Technical Area/Track 1 Biomedical Imaging and Instrumentation
Focused on imaging, diagnostics, and therapy through biomedical
instrumentation
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Skills Image and signal processing Analog/digital network
analysis Software/hardware programming Circuit Design Data
acquisition Computational analysis of data in regard to living
systems Track 1: Biomedical Imaging and Instrumentation
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E E 445S Real-Time Digital Signal Processing Lab E E 438
Fundamentals of Electronic Circuits E E 312 Software Design and
Implementation I Some Technical Electives BME 357: Biomedical
Imaging Modalities EE 371R: Digital Image & Video Processing
BME 374K: Instrument Design EE 445L: Embedded Systems Lab EE 422C:
Software Design & Implementation II EE 347: Modern Optics BME
347: Fundamentals of BME Optics + 4 hours of Engineering
Electives
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Track 1: Biomedical Imaging and Instrumentation + 4 hours of
Engineering Electives
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Companies Track 1: Biomedical Imaging and Instrumentation
National Instruments Hospira Flextronics GE Healthcare Medtronic
Biomet Stryker Arthrocare Intuitive Surgical Siemens Healthcare
Philips Healthcare Zimmer St. Jude Medical
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Area Faculty Track 1: Biomedical Imaging and Instrumentation
Andrew Dunn Stanislav Emelianov Thomas Milner H. Grady Rylander
Konstantin Sokolov James Tunnell Tim H.C. Yeh Xiaojing John
Zhang
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Very good collection/excitation overlap One project in our lab
uses a combination of radiative and non-radiative techniques:
Multi-Modal Spectroscopy (MMS): Reflectance, Fluorescence, and
Raman Spectroscopy Multiple techniques at once provides
complementary information We aim to use an MMS approach for the
early detection of skin cancer SpectroscopyPhysiology RamanLipids
Beta-carotene N/C ratio Light ScatteringMicroarchitecture
AbsorptionBlood perfusion Hypoxia Water FluorescenceNADH, FAD
Collagen Multi-Modal Spectroscopy for Early Cancer Detection
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Optical fiber probe light source BS spectrograph 1 mm Source:
BBC News, Health contents 2005 Rajaram Appl Opt 2011 N2 Laser Xenon
Lamp Camera SpectrometerOptical switch Microcontroller 830nm laser
Camera Fiber-optic capture Spectrometer Spectral Diagnosis
System
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Probe Performance SIoSIo DI1DI1 ssaa Tissue Optical Fibers
Reflectance Raman Classifier # Lesions RSDOSLIFSCombinedAccuracy MM
vs. PL 12 vs. 17 95 / 89 58/ 41 67 / 18 96 / 91100% BCC vs. N 19
vs. 19 74 / 74 100/ 84 74/ 63 95 / 9595% SCC vs. AK 24 vs. 14 85 /
50 83/ 69 62/ 52 100 / 5784% AKSCC vs. N 52 vs. 52 100/ 54 75/ 64
88/ 64 92 / 7182% PL vs. N 29 vs. 28 90/ 82 97 / 96 93 / 100 97 /
10098% MM = malignant melanoma PL = pigmented lesion BCC = basal
cell carcinoma SCC = squamous cell carcinoma AK = actinic keratosis
AKSCC = AK + SCC N= normal Probe Performance
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Gold nanorod (GNR) properties: Inert and biocompatible Easily
bioconjugable Surface plasmon resonance: Strong absorption and
scattering cross-sections (imaging and therapy) 14 Another project
utilizes Gold Nanorods for Cancer Imaging and Therapy: Image gold
nanorods with two-photon microscopy utilizing a ultrafast fs pulsed
laser to get high axial and lateral resolution Photothermal
therapy, taking advantage of gold nanorods passively and actively
targeted to cancer cells/tumors and using the heat induced from
gold nanorods when excited with laser at nanorod resonance
frequency Gold Nanoparticle-Mediated Imaging and Photothermal
Therapy of Cancer Cells
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15 Nanoparticles Two-photon Imaging (Z-stacks): PEG GNRs (red)
are non- specifically bound to the membrane (green) of the cell
CTAB GNRs (red) are internalized within cells Photothermal Therapy:
Irradiate with near- infrared laser Induce heat Measure cell
damage
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Gold Nanorod Uptake in Multicellular Tumor Spheroids Green:
Cell Membrane Stain Red: Gold Nanorods Blue: Nuclei 3D Cellular in
vitro Models of Cancerous Tumors Optically Magnified Z-Stack 3D
Reconstruction
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Technical Area/Track 1 Biomedical Imaging and Instrumentation
Classes, Opportunities, Post-Grad Final thoughts on
Technical Area/Track 2 Cell and Biomolecular Engineering
Integration of cell & molecular biology with engineering
analysis; Address problems in molecular medicine
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Track 2: Cell and Biomolecular Engineering Skills Tissue
engineering Materials science Construction of nanoscale devices
Creation of bioactive materials Bioengineering perspective on
disease and immune response Modeling biological systems
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BME 339 Biochemical Engineering Track 2: Cell and Biomolecular
Engineering BME 352 Engineering Biomaterials BME 354BME 344BME 379
Some Technical Electives BME 342: Biomechanics of Human Movement
BME 344: Biomechanics BME 354: Molecular Sensors & Nanodevices
for BME Applications BME 379: Tissue Engineering Upper-Division
Biology (Genetics) Organic Chemistry II & Lab + 6 hours of
Engineering Electives
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Track 2: Cell and Biomolecular Engineering + 6 hours of
Engineering Electives
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Track 2: Cell and Biomolecular Engineering Companies Genentech
Merck Pfizer Dow Procter and Gamble Boston Scientific Osteomed
Biomet Amgen Life Technologies GE Terapio
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Track 2: Cell and Biomolecular Engineering Area Faculty Aaron
Baker Amy Brock George Georgiou Jenny Jiang Nicholas Peppas Michael
Sacks Jeanne Stachowiak Laura Suggs Janet Zoldan
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Laboratory of Biomaterials, Drug Delivery and Bionanotechnology
Nicholas A. Peppas
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ORAL PROTEIN DELIVERY 26
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Protein Therapeutics Advantages Complex, unique functions
Faster FDA approval Over 130 approved protein therapeutics 1 In
2010, sales exceeded $93 billion 2 Disadvantages High cost Compound
stability Large molecular weight Route of administration
www.vivo.colostate.edu www.cs.stedwards.edu
www.tarsatherapeutics.com 1 Leader, Benjamin et. al. Protein
therapeutics: A summary and pharmacological evaluation. Nat Rev.
