Bioengineering - Materials & NanoTechnology

David T. Eddington Supported by NSF, NIH, and the Chicago Biomedical Consortium Rapid Diffusion: microfluidic model of yeast chemotropism

Brett et al, 2012, Lab on a Chip Surface to volume ratio: microfluidic circulating cancer cell diagnostic

Launiere et al, 2012, Analytical Chemistry Laminar flow: electrode calibration device for in vivo cyclic voltammetry

Problem Statement and Motivation • The microscale offers several advantages • Rapid diffusion • Large surface to volume ratios • Laminar flow • Process integration • We leverage these microscale phenomena to achieve new experimental possibilities

Sinkala et al, 2012, Lab on a Chip

Technical Approach • Microfluidic devices are fabricated by soft lithography • Microfluidic channels can be made in several materials • Polydimethyl siloxane (PDMS) • Glass • Ridig Plastics (COC, PMMA, PP, PE)

Key Achievements and Future Goals • Microfluidic models of medicine • Islet transplantation functional assay • Circulating tumor cell diagnostic • Microfluidic models of biology • Microfluidic oxygen control • Regional control of microenvironment in brain slice preparations • Microfluidic yeast reorientation assay • Environmental bacteria isolation • Algae culture in microdevices

Dieter Klatt, Bioengineering Grant Support: Campus Research Board, UIC

Problem Statement and Motivation • Various diseases are associated with imbalances in tissue pore pressure.

• Detection of pressure imbalances in the human body may enable early intervention and treatment of disease such as hydrocephalus and portal hypertension.

• Currently there is no non-invasive technique for the determination of pore pressure within the human body.

• Pore pressure effects the resistance of the surrounding tissue to deformation and thus may correlate with Magnetic Resonance Elastography (MRE)-derived parameters.

Technical Approach

Key Achievements and Future Goals

• Two-layer Ecoflex phantom with hollow center exposed to various pressure values.

• Changes in pore pressure correlate with shear stiffness of surrounding tissue.

• Magnetic Resonance Elastography (MRE) for the determination of the shear stiffness at each pressure value.

• MRE has the potential to serve as a noninvasive tool for the determination of pressure changes within biological tissue.

• Future plans: • Increasing the sensitivity of MRE-derived mechanical parameters to pore pressure changes by using 3D SLIM-MRE. • Testing the diagnostic capabilities of 3D SLIM-MRE in animal models of diseases associated with pressure imbalances, such as hypertension and hydrocephalus.

Hui Lu, Ph.D., Bioengineering, Julio Fernandez (Columbia University), Hongbin Li (U of British Columbia)

Problem Statement and Motivation •

Mechanical signals play key role in physiological processes by controlling protein conformational changes

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Uncover design principles of mechanical protein stability

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Relationship between protein structure and mechanical response; Deterministic design of proteins

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Atomic level of understanding is needed from biological understanding and protein design principles

Key Achievements and Future Goals

Technical Approach •

All-atom computational simulation for protein conformational changes – Steered Molecular Dynamics

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Identified key force-bearing patch that controlled the mechanical stability of proteins.

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Free energy reconstruction from non-equilibrium protein unfolding trajectories

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Discovered a novel pathway switch mechanism for tuning protein mechanical properties.

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Force partition calculation for mechanical load analysis

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Calculated how different solvent affect protein’s mechanical resistance.

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Modeling solvent-protein interactions for different molecules •

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Coarse-grained model with Molecular dynamics and Monte Carlo simulations

Goal: Computationally design protein molecules with specific mechanical properties for bio-signaling and bio-materials.

Investigators: M. Stroscio, ECE and BioE; M. Dutta, ECE

Problem Statement and Motivation • Coupling manmade nanostructures with biological structures to monitor/control biological processes.

