Applications of Nanotechnology in Medical Device Design James Marti, Ph.D. Minnesota Nano Center

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1 Applications of Nanotechnology in Medical Device Design James Marti, Ph.D. Minnesota Nano Center November 4, 2015

2 The University of Minnesota Nano Center An open-use nanotechnology lab with tools for fabricating and testing small scale electronic devices making and analyzing new nanomaterials exploring new applications of nanotech in the life sciences

3 The Minnesota Nano Center Recent Nano Center projects Microelectronic circuits Photonic devices Biosensors Cell growth templates Nanoparticles MEMS Microfluidic cells Quantum dots

4 The Nano Center s Mission Support nanoscale fabrication, synthesis, characterization, and hands-on training in an open environment, available to all qualified users (not just internal UM) Involve industrial users, propagate state-ofthe-art nanoscience techniques to larger economy New nanotech-based products

5 What is Nanotechnology? Nanotechnology: making useful materials and devices at the nanoscale Nanoscale: An object of size (or having a key dimension of size) at or below 100 nanometers.

6 Why Nanotechnology? The ability to do precision engineering at the nanoscale should yield advances in new materials and devices Nanoscale technology is a general purpose or platform technology: can affect all other areas of science and engineering

7 Biomedical Applications of Nanotechnology Nanostructured materials for medical imaging drug delivery thermal therapy Medical devices Passive (sensors) Active (neuromodulation, pacing) Wearable or Implantable

8 Nanomaterials for Imaging and Therapies Objectives: improve imaging contrast (MRI, fluorescence, visual) Deliver drugs or heat to site of action without denaturing or exposing healthy tissue These can be combined as theragnostic materials Images: news.sciencemag. org

9 Nanomaterials for Imaging and Drug Delivery Challenges: Make a stable nanocapsule while maintaining efficacy of the active Get the capsule to its target cell (surface ligands) Achieve desired controlled release

10 Nanocapsules Core-shell vs matrix capsules Active Image: agrolytix.com

11 Nanocapsules For a hydrophobic active Hydrophilic Shell Active Solid lipid Image: agrolytix.com

12 Micelles and Vesicles Micelles: hydrophobic core material Modified lipid molecules with hydrophobic tails, hydrophilic head groups Like surfactants Able to hold hydrophobic drug payloads Image: ecoboss.com.au

13 Micelles and Vesicles Vesicles (ex. liposomes) Lipid molecules line up tail-to-tail, form stable bilayer Folding this into a sphere makes a liposome Now core is hydrophilic Images: montessori-allgaeu.de

14 Surface Modification Additional surface groups are needed to get particle to the desired target Image: rsta.royalsocietypublishing.org

15 Dendrimers Highly branched, three dimensional macromolecules All bonds emanate from a central core Can deliver drug and/or imaging agent

16 Recent Work at the Nano Center Nanostructured materials Nanoparticles for thermal therapy Polymers for nanocapsules Nanostructured films Quantum dots Biomedical devices Sensors Microfluidics Micro power sources Complete List at nano.umn.edu

17 Nanoparticles for Thermal Therapies John Bischof et al, Department of Mechanical Engineering Iron oxide nanoparticles have great potential as diagnostic and therapeutic agents in cancer and other diseases However, biological aggregation severely limits their function Bischof group has successfully encased NPs in a shell of functionalized mesoporous silica that can maintain colloidal stability minimize non-specific cellular uptake

18 Block Co-Polymers Hillmyer et al, Department of Chemistry Nanostructures generated by ordered block co-polymers Producing a variety of co-polymers with different functionalities These can be the bi-functional molecules that make micelles and vesicles

19 Block Co-Polymers for Drug Delivery Hillmyer et al, Department of Chemistry Co-polymers self-assemble into polymeric vesicles which can hold drugs, proteins, cells Applications in targeted drug delivery via films, particles Biodegradable polymers can be used

20 Targeted delivery of gene-based therapeutics/vaccines Chun Wang, Z. Dai, Department of Biomedical Engineering Biodegradable polymers assemble into nanoparticles Multifunctional nanoparticles enhance the efficiency of gene delivery to specific cells

21 Block Co-Polymers Hillmyer et al, University of Minnesota Nanoporous structures generated by ordered block copolymers Minor polymer constituent is etchable, the other etch resistant Original applications in adhesives, elastomers Now targeted to nanostructure templates for drug delivery systems

22 Nanoporous Membrane for Implantable Drug Delivery E.E.Nuxoll, M.A.Hillmyer, & R.A.Siegel, Depts of Pharmacy, Chemistry, Biomedical Engineering Nanoporous block-copolymer film with a microfabricated silicon support protects implanted medical devices from fouling immunoproteins permits fast transport of small molecules into and out of the device Confocal microscopy image showing the 100 nm thick polymer film spanning an array of 20um wide pores on a microfabricated silicon support.

23 Silicon Quantum Dots U. Kortshagen et al, Department of Mechanical Engineering Quantum dots fluoresce in visible range, color determined by size Brighter than conventional indicator dyes, won t bleach However, commonly made from toxic materials Kortshagen group makes silicon QDs biocompatible and safer

24 MEMS Muscle Force Sensor R. Rajamani et al, Department of Mechanical Engineering Muscle Force Sensor for Patients with Neuromuscular Diseases

25 Passive Wireless System for Biosensing R. Rajamani, S. Sezen, P. Peng, S. Sivaramakrishnan, U Minnesota Surface acoustic wave-interdigital transducer (SAW-IDT) Passive wireless telemetry for bio-acoustic sensors. Applications: monitoring breathing sounds in apnea patients monitoring chest sounds after cardiac surgery use in neonatal care units for monitoring chest sounds of newborns

26 Compact Power Sources Thin film Li-ion batteries Deposited onto Si, flexible plastic, or other substrates Rechargeable, very compact Commercialized

27 Microfluidics-Based Systems to Study Cellular Biology Christy L. Haynes (PI), Donghyuk Kim, and Xiaojie Wu, Department of Chemistry A platform to investigate: cell movements under different chemical stimuli adhesion of platelets after exposure to silica nanoparticles. High nanoparticle doses found to increase platelet adhesion and aggregation on an endothelial cell layer.

28 Microfluidic Simulations of Sickle Cell Disease D. Wood (PI), X. Lu, C. Jonas, and S. Bening, Department of Biomedical Engineering Using microfluidic devices to simulate real physiological conditions to study sickle cell and other vascular diseases

29 Device to Measure Touch Sensation in Feet and Hands William R. Kennedy, Department of Neurology. BUMPS : a medical device to quantify touch sensation on finger and toe pads. A quick screening method for neuropathy Subjects rub a finger over 5 colored circles to locate a tiny particle (bump), one particle per square. Physiological results from Bumps Tests correlate with structural changes of the Meissner receptor organs Bumps test Meissner receptor organs

30 Nanowire Sensors Prof. Beth Stadler, Department of Electrical and Computer Engineering Magnetostrictive wire arrays Wires nm in diameter As wires resonate, generate magnetic fields electric signals via GMR sensors May be used to sense sound waves: artificial cilia

31 More Nanotechnology Research For more complete research summaries, visit our website, nano.umn.edu Recent work in: Nanomaterials Nanodevices Biomedical device-related work

32 Working with Us Assisted Project: MNC as a solution provider We collaborate on process development, produce product, iterate product development Do It Yourself: MNC as an equipment provider We maintain equipment and labs, provide training, and advise on process After training, your staff runs the experiments on MNC instruments Pilot Production: MNC as a prototype / limited production provider

33 For more info nano.umn.edu James Marti Minnesota Nano Center Phone: (612)