Molecular Relaxation Behavior Research Articles

Abstract B033: Towards magnetic resonance microscopy for liquid biopsy in cancer therapy monitoring

Abstract The advancement of liquid biopsy techniques promises to revolutionize cancer diagnostics and therapy monitoring, by offering a minimally invasive approach to track tumor progression and treatment efficacy. One central issue preventing advancements are innovations in sensor technology, necessary to enable the detection of molecular and cellular biomarkers with sufficient precision. Over the past decade, atomic-scale quantum sensors have emerged as powerful detectors, offering the ability to perform precise measurements of temperature, pressure, and magnetic fields on the single cell scale. These sensors, based on the interaction of spin qubits with their environment, have the unique capability to amplify and exploit environmental interactions for highly accurate detection, making them ideal for complex biological applications. In this context, we present an advanced quantum sensing platform specifically tailored for liquid biopsy applications in cancer therapy monitoring. This platform integrates the capabilities of optical microscopy with magnetic resonance imaging (MRI) techniques, utilizing nitrogen-vacancy (NV) centers in diamond as quantum sensors by converting magnetic resonance signals into optical signals, which are subsequently captured by a high-speed camera. Our platform offers a novel approach, promising quantitative analysis of single cancer cells from liquid samples with unprecedented accuracy. Unlike traditional MRI, our method captures signals over a wide field of view directly in real space. Each camera pixel records a magnetic resonance spectrum, providing detailed multicomponent information about the sample, such as molecular concentration, diffusion, and relaxation behavior, which are critical for understanding the tumor’s microenvironment. Our quantum sensing technology holds significant potential for enhancing the sensitivity of liquid biopsies. By capturing detailed molecular information from blood or other body fluids, it will enable in-depth analysis of Circulating Tumor Cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and other biomarkers. Citation Format: Karl D. Briegel, Robin D. Allert, Dominik B. Bucher, Julia D. Draeger, Nick R v. Grafenstein, Linyan Nie. Towards magnetic resonance microscopy for liquid biopsy in cancer therapy monitoring [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B033.

Understanding water absorption effect on molecular dynamics, microstructures and relaxation behavior of segmented polyurethane elastomers

The influence of water absorption on molecular dynamics, microstructures and relaxation behaviors of polyurethane (PU) elastomers with polyether (poly(tetramethylene glycol), PTMG) soft segments has been studied. Kinetics of water absorption of PU elastomer can be well fitted by Fick's model. However, non-Fickian absorption behavior was observed in the late stage at 60 °C, which was presumed to be related to the plasticization of some hard domains. Broadband dielectric relaxation spectroscopy was used to investigate the molecular dynamics of PU elastomers. The analysis of α-relaxation and Maxwell-Wagner-Sillars interfacial polarization indicated that the water absorption has a great influence on the molecular mobility of soft segment and the interface regions between soft domains and hard domains. Microphase separation structures of PU elastomers consisted of loose, partially regular and compact hard domains. Water molecules could interact with loose hard domains and lead to the plasticization. The results of stress relaxation behavior indicated that water absorption leaded to remarkable increase in the stress relaxation ratio. The deterioration of relaxation properties caused by water absorption was not only related to the soft segments, but also caused by the plasticization of the interface regions and the hard domains.

Correlationship of Drug-Polymer Miscibility, Molecular Relaxation and Phase Behavior of Dipyridamole Amorphous Solid Dispersions.

