| WEEK # | LECTURES | LABS | READINGS |
|---|---|---|---|
| Part I: Electronics (Instructor - Scott Manalis) | |||
| 0 | Course overview, procedures, syllabus, scheduling | Lab orientation and tour, safety, introduction to electronics | |
| 1 | Electronics for DNA analysis; dividers, Thevenin's theorem, impedance and loading, RC circuits RC circuits: transfer functions, Laplace transforms, impedance, RC filters | Lab orientation and tour, safety, introduction to electronics (cont.) Module 0: introduction to electronics |
This brief Diode Primer will be helpful for working on this week's lab.
|
| 2 | Feedback: Black's formula, the loop; Op-amps: "Golden Rules" and circuit examples DNA analysis: SNP detection, chemical equilibrium - K and DeltaG; description of DNA melting lab apparatus | Module 1: measuring DNA melting curves Part I: build optics for DNA melting experiment, build photodiode readout circuit; calibrate fluorescence signal |
SantaLucia, J. "A Unified View of Polymer, Dumbbell, and Oligonucleotide DNA Nearest-Neighbor Thermodynamics." PNAS 95, no. 4 (February 17, 1998): 1460-1465. |
| 3 | Fourier series, integrals, Fourier transform (continuous/discrete) Fourier analysis (cont.) Evening session: student presentations 1 | Module 1: measuring DNA melting curves (cont.) Part II: complete DNA melting curves apparatus; test perfect-match, all-mismatch, and single-base mismatch DNA strands |
FFT Reference Material
Taton, T. A., C. A. Mirkin, and R. L. Letsinger. "Scanometric DNA Array Detection with Nanoparticle Probes." Science 289, no. 5485 (September 8, 2000): 1757-1760. |
| Part II: Mechanics (Instructor - Scott Manalis) | |||
| 4 | Scanning probe microscopy Signals, noise, power spectral density | Module 2: atomic force microscope Part I: AFM alignment and calibration, AFM imaging I | Binnig, G., and C. F. Quate. "Atomic Force Microscope." Physical Review Letters 56, no. 9 (March 3, 1986): 930-933. This helpful link discusses Spectral Leakage when doing spectral analysis. See also the above FFT reference material. |
| 5 | Correlation/convolution, lock-In amplification, linear systems | Module 2: atomic force microscope (cont.) Part II: AFM imaging II; force spectroscopy | Tutorial 1: discrete and continuous signals, digital sampling, summary of Fourier transforms (PDF) Tutorial 2: sampling example in Fourier space (PDF) Convolution clarification examples (PDF) |
| 6 | Equipartition theorem and thermal fluctuations Student presentations 2 | Module 2: atomic force microscope (cont.) Part III: thermal fluctuations of microcantilevers: Boltzmann's constant experiment | |
| Part III: Optics (Instructor - Peter So) | |||
| 7 | Image processing I Image processing II | Image processing with MATLAB® (linked to homework 3) | Mathworks' MATLAB® Matrix Indexing Tutorial
|
| 8 | Physical optics and optical instrumentation: detectors, noise Optical instrumentation: sources, lasers | Optoelectronics: PMT and photon counting (linked to homework 3.5) | Lecture slides (PDF 2) |
| 9 | Introduction to microscopy: geometric optics, lenses, ray tracing Interference and diffraction, resolution in microscopy, Fourier optics | Module 3: fluorescence microscope construction Part I: white light imaging and Fourier optics | Lecture slides Introduction to microscopy: geometric optics, lenses, ray tracing (PDF - 1.1 MB)# Interference and diffraction, resolution in microscopy, Fourier optics (PDF - 1.0 MB)# Online microscopy references |
| 10 | Fluorescence microscopy Active microrheology Evening session: student presentations: session 3 | Module 3: fluorescence microscope construction (cont.) Part II: live-cell imaging - microrheology | Lecture slides (PDF - 3.3 MB)# |
| 11 | Passive microrheology and particle tracking | Module 3: fluorescence microscope construction (cont.) Part III: actin cytoskeleton imaging | MATLAB® scripts for calculating MSD and G* (ZIP) (Courtesy of Maxine Jonas. Used with permission.) (The ZIP file contains: GetGstar.m and GetMSD.m.) Papers referenced in the lab manual Vukusic, P., and J. R. Sambles. "Photonic Structures in Biology." Nature 424 (August 14, 2003): 852-856. Mason, T. G. "Estimating the Viscoelastic Moduli of Complex Fluids using the Generalized Stokes-Einstein Equation." Rheol Acta 39 (2000): 371-378. Lau, A. W. C., et al. "Microrheology, Stress Fluctuations, and Active Behavior of Living Cells." Physical Review Letters 91 no. 19 (7 November 2003): 198101. Three papers about peacock feathers Zi, Jian, et al. "Coloration Strategies in Peacock Feathers." PNAS 100 (2003): 12576-12578. Yoshioka, S., and S. Kinoshita. "Effect of Macroscopic Structure in Iridescent Color of the Peacock Feathers." Forma 17 (2002): 169-181. Kinoshita, S., and Yoshioka. "Structural Colors in Nature: The Role of Regularity and Irregularity in the Structure." ChemPhysChem 6 (2005): 1442-1459. |
| 12 | Optical trapping [Instructor: Prof. Matt Lang] Advanced fluorescence microscopy Evening session: student presentations 4 | Module 3: fluorescence microscope construction (cont.) and experiments Module 4: optical trapping | |
| 13 | 3D microscopy: confocal imaging 3D Microscopy: two-photon microscopy, 3D image processing | Module 4: optical trapping (cont.) 3D imaging and visualization: two-photon microscopy | |
| 14 | Student presentations 5 | 3D image-stack visualization, imageJ | |
Table of Contents
Study Materials
Readings
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This page presents a table of suggested readings for each lecture/lab session, plus slides used in a few lectures in Part III: Optics. Following the table is a list of papers suggested for student oral presentations.
