Linking the Geosciences to Emerging Bio-Engineering Technologies

This website provides information about Sandia's Laboratory Directed Research and Development (LDRD) project that has investigated cross-cutting technologies between the geological and biological sciences. Abstract Executive Summary 1.0 Introduction 2.0 Interactions of Biomolecules with Clay Minerals 3.0 A Geoscience Approach to Modeling Chemical Transport through Skin 4.0 Crossover Technologies in Geophysics and Biomedical Imaging Contact Us Download the entire PDF report (SAND2002-3690) (1.5 MB)

Abstract

This LDRD project was funded to identify and investigate applications in which geosciences could be applied to the biological sciences. Three areas were investigated in this one-year LDRD: biochemistry, bioengineering, and human health. The biochemistry section includes modeling for protein folding and improved drug delivery substrates. For those molecular simulations, a hybrid energy forcefield was developed to model the conformation of an oligopeptide within the clay interlayer. Results demonstrate that the nonbonded interactions are especially important in understanding the control of the structure and function of proteins as modified by inorganic substrates, and that the protein structure may be denatured by the clay surface. More sophisticated molecular simulations involving waters of solvation for the protein, hydrated clay interlayers, and different charged distributions in the clay substrates are recommended for future research. The bioengineering section focuses on drug delivery and hazardous chemical adsorption through the skin. Percutaneous absorption of chemicals was developed using a probabilistic, multiphase, heterogeneous model of the skin. Penetration routes through the skin included intercellular diffusion through the stratum corneum, diffusion through aqueous-phase sweat ducts, and diffusion through oil-phase hair follicles. Mass fluxes were calculated for varying lengths of time, and sensitivity analyses showed that the aqueous solubility limit, thickness of the stratum corneum, and aqueous molecular diffusion coefficient are important input parameters. Complex flow and transport models used for enhanced oil recovery, geothermal energy production, and subsurface contaminant migration could be used to further model percutaneous absorption. The human health section includes a review of the geophysical imaging methods that have been used for imaging the interior of the human body, electrical impedance tomography, and magnetic induction tomography. Accurate 3D interpretations of surface or near surface voltage/current or electromagnetic field measurements are dependent upon the inversion algorithms used. EIT impedance inversion is computationally less challenging than that the EM induction inversion, but rapid and resource-efficient solutions are being developed for geophysical applications.

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Executive Summary

Is application of geosciences research at Sandia National Laboratories to biological and human health systems beneficial to the lab's biotechnology efforts? This LDRD project was funded to answer that question for three application areas: biochemistry, bioengineering, and human health. The efforts included a comprehensive literature search and evaluation of current models and techniques to identify the state-of-the-art geoscience applications for critical areas of biotechnical research. Geoscience-based models and simulations were applied to determine their efficacy to these challenging problems.

Interactions of Biomolecules with Clay Minerals
Preliminary molecular simulations were completed to examine the intercalation of amino acids and oligopeptides in the interlayer of a clay mineral. The complex nature of biomolecules within the interlayer or on the surface of a clay mineral has significance in our fundamental understanding of such disparate topics as drug delivery systems, gene therapy, protein function, and the origin of life. The nonbonded interactions characteristic of the electrostatics and short range bonding are especially important in understanding the control of the structure and function of proteins as modified by inorganic substrates. We use a hybrid energy forcefield allowing for the simultaneous simulation of both clay and oligopeptide to determine the general behavior of various amino acid side chains within the clay interlayer. No atomic nor cell parameter constraints are imposed, thereby allowing complete constant pressure optimization and molecular dynamics with an NPT ensemble. In general, the molecular mechanics simulations suggest that clay surfaces are effective in creating significant nonbonded interactions between the clay and the oligopeptide. These interactions may be competitive with the nonbonded interactions that exist within the oligopeptide chain, and can lead to perturbation of the peptide structure once intercalated. There is evidence of denaturing of the protein structure by the clay surface in our simulations. The oligopeptide-montmorillonite example indicates the strong influence of the interlayer cations in preventing direct contact of the oligopeptide with the clay surface. The polar and charged side chains of the oligopeptide are most likely to interact with the interlayer cations. More sophisticated molecular simulations involving explicit waters of solvation for the protein, hydrated clay interlayers, and different charged distributions in the clay substrates are recommended for future research.

A Geoscience Approach to Modeling Chemical Transport through Skin
A number of similarities exist between models of percutaneous absorption and models of contaminant transport in geologic media. Both systems involve complex, multiphase, heterogeneous structures with transient diffusion and sorption of chemical species. A transient three-phase model of percutaneous absorption of chemicals has been developed in this study using a geoscience approach that includes a probabilistic multiphase heterogeneous model of the skin. Penetration routes through the skin that were modeled include the following: (1) intercellular diffusion through the stratum corneum, which was comprised of an immobile sorptive protein phase (keratinocytes) and mobile aqueous (water) and oil (lipid) phases; (2) diffusion through aqueous-phase sweat ducts; and (3) diffusion through oil-phase hair follicles. Uncertainty distributions were assigned to model parameters and a probabilistic Monte Carlo analysis was performed to simulate mass fluxes through each of the routes. Results yielded a wide distribution of simulated mass fluxes due to the uncertainty in the input variables. At early times (60 seconds), transport through the sweat ducts provided a significant amount of mass flux into the bloodstream. At longer times (1 hour), diffusion through the stratum corneum became important because of its relatively large surface area. Similarly, diffusion through the hair follicles was more significant than diffusion through the sweat ducts at later times because of the larger porosity of hair follicles. Sensitivity analyses using stepwise linear regression were also performed to identify input parameters that were most important to the simulated mass fluxes at different times. This probabilistic analysis of percutaneous absorption (PAPA) method may prove useful to studies of exposure assessment and transdermal drug delivery.