In present work, a correlationship among quantitative drug-polymer miscibility, molecular relaxation and phase behavior of the dipyridamole (DPD) amorphous solid dispersions (ASDs), prepared with co-povidone (CP), hydroxypropyl methylcellulose phthalate (HPMC P) and hydroxypropyl methylcellulose acetate succinate (HPMC AS) has been investigated. Miscibility predicted using melting point depression approach for DPD with CP, HPMC P and HPMC AS at 25°C was 0.93% w/w, 0.55% w/w and 0.40% w/w, respectively. Stretched relaxation time (τβ) for DPD ASDs, measured using modulated differential scanning calorimetry (MDSC) at common degree of undercooling, was in the order of DPD- CP>DPD-HPMC P>DPD-HPMC AS ASDs. Phase behavior of 12 months aged (25±5°C and 0% RH) spray dried 60% w/w ASDs was tracked using MDSC. Initial ASD samples had homogeneous phase revealed by single glass transition temperature (Tg) in the MDSC. MDSC study of aged ASDs revealed single-phase DPD-CP ASD, amorphous-amorphous and amorphous-crystalline phase separated DPD-HPMC P and DPD-HPMC AS ASDs, respectively. The results were supported by X-ray micro computed tomography and confocal laser scanning microscopy studies. This study demonstrated a profound influence of drug-polymer miscibility on molecular mobility and phase behavior of ASDs. This knowledge can help in designing "physical stable" ASDs.

Effects of chain structure on damping property and local dynamics of phenyl silicone rubber: Insights from experiment and molecular simulation

The dynamic mechanical property of silicone rubbers with different phenyl units and phenyl contents were comprehensively investigated by means of experiments combined with molecular dynamics (MD) simulation. Experimentally, the results indicate that the phenyl units are randomly distributed in the polymer chains and the damping capacity is considerably improved with the augment of phenyl contents. Compared with methylphenyl units, diphenyl units endow the silicone rubber with enhanced mechanical stability, which leads to a wider glass transition region and effective damping temperature range. Furthermore, the MD simulation reveals the equilibrium structures and local dynamics by monitoring the changes of molecular interactions, bond rotation, conformational transition and molecular diffusion during the cooling process, which correlates the dynamic mechanical response to the molecular relaxation behavior. This work provides a deeper insight into the relationship among the composition, microstructure and damping property, which may promote theoretical predictions and scientific basis for the designs of silicone rubber with desired performances.

Nanoparticle Interactions and Molecular Relaxation in PLA/PBAT/Nanoclay Blends

AbstractOrgano-modified clay nanoparticles were mixed at 1 and 5 wt% concentrations with a molten blend of 75 wt% of polylactide (PLA) and 25 wt% poly[(butylene adipate)-co-terephthalate] (PBAT). Three mixing strategies were used to control the localization of nanoclay. Small amplitude oscillatory shear (SAOS) and stress growth tests were conducted to clarify the nanoclay interactions with the blend components and its effect on the molecular relaxation behavior. SAOS and weighted relaxation spectra properties were determined before and after pre-shearing at a rate of 0.01 s−1. Molecular relaxation and its characteristics were influenced by PLA degradation, PBAT droplet coalescence, and nanoclay localization.

Stability of lyophilized albumin formulations: Role of excipient crystallinity and molecular mobility.

In freeze-dried protein formulations, the composition governs the physical forms of the excipients and hence their functionality. It is also necessary to understand the effect of composition on the molecular relaxation behavior, a key factor influencing protein stability. Mannitol (bulking agent) - trehalose (lyoprotectant) - bovine serum albumin (BSA) lyophiles with varying trehalose to BSA mass ratios were investigated. The crystalline phases were characterized by X-ray diffractometry. The secondary structure of albumin in lyophiles and reconstituted solutions was evaluated by IR spectroscopy and circular dichroism, respectively. Dielectric spectroscopy was used to obtain the relaxation time of freeze-dried samples. When trehalose to BSA ratio was 0.2, while mannitol crystallized predominantly as the δ-anhydrous polymorph, trehalose remained amorphous. At lower concentrations of BSA, mannitol crystallized in both hemihydrate and anhydrous forms, and trehalose as dihydrate. The extent of dehydration during subsequent drying was dictated by the trehalose to BSA ratio in the formulation. A gradual increase in the Johari-Goldstein relaxation time was observed as the concentration of trehalose increased in the formulation. BSA was more susceptible to stresses from thawing than drying.

Glass Transition Dynamics and Crystallization Kinetics in the Smectic Liquid Crystal 4-n-Butyloxybenzylidene-4'-n'-octylaniline (BBOA).