• For underlying concepts see M. Stroscio and M. Dutta, Integrated Biological-Semiconductor Devices, Proc. of the IEEE, 93, 1772 (2005) and Biological Nanostructures and Applications of Nanostructures in Biology: Electrical, Mechanical, & Optical Properties, edited by Michael A. Stroscio and Mitra Dutta (Kluwer, New York, 2004). TsaiChin Wu, Guijun Zhao, Hui Lu, Mitra Dutta, and Michael A. Stroscio, Quantum-dot-based Aptamer Beacons for K+ Detection, IEEE Sensors Journal, 13, 1549-1553, 2013; Digital Object Identifier: 10.1109/JSEN.2012.2229387

Technical Approach • Synthesis of nanostructures • Binding biomolecules (proteins, DNA, selective-binding aptamers, antibodies) to manmade nanostructures • Modeling electrical, optical and mechanical properties of nanostructures • Experimental characterization of integrated manmade nanostructure-biological structures • Applications of manmade nanobiostructures in biomedical engineering including nanosensors as physiological state indicators, nanoelectronics, optoelectronics, and molecule detection.

Key Achievements and Future Goals • Numerous manmade nanostructures have been functionalized with biomolecules; recent work focuses on integration of luminescent quantum dots with DNA aptamers • Nanostructure-biomolecule complexes have been used to study a variety of biological structures including cells • Interactions between nanostructures with biomolecules and with biological environments have been modeled for a wide variety of systems • Ultimate goal is controlling biological systems at the nanoscale

Michael A. Stroscio, ECE and BioE, and Mitra Dutta, ECE

Problem Statement and Motivation • Use DNA and RNA Aptamers as well as Molecular Beacons for Chem/Bio Sensors • Biomedical Detectors • Detection of Pollutants and Toxins

Technical Approach • Graphene-based FET Fabrication; DNA or RNA Aptamer Sensing Element • Characterization of I-V Curves for Selective Binding of Analytes to Aptamers

• Extension to Quantum-wire Functionalized Aptamers • Extension to Quantum-wire—Aptamers for Simultaneous Detection of Multiple Analytes

Key Achievements and Future Goals • Potassium, Lead, Mercury, Cocaine, specific DNA molecules and other analytes detected; sensors designed for other biomolecules including IgE • Graphene-based and electrolyte-based nanosensors demonstrated

G. Ali Mansoori, Bioengineering & Chemical Engineering Primary Grant Support: ARO, KU, UMSL, ANL

Problem Statement and Motivation •

Experimental and theoretical studies of organic nanostructures derived from petroleum (Diamondoids, asphaltenes, etc.)..

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Quantum and statistical mechanics of small systems - Development of ab initio models and equations of state of nanosystems. Phase transitions, fragmentations.

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Molecular dynamics simulation of small systems - Studies in nonextensivity and internal pressure anomaly of nanosystems.

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DNA-Dendrimers nano-cluster formation, nanoparticle-protein attachment for drug delivery

Key Achievements and Future Goals

Technical Approach •

Nanoparticles-Protein Attachmrnt

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DNA-Dendrimer Nano-Cluster Electrostatics (CTNS, 2005)

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Nano-Imaging (AFM & STM), Microelectrophoresis

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Nonextensivity and Nonintensivity in Nanosystems - A Molecular Dynamics Sumulation J Comput & Theort Nanoscience (CTNS,2005)

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Ab Initio computations (Applications of Gaussian 98)

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Principles of Nanotechnology (Book) World Scientific Pub. Co (2005)

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Nano-Systems Simulations (Molecular Dynamics)

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Statistical Mechanical Modeling and its Application to Nanosystems Handbook of Theor & Comput Nanoscience and Nanotechnology (2005)

Nano-Thermodynamics and Statistical Mechanics •

Phase-Transition and Fragmentation in Nano-Confined Fluids J Comput & Theort Nanoscience (2005)

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Interatomic Potential Models for Nanostructures" Encycl Nanoscience & Nanotechnology (2004)