Hong, J. W., et al. "A Nanoliter-scale Nucleic Acid Processor with Parallel Architecture." Nature Biotech 22, no. 4 (2004): 435-439.
Nam, J. M., C. S. Thaxton, and C. A. Mirkin. "Nanoparticle-based Bio-bar Codes for the Ultrasensitive Detection of Proteins." Science 301, no. 5641 (2003): 1884-1886.
Winfree, E., et al. "Design and Self-assembly of Two-dimensional DNA Crystals." Nature 394, no. 6693 (1998): 539-544.
Rothemund, P. W. K. "Folding DNA to Create Nanoscale Shapes and Patterns." Nature 440, no. 7082 (2006): 297-302.
Hou, C. S. J., et al. "Label-free Microelectronic PCR Quantification." Analytical Chemistry 78, no. 8 (2006): 2526-2531.
Lai, R. Y., et al. "Rapid, Sequence-specific Detection of Unpurified PCR Amplicons via a Reusable, Electrochemical Sensor." PNAS 103, no. 11 (2006): 4017-4021.
Engell, A., and D. J. Muller. "Observing Single Biomolecules at Work with the Atomic Force Microscope." Nature Stuct Biol 7, no. 9 (2000): 715-718.
Schwesinger, F., et al. "Unbinding Forces of Single Antibody-Antigen Complexes Correlate with their Thermal Dissociation Rates." PNAS 97, no. 18 (2000): 9972-9977.
Rugar, D., et al. "Single Spin Detection by Magnetic Resonance Force Microscopy." Nature 430, no. 6997 (2004): 329-332.
Verveer, P. J., et al. "Quantitative Imaging of Lateral ErbB1 Receptor Signal Propagation in the Plasma Membrane." Science 290 (2000): 1567-70.
Chen, C. S., et al. "Geometric Control of Cell Life and Death." Science 276 (1997): 1425-28.
Perlman, Z. E., et al. "Multidimensional Drug Profiling by Automated Microscopy." Science 306 (2004): 1194-98.
Wang, Y., et al. "Visualizing the Mechanical Activation of Src." Nature 434 (2005): 1040-45.
Fritz, J., et al. "Translating Biomolecular Recognition into Nanomechanics." Science 288, no. 5464 (2000): 316-318.
Axelrod, D. "Total Internal Reflection Fluorescence Microscopy in Cell Biology." Traffic 2 (2001): 764-774.
Chung, E., D. Kim, D., and P. T. C. So. "Extended Resolution Wide-field Optical Imaging: Objective-launched Standing-wave Total Internal Reflection Fluorescence Microscopy." Opt Lett 31, no. 7 (2006): 945-7.
Van Marion, A. M. W., et al. "Morphology of the Bone Marrow after Stem Cell Transplantation." Histopahology 48 (2006): 329-42.
Fantner, G. E., et al. "Sacrificial Bonds and Hidden Length: Unraveling Molecular Mesostructures in Tough Materials." Biophys J 90, no. 4 (2006): 1411-1418.
Block, S. M., et al. "Probing the Kinesin Reaction Cycle with a 2D Optical Force Clamp." PNAS 100, no. 5 (2003): 2351-56.
Yamada, S., D. Wirtz, and S. C. Kuo. "Mechanics of Living Cells Measured by Laser Tracking Microrheology." Biophys J 78, no. 4 (2000): 1736-47.
Yap, B., and R. D. Kamm. "Cytoskeletal Remodeling and Cellular Activation during Deformation of Neutrophils into Narrow Channels." J Appl Physiol 99 (2005): 2323-30.
Crocker, J. C., et al. "Two-point Microrheology of Inhomogeneous Soft Materials" Phys Rev Lett 85, no. 4 (2000): 888-91.
Rousso, I., et al. "Microsecond Atomic Force Sensing of Protein Conformational Dynamics: Implications for the Primary Light-induced Events in Bacteriorhodopsin." PNAS 94 (1997): 7937-41.
Miller, M. J., et al. "Two-photon Imaging of Lymphocyte Motility and Antigen Response in Intact Lymph Node." Science 296 (2002): 1869-73.
Ichimura, T., et al. "Application of Tip-enhanced Microscopy for Nonlinear Raman Spectroscopy." Appl Phys Lett 84, no. 10 (2004): 1768-70.
Koo, T-W., S. Chan, and A. A. Berlin. "Single-molecule Detection of Biomolecules by Surface-enhanced Coherent Anti-Stokes Raman Scattering." Opt Lett 30, no. 9 (2005): 1024-6.
Wang, H., et al. "Coherent Anti-Stokes Raman Scattering Imaging of Axonal Myelin in Live Spinal Tissues" Biophys J 89, no. 1 (2005): 581-91.
Hanson, K. M., et al. "Two-photon Fluorescence Lifetime Imaging of the Skin Stratum Corneum pH Gradient." Biophys J 83, no. 3 (2002): 1682-90.
Campagnola, P. J., et al. "Three-dimensional High-resolution Second-harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues." Biophys J 81, no. 1 (2002): 493-508.