The molecular dynamics of 4-n-butyloxybenzylidene-4'-n'-octylaniline (BBOA, abbreviated also as 4O.8) was studied by broadband dielectric spectroscopy (BDS) for samples that were exposed to various thermal treatments. Phase transitions between liquid crystalline phases (N, SmA, SmBhex, and SmBCr) were evidenced by abrupt changes in the temperature dependence of the dielectric permittivity spectra and dielectric relaxation times. A particularly complex dynamic behavior was revealed for the highly ordered SmBCr phase that showed clear evidence for cooperative dynamics of a glass-forming liquid as manifested by a Vogel-Fulcher-Tammann (VFT)-type temperature dependence of its structural relaxation time τ(T). At low temperatures, dependence τ(T) again changes from VFT to Arrhenius behavior, a phenomenon commonly observed for supercooled liquids confined to nanometer length scales and occasionally discussed as strong-fragile transition on heating. In this context, our observation supports the idea of partial orientation disorder in a quenched SmBCr phase, where the length scale of cooperative motions is restricted to the nanometer size of glassy domains causing the deviation from "bulk" VFT-type behavior. Finally, the isothermal crystallization kinetics of the metastable SmBCr phase was studied in detail. On the basis of structural information about the SmBhex and SmBCr phases, determined by X-ray diffraction, the subtle relation between molecular order and relaxation behavior is discussed.

Radiation-induced modification of dielectric relaxation spectra of polyolefins: polyethylenes vs. polypropylene

The molecular relaxation behaviour of polyolefins exposed to high-energy radiation has been investigated by dielectric loss (tan δ) analysis. Therefore, low-density polyethylene, high-density polyethylene (HDPE), and isotactic polypropylene (iPP) were gamma-irradiated in air to various absorbed doses (up to 700 kGy). All relaxation zones (α, β, γ, and δ in the order of decreasing temperature), between 25 K and melting temperature, were studied. The radiation-induced changes observed in the dielectric relaxation spectra were related to the modifications in the structural and morphological parameters attributed to exposure of the polyolefins to radiation. Wide-angle X-ray diffraction, infrared spectroscopy, and gel measurements were used to determine the radiation-induced changes in the crystalline structure, oxidative degradation, and the degree of network formation, respectively. The present study reveals high dielectric and/or relaxation sensitivity of polyolefins to gamma radiation. Disappearance of some relaxations (such as β relaxation in HDPE and low temperature γ and δ relaxations in iPP) is clearly observed with irradiation. For the other relaxations, besides the large changes in the relaxation intensity, radiation also induces smaller/larger changes in the distribution of relaxation times, peak position, and activation energy.

Electro-optic and molecular relaxation behaviour of fluoro substituted achiral unsymmetrical four-ring bent-core mesogen

Electro-optic and molecular relaxation studies in a new achiral unsymmetrical four-ring bent-core mesogen are presented in this study. The compound consists of a laterally fluoro-substituted 3,4′-disubstituted biphenyl unit with an ester linkage between the two phenyl rings as the central unit. The mesomorphic properties were characterised by polarising optical microscopy and differential scanning calorimetry. The compound exhibited enantiotropic B7–Bx phase sequence. The electro-optic studies revealed a bistable switching from planar to a homeotropic state under an electric field in B7 phase. Further memory effect was observed between planar and homeotropic textures after the removal of electric field in B7 phase. Temperature dependent permittivity studies as a function of frequency revealed that the molecular relaxation increases with the increasing temperature in B7 phase than in Bx phase.

