arXiv subjects

Anthony N. Consiglio

Publications and source records attributed to Anthony N. Consiglio.

5 recordsLinked to original sources

arXiv2026

Time-Resolved Multi-Spectral X-ray Computed Tomography of Cryoprotectant Diffusion Into Biomimetic Material

Cryopreservation via vitrification requires loading cryoprotective cocktails. Insufficient loading may lead to freezing, precluding successful recovery; overloading is toxic. Yet, existing in situ measurements of cryoprotectant permeation remain largely unvalidated and do not resolve individual cryoprotectant concentrations. We introduce multi-spectral X-ray computed tomography (MSCT) to noninvasively quantify the spatiotemporal distribution of cryoprotectants diffusing into a tissue mimicking phantom. A developed photon-energy bin selection algorithm achieves sensitivity to low contrast cryoprotectants without contrast agents or fluorescence edges. The technique is validated with a dimethyl sulfoxide, glycerol, and water solution, resolving cryoprotectant volume fractions to within 5% accuracy. We observe heterogeneous diffusion of the cryoprotectants into the tissue mimicking hydrogel, a phenomenon not observable with conventional techniques. MSCT improves upon existing X ray CT methods because it is not underdetermined for multicomponent solutions and does not implicitly assume homogeneous diffusion. These advancements enable the systematic development of cryoprotectant loading protocols and provide diagnostics to assess vitrifiability before cryopreservation.

physics.med-ph↗

arXiv2026

Thermodynamic principles of emerging cryopreservation technologies

Modern cryopreservation exists at the convergence of diverse disciplines--materials science, physical chemistry, mechanical engineering, biological engineering, etc.--and emerging technologies often draw from many of these disciplines simultaneously. Thermodynamics, as one of the foundational theories underlying both physical and biological science, provides a framework through which to understand these interdisciplinary technologies, yet the full kit of requisite thermodynamic tools is not housed within any one discipline. This Chapter aims to articulate a foundational thermodynamic approach to the description, interrogation, and design of modern cryopreservation technologies, and to review the state of the art in emerging cryopreservation technologies through the lens of this approach. We focus in particular on the management of phase change across equilibrium-driven techniques (e.g., liquidus tracking, partial freezing, isochoric freezing), kinetics-driven techniques (e.g. supercooling, ice seeding), and transport-driven techniques (e.g. directional freezing, droplet approaches), and we hope to equip the reader with a self-consistent theoretical toolkit that enables meaningful comparison of these techniques from a thermodynamic perspective.

physics.chem-ph↗

arXiv2023

Direct Comparison of Isobaric and Isochoric Vitrification of Two Aqueous Solutions with Photon Counting X-Ray Computed Tomography

Vitrification is a promising approach for ice-free cryopreservation of biological material, but progress is hindered by the limited set of experimental tools for studying processes in the interior of the vitrified matter. Isochoric cryopreservation chambers are often metallic, and their opacity prevents direct visual observation. In this study, we introduce photon counting X-ray computed tomography (CT) to compare the effects of rigid isochoric and unconfined isobaric conditions on vitrification and ice formation during cooling of two aqueous solutions: 50 wt% DMSO and a coral vitrification solution, CVS1. Previous studies have only compared vitrification in isochoric systems with isobaric systems that have an exposed air-liquid interface. We use a movable piston to replicate the surface and thermal boundary conditions of the isochoric system yet maintain isobaric conditions. When controlling for the boundary conditions we find that similar ice and vapor volume fractions form during cooling in isochoric and isobaric conditions. Interestingly, we observe distinct ice and vapor cavity morphology in the isochoric systems, possibly due to vapor outgassing or cavitation as rapid cooling causes the pressure to drop in the confined systems. These observations highlight the array of thermo-fluidic processes that occur during vitrification in confined aqueous systems and motivate the further application of imaging techniques such as photon counting X-ray CT in fundamental studies of vitrification.

physics.med-ph↗

arXiv2023

An extreme value statistics model of heterogeneous ice nucleation for quantifying the stability of supercooled aqueous systems

The propensity of water to remain in a metastable liquid state at temperatures below its equilibrium melting point holds significant potential for cryopreserving biological material such as tissues and organs. The benefits conferred are a direct result of progressively reducing metabolic expenditure due to colder temperatures while simultaneously avoiding the irreversible damage caused by the crystallization of ice. Unfortunately, the freezing of water in bulk systems of clinical relevance is dominated by random heterogeneous nucleation initiated by uncharacterized trace impurities, and the marked unpredictability of this behavior has prevented implementation of supercooling outside of controlled laboratory settings and in volumes larger than a few milliliters. Here, we develop a statistical model that jointly captures both the inherent stochastic nature of nucleation using conventional Poisson statistics as well as the random variability of heterogeneous nucleation catalysis through bivariate extreme value statistics. Individually, these two classes of models cannot account for both the time-dependent nature of nucleation and the sample-to-sample variability associated with heterogeneous catalysis, and traditional extreme value models have only considered variation of the characteristic nucleation temperature. We conduct a series of constant cooling rate and isothermal nucleation experiments with physiological saline solutions and leverage the statistical model to evaluate the natural variability of kinetic and thermodynamic nucleation parameters. By quantifying freezing probability as a function of temperature, supercooled duration, and system volume, while accounting for nucleation site variability, this study also provides a basis for the rational design of stable supercooled biopreservation protocols.

cond-mat.mtrl-sci↗

arXiv2022

Methods to stabilize aqueous supercooling identified by use of an isochoric nucleation detection (INDe) device

Stable aqueous supercooling has shown significant potential as a technique for human tissue preservation, food cold storage, conservation biology, and beyond, but its stochastic nature has made its translation outside the laboratory difficult. In this work, we present an isochoric nucleation detection (INDe) platform for automated, high-throughput characterization of aqueous supercooling at >1 mL volumes, which enables statistically-powerful determination of the temperatures and time periods for which supercooling in a given aqueous system will remain stable. We employ the INDe to investigate the effects of thermodynamic, surface, and chemical parameters on aqueous supercooling, and demonstrate that various simple system modifications can significantly enhance supercooling stability, including isochoric (constant-volume) confinement, hydrophobic container walls, and the addition of even mild concentrations of solute. Finally, in order to enable informed design of stable supercooled biopreservation protocols, we apply a statistical model to estimate stable supercooling durations as a function of temperature and solution chemistry, producing first-in-field supercooling stability maps for four common cryoprotective solutes.

cond-mat.mtrl-sci↗