Crossover Technologies in Geophysics and Biomedical Imaging
A common goal to both the medical and geoscience communities is the development of non-invasive methods for peering into the interior of an object. Improved biomedical imaging tools are critical to the diagnosis of numerous human diseases and organ dysfunctions. In this study, we narrow the expanse of various geophysical imaging methods by examining only those which utilize quasi-static electromagnetic fields and electrical impedance estimates for in situ characterization of biological structures within the human body. The problem of imaging the interior object via some non-invasive method can be broadly lumped into two primary steps: measurement of some physical quantity (such as voltage, current, or the electromagnetic fields) on the surface of the body; and utilization of an algorithm which infers the distribution of some physical property (such as electrical conductivity) within the body based solely on these surface measurements. Two imaging methods used by geophysicists for subsurface imaging have found utility as methods for imaging the interior of the human body: electrical impedance tomography and magnetic induction tomography. The principles of operation for each method are based on the observation that different biological tissues have varying capacities for sustaining a flow of electric current that is influenced by, for example, the density of vascularization in a given region. The variations in vascularization can, in some cases, be readily correlated to differences in tissue type such as lung, muscle, and bone tissues in the thorax. In other cases, the variations in the density of vascularization, and hence electrical conductivity, can be attributed to the presence of tumorous growths within the body.

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1.0 Introduction

Geosciences research at Sandia National Laboratories utilizes state-of-the-art techniques to study the fundamental science underlying complex natural physiochemical processes, often spanning time, composition, and length scales well beyond that of the materials and engineering sciences. Until recently, most of this research has been limited to applications associated with natural processes occurring within the mantle, crust, and near-surface regions of the Earth. Application of geoscience analytical, experimental, and theoretical methods to biological and human health systems would be beneficial to SNL programmatic efforts in these areas. In this effort, we have evaluated several crossover applications of the Geosciences research program at SNL to bioengineering, biochemistry, and human health areas. This work includes literature research and preliminary computer modeling to explore the potential for developing tangible links of science and technology in the biological and earth. One application area involves the chemical reactivity and binding of organic constituents, such as amino acids and oligopeptides (models for proteins), to inorganic substrates such as clay mineral surfaces. These hybrid organic-inorganic materials can be utilized in implants and drug delivery systems. A second application area examines the transport of pharmaceuticals to human individuals through the skin layers (percutaneous absorption). Concerns about the mechanisms of drug or chemical transport are critical in transdermal drug delivery and in hazardous chemical exposure assessments. The final application addressed in this study is directed at improving diagnostic imaging of soft tissue through improved interpretation of three-dimensional impedance tomographic imaging. This application is of significance in the diagnosis of cancerous growths.

At present, the research staff in the geosciences departments at SNL are leaders in the research and development of fluid flow and species transport through porous media, partitioning of chemical and molecular species between phases, sorption and reaction kinetics of chemicals in liquids and on solids, and remote electromagnetic imaging of complex multiphase structures. Geoscience-based evaluation and modeling of biological processes, diseased tissue, medical implants or pharmaceutical products could significantly augment the bioengineering and medical research and development efforts at SNL. Moreover, linking geosciences research in geochemistry, geohydrology, geomechanics, and geophysics with these biotechnical arenas complements the ongoing research in physics and computational chemistry.

This report summarizes the results of work performed in Fiscal Year 2002 to examine the feasibility of utilizing crossover technologies in the geosciences and biotechnologies for three specific biological applications. The report includes three separate sections each independently reviewing the state-of-the-art for the application. The first section reviews the computer simulations of the interactions of organic molecules on the clay mineral surfaces (Cygan), the second section discusses the modeling of three-phase percutaneous absorption processes and the application of hydrologic codes to evaluate the transport of chemicals (Ho), and the third section reviews the use of geophysical imaging methods in biomedical applications (Weiss).

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Contact Us

Topic	Contact
Interactions of Biomolecules with Clay Minerals	Randall T. Cygan Sandia National Laboratories P.O. Box 5800, MS-0750 Albuquerque, NM 87185-0750 (505) 844-7216 rtcygan@sandia.gov
A Geoscience Approach to Modeling Chemical Transport through Skin	Clifford K. Ho Sandia National Laboratories P.O. Box 5800, MS-0735 Albuquerque, NM 87185-0735 (505) 844-2384 ckho@sandia.gov
Crossover Technologies in Geophysics and Biomedical Imaging	Chester J. Weiss Sandia National Laboratories P.O. Box 5800, MS-0750 Albuquerque, NM 87185-0750 (505) 284-6347 cjweiss@sandia.gov

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Page created by: Clifford K. Ho

Page updated: December 10, 2002