Structural Changes and Dielectric Relaxation Behavior of Uniaxially Oriented High Density Polyethylene

The molecular relaxation behavior of an ice-quenched high density polyethylene (HDPE) subjected to solid-state stretching at elevated temperature (100 °C) to various draw ratios (up to Λ=13.7) was examined by means of dielectric spectroscopy. All relaxation zones (α, β and γ, in order of decreasing temperature) between 25 K and melting temperature were studied in the frequency range from 1 kHz to 1 MHz. The changes observed in different dielectric relaxations were related to the orientation-induced modifications of the structural and morphological parameters. In order to investigate orientation-induced structural changes, optical microscopy (OM), scanning electron microscopy (SEM), wide angle X-ray scattering (WAXS), and differential scanning calorimetry (DSC) were employed. Herman's orientation function (fc) was used to quantify the degree of crystal orientation. Complete disappearance of the already weak β relaxation with orientation is attributed to the increase in crystallinity, but the contribution due to a more restricted chain segment mobility in the interlamellar regions of oriented specimens should also be taken into account. Presented results also reveal two different orientation-induced dynamics in the evolution of the dielectric α and γ relaxations connected with the main transformation stages in the drawing of crystalline polymers. The transformation of the initial isotropic into a fully oriented fibrillar structure introduces large changes in the dielectric relaxation spectra of HDPE, especially in the α relaxation zone; by contrast, with further increase in the draw ratio much smaller changes are observed due to the deformation of the fiber structure by longitudinal sliding motions of microfibrils and/or by fibrils slipping past each other.

Nanoscale Phase Analysis of Molecular Cooperativity and Thermal Transitions in Dendritic Nonlinear Optical Glasses

A broad nanoscopic study of a wide-range of dendritic organic nonlinear optical (NLO) self-assembly molecular glasses reveals an intermediate thermal phase regime responsible for both enhanced electric field poling properties and strong phase stabilization after poling. In this paper, the focus is on dendritic NLO molecular glasses involving quadrupolar, liquid crystal, and hydrogen bonding self-assembly mechanisms that, along with chromophore dipole-dipole interactions, dictate phase stability. Specifically, dendritic face-to-face interactions involving arene-perfluoroarene are contrasted to coumarin-containing liquid crystal mesogen and cinnamic ester hydrogen interactions. Both the strength of dendritic interactions and the impact of dipole fields on the relaxation behavior have been analyzed by nanoscale energetic probing and local thermal transition analysis. The presence of dendritic groups was found to fundamentally alter transition temperatures and the molecular relaxation behavior. Thermal transition analysis revealed that molecules with dendritic groups possess an incipient transition (T(1)) preceding the glass transition temperature (T(2)) that provides increased stability and a well-defined electric field poling regime (T(1) < T < T(2)), in contrast to molecular groups lacking dendrons that exhibit only single transitions. On the basis of enthalpic and entropic energetic analyses, thermally active modes below T(1) were found to be intimately connected to the dendron structure. Their corresponding activation energies, which are related to thermal stability, increased moving from cinnamic ester groups to coumarin moieties to arene-perfluoroarene interacting groups. While dendritic NLO materials were found to possess only enthalpic stabilization energies at temperatures relevant for device operation (T < T(1)), the apparent molecular binding energies above T(1) contain a substantial amount (up to ~80%) of cooperative entropic energy. The multiple interactions (from dipole-dipole interactions to local noncovalent dendritic interactions) are discussed and summarized in a model that describes the thermal transitions and phases.

Complete relaxation map of polypropylene: radiation-induced modification as dielectric probe

The molecular relaxation behaviour of isotactic polypropylene (iPP) exposed to gamma radiation in air to various absorbed doses (up to 700 kGy) has been investigated by dielectric loss (\( { \tan }\;\delta \)) analysis; the polar (mainly carbonyl and hydroperoxide) groups that were introduced by radiation-induced oxidation were considered as tracer groups. All relaxation zones (α, β, γ and δ in the order of decreasing temperature), between 25 K and melting temperature, were studied in the frequency range from 1 kHz to 1 MHz. The changes observed in the dielectric relaxation spectra were related to the modifications in the structural and morphological parameters attributed to exposure of the iPP samples to radiation. Wide-angle X-ray diffraction was used to investigate radiation-induced changes in the crystalline structure and degree of crystallinity, since the α relaxation is connected with this phase. Infrared spectroscopy and gel measurements were used to determine the changes in the oxidative degradation and the degree of network formation, respectively. Conclusions derived using different methods were compared. This study reveals high dielectric and/or relaxation sensitivity of iPP to gamma radiation. Disappearance of the low-temperature dielectric (γ and δ) relaxations together with large changes in intensity, position and activation energy of the dielectric α relaxation are observed with gamma irradiation and are mainly connected with oxidative degradation in iPP structure.

