vorhersagen des sticky reptation Modells überein. Oberhalb des Knicks nimmt die Diffusionskonstante von PSS schneller ab, als das sticky reptation Modell vorhersagt. Die PSS-Diffusionskonstante von Filmen, die aus 100 mM NaCl hergestellt wurden, fällt um drei Größenordnungen, wenn die molare Masse des PDADMA von 45 kDa auf 72 kDa erhöht wird. Um herauszufinden, ob in dem aus 72 kDa PDADMA (jenseits der Verschränkungsgrenze) hergestellten Film ein immobiler PSS-Anteil vorhanden ist, wurde der Film unter verschiedenen Bedingungen nachbehandelt (siehe Artikel 4): sowohl die Temperatur als auch die Salzkonzentration wurde variiert. Für die Datenanalyse wurde das einfachste Modell mit zwei PSS-Fraktionen mit unterschiedlichen Diffusionskonstanten verwendet. Diese Diffusionskonstanten nehmen zu, wenn die Temperatur der umgebenden Lösung erhöht wird. Wie in Artikel 3 angenommen, gibt es eine immobile PSS-Fraktion, wenn bei Raumtemperatur nachbehandelt wird. Bei höheren Ausheiltemperaturen müssen mindestens zwei Diffusionsprozesse unterschieden werden: die Diffusion der hochmobilen PSS-Fraktion durch den gesamten Film und eine langsame PSS-Fraktion, die nur begrenzt diffundiert. Die Wahl der Präparationsbedingungen bestimmt, ob sich eine Polyelektrolyt-Multischicht vollständig durchmischen kann. Wir stellen die Hypothese auf, dass ein immobiler oder nahezu immobiler Anteil immer dann vorhanden ist, wenn die Abhängigkeit der Diffusionskonstante von PSS von der molaren Masse von PDADMA nicht durch sticky reptation beschrieben werden kann. Um diese Hypothese zu überprüfen, sind weitere Untersuchungen erforderlich. Alle im Manuskript und in den Artikeln vorgestellten und diskutierten Ergebnisse zeigen, dass durch Variation der Präparationsbedingungen maßgeschneiderte Filme hergestellt werden können. Die Zusammensetzung des Films wird auch durch die Adsorptionskinetik bestimmt. Darüber hinaus kann die Mobilität der PEs innerhalb der Multischichten durch Variation der Konformation, Vermischung und Verschränkung der Ketten innerhalb des Films gesteuert werden

Influence of Different Solutions on Electrically Conductive Films Composed of Carbon Nanotubes and Polydimethyldiallylammonium

For engineering and biomedical applications, nanometer-thin films with high electrical conductivity in aqueous solutions are desirable. Multilayers of polydimethyldiallylammonium chloride (PDADMA) and oxidized carbon nanotubes (CNTs) were built using the layer-by-layer technique. CNTs with a low linear charge density were used. The surface coverage of the CNTs was monitored with optical absorption. The film thickness and the surface coverage of the CNTs increased linearly with the number of CNT/PDADMA bilayers deposited. On immersion into aqueous solutions, the film thickness decreased or remained constant. This finding is attributed to the hydrophobic character of the CNTs and the backbone of PDADMA. The films showed ohmic behavior, both in air and in solutions. The electrical conductivity was 0.95 × 104 S/m in air and increased to 1.36 × 104 S/m in solution, provided the thickness of the CNT/PDADMA bilayers was as low as 1.9 nm. We suggest that high electrical conductivity can be achieved by flat adsorption of the CNTs