Drug Disc. 7 (2008) 21-39. 2 Maheshwari, Shushmul. Global protein
therapeutics market: Beefing up towards futuristic growth. 27
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Oral Delivery of Therapeutic Proteins Benefits Ease of
administration Increased patient compliance Lower cost Challenges
Maintaining stability and activity in the stomach Narrow absorption
window in the small intestine Transport across endothelium to the
bloodstream 28
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pH-Responsive Systems Complexed; small mesh size pH ~2
Decomplexed; increased mesh size pH ~5-7 29
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Promoting Particle Interaction with the Environment 30
Tether-containing polymer/ drug complexes for mucoadhesion, which
have an increased residence time Caco-2 cells with tight junction
stained Caco-2 cells as a gastrointestinal model Tether-containing
polymer/ drug complexes for mucoadhesion, which have an increased
residence time Caco-2 cells with tight junction stained Caco-2
cells as a gastrointestinal model Tether-containing polymer/ drug
complexes for mucoadhesion, which have an increased residence time
Caco-2 cells with tight junction stained Caco-2 cells as a
gastrointestinal model
A combined approach to oral siRNA delivery 34 Polycationic
polymers mediate endosome disruption through the proton sponge
mechanism. Following endosomal escape, entrapped biomolecules can
be released into the cytosol. PLGA micro- particles Fluorescently-
labeled nanogels after cellular uptake
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MOLECULAR RECOGNITION 35
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Molecularly Imprinted Polymer (MIP) Methodology Used for
diagnostic platforms 36 Solvent Initiator Components
TemplateMolecule FunctionalMonomers Crosslinker Complexation
Polymerization Recognitive Cavity Extraction and drying
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Bionanotechnology 37
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Hydrogels and Heat 38 Gold-polymer nanoparticle for triggered
and targeted drug delivery Upon laser irradiation, a
thermo-sensitive polymer collapses to release therapeutics. Real
time imaging via ultrasound/photoacoustic methods. Temperature
sensitive nano-composites with Fe 3 O 4 and gold NPs shown
schematically, with electron microscopy, and thermal-IR
imaging.
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Technical Area/Track 2 Cell and Biomolecular Engineering
Classes, Opportunities, Post-Grad Final thoughts on
Computational Biomedical Engineering Use of computational
algorithms to address problems in healthcare and biomedical
research
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Skills Design medical decision aids Dynamic analysis of
biomechanics Thermodynamic modeling of bio- molecular reactions
Image processing and interpretation Computational genomics Track 3:
Computational Biomedical Engineering
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M 325K Discrete Mathematics E E 422C Software Design and
Implementation II E E 312 Software Design and Implementation I
Track 3: Computational Biomedical Engineering E E 360C Algorithms
Some Technical Electives BME 341: Engineering Tools for
Computational Genomics Lab BME 342: Biomechanics of Human Movement
BME 344: Biomechanics BME 345: Graphics and Visualization BME 346:
Computational Biomolecular Engineering M 340L: Matrices and Matrix
Calculations + 5 hours of Engineering Electives
Track 3: Computational Biomedical Engineering Kenneth Diller
Mia Markey Pengyu Ren Michael Sacks Area Faculty
Slide 47
Mitral valve (MV) repair: annuloplasty rings Recurrence of
mitral regurgitation after repair due to excessive tissue stress
Multiscale model: valve geometry, tissue stress, MV interstitial
cells Track 3: Computational Biomedical Engineering To develop a
model of the mitral valve that will optimize the restoration of
homeostatic normal tissue stress 3D Reconstruction of MV based on
Micro-CT images 1 1. Lee, Chung-Hao et al.2013
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Track 3: Computational Biomedical Engineering Generation of 3D
Finite Element Model for MV & Estimated Leaflet Thickness based
on Micro-CT Images 1 1. Lee, Chung-Hao et al.2013
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Track 3: Computational Biomedical Engineering To create a 3D
rendition of the MVIC microenvironment using electron microscopy
techniques TEM or SEM 3D reconstruction software: Turboreg, Stagreg
Reconstruct Blender Amira Heymann: 2D & 3D imaging of yeast
cells Heymann et al. 2006