A dielectric study of molecular relaxations in irradiated high density polyethylene

The molecular relaxation behaviour of high density polyethylene (HDPE), exposed to gamma radiation in air to various absorbed doses (up to 700 kGy), has been investigated by dielectric loss (tanδ) analysis. All relaxation zones ( γ, β and α, in order of increasing temperature), between 25 K and the melt temperature, were studied in the frequency range from 1 kHz to 1 MHz. The changes observed in the dielectric relaxation spectra were related to the modifications in the structural and morphological parameters attributed to exposure of the samples to radiation. Radiation-induced changes in the crystal fraction, oxidative degradation and degree of network formation, observed by wide angle X-ray scattering (WAXS), differential scanning calorimetry (DSC), infrared spectroscopy (IR) and gel measurements, were well connected with the changes in intensity, position and activation energy of α and γ relaxations. Complete disappearance of the already weak β relaxation with irradiation is attributed to the more restricted chain segment mobility in the net structure, but the contribution due to radiation-induced increase in crystallinity should also be taken into account.

Molecular relaxation behavior of fatty acid‐based vinyl ester resins

AbstractThe experimental characterization of the time‐dependent properties of fatty acid‐based vinyl ester resins with reduced styrene content and emissions was conducted and compared with that of various commercial vinyl ester (VE) resins. Constant heating rate and isothermal, multifrequency sweep experiments were conducted over a wide temperature range using dynamic mechanical analysis. Storage and loss modulus master‐curves were formed using time–temperature superposition (TTSP) and analyzed to quantify the molecular relaxation behavior using accepted techniques and theories. Special attention was focused on determining the effect of reducing styrene weight percent on the derived viscoelastic properties. The fatty acid‐based VE resins were found to have similar or slightly inferior thermomechanical properties and a more pronounced viscoelastic response compared with the commercial resins. However, the research definitively demonstrates that the evaluated fatty acid VE resins are a viable replacement to commercial resins in certain applications with concomitant attractive environmental benefits. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Relaxations and nano-phase-separation in ultraviscous heptanol-alkyl halide mixture

To gain insight into the effects of liquid-liquid phase separation on molecular relaxation behavior we have studied an apparently homogeneous mixture of 5-methyl-2-hexanol and isoamylbromide by dielectric spectroscopy over a broad temperature range. It shows two relaxation regions, widely separated in frequency and temperature, with the low-frequency relaxation due to the alcohol and the high-frequency relaxation due to the halide. In the mixture, the equilibrium dielectric permittivity epsilon(s) of the alcohol is 41% of the pure state at 155.7 K and epsilon(s) of isoamylbromide is approximately 86% of the pure state at 128.7 K. The difference decreases for the alcohol component with decreasing temperature and increases for the isoamylbromide component. The relaxation time tau of 5-methyl-2-hexanol in the mixture at 155.7 K is over five orders of magnitude less than in the pure state, and this difference increases with decreasing temperature, but tau of isoamylbromide in the mixture is marginally higher than in the pure liquid. This shows that the mixture would have two T(g)'s corresponding to its tau of 10(3) s, with values of approximately 121 K for its 5-methyl-2-hexanol component and approximately 108 K for its isoamylbromide component. It is concluded that the mixture phase separates in submicron or nanometer-size aggregates of the alcohol in isoamylbromide, without affecting the latter's relaxation kinetics, while its own epsilon(s) and tau decrease markedly.

Crystallization and molecular relaxation of poly(ethylene terephthalate) annealed in supercritical carbon dioxide

Poly(ethylene terephthalate) was annealed at different temperature and pressure of supercritical carbon dioxide (CO2) using samples quenched from the melt. Crystallization and molecular relaxation behavior due to CO2-annealing of samples were investigated using differential scanning calorimetric and dynamic mechanical measurements. The glass transition and crystallization temperatures significantly decreased with increasing temperature and pressure of CO2. The dynamic mechanical measurement of samples annealed at 150 °C in supercritical CO2 showed three relaxation peaks, corresponding to existence of different amorphous regimes such as rigid, intermediate, and mobile domains. As a result, the mobile chains were likely to facilitate crystallization in supercritical state. It also led to the decreased modulus of CO2-annealed samples with increasing pressure.

Effects of molecular relaxation behavior on sized carbon fiber–vinyl ester matrix composite properties

The mechanical and viscoelastic properties of unidirectional vinyl-ester carbon fiber composites were investigated. A cooperativity analysis of the composites was performed on storage (E′) and loss modulus (E″) master curves obtained from dynamic mechanical analysis. The temperature sensitivity of the horizontal logarithmic shift factors (logaT), cooperativity, obtained from E′ data, was found to vary with the sizing used to pretreat the carbon fibers. The observed variations in the experimental trends in cooperativity with fiber sizing for the composite materials were found to deviate significantly from theory. However, the trends in tensile and apparent shear strength of the composites matched the observed qualitative trends in viscoelastic cooperativity obtained from the storage modulus master curves. These results may suggest that the viscoelastic and ultimate mechanical properties of a composite material are related. However, several inconsistencies were observed when comparing the E″ and E′ data which should also be considered in the interpretation of the experimental results.

Thermal characterization of polyurethane acrylate resins

Polyurethane acrylate resins cured by two different ways, a thermal way and a photochemical way, are investigated by means of differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC). Even if both curing methods lead to the same material from a chemical point of view, we show that important differences exist between the thermocured resin and the photocured resin in terms of molecular relaxation behaviour.

Molecular orientation in novolac cured epoxy resins as studied by rheo-optical FTIR spectroscopy

The molecular orientation and relaxation behavior was studied by rheooptical FTIR spectroscopy during the uniaxial deformation of epoxy resins prepared from the diglycidyl ether of butanediol and novolacs on the basis of bisphenol A. The investigation of orientation phenomena was performed in both the rubbery and the glassy state of the epoxies. Results are discussed with regard to the respective mechanism of deformation. Moreover, the effect of temperature, strain rate, and the molecular weight of the novolacs used on the orientation behavior and the mechanical properties was studied. A significant influence of these parameters on the molecular deformation behavior was observed. The reversibility of the orientation at temperatures above and below the glass transition temperature was examined. Epoxy films were subjected to successive loading–unloading cycles including elongation, relaxation, and annealing. The investigations show that the orientation is completely reversible in the rubbery state, but it is only partly reversible below the glass temperature. © 1998 John Wiley & Sons, Inc. J. Appl. Polym. Sci. 70: 247–259, 1998

Molecular relaxation in the blends of polystyrene/poly(2,6-dimethyl-1,4-phenylene oxide) at low temperature

Molecular relaxation behavior in terms of the α, β, and γ transitions of miscible PS/PPO blends has been studied by means of DMTA and preliminary work has been carried out using DSC. From DSC and DMTA (by tan δ), the observed α relaxation (T α or T g ) of PS, PPO, and the blends, which are intermediate between the constituents, are in good agreement with earlier reports by others. In addition, the β transition (T β ) of PS at 0.03 Hz and 1 Hz is observed at -30 and 20°C, respectively, while the γ relaxation (T γ ) is not observed at either frequency. The T β of PPO is 30°C at 0.03 Hz and is not observed at 1 Hz, while the T γ is -85°C at 0.03 Hz and -70°C at 1 Hz. On the other hand, blend composition-independent β or γ relaxation observed in the blends may be a consequence of the absence ofintra- or intermolecular interaction between the constituents at low temperature. Thus it is suggested that at low temperature, the β relaxation of PS be influenced solely by the local motion of the phenylene ring, and that the β or γ relaxation of PPO be predominated by the local cooperative motions of several monomer units or the rotational motion of the methyl group in PPO.