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20.309: Biological Instrumentation and Measurement


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Single cell analysis

  1. Love, et al., "A microengraving method for rapid selection of single cells producing antigen-specific antibodies" Nature Biotechnology 2006.
  2. Akagi, et al., "Cell electrophoresis on a chip: what can we know from the changes in electrophoretic mobility?" Anal Bioannal Chem 2008.
  3. Gratton, et al., "The effect of particle design on cellular internalization pathways" PNAS 2008.
  4. Sakaue-Sawano, et al., "Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression" Cell 2008.
  5. Tzur, et al., "Cell Growth and Size Homeostasis in Proliferating Animal Cells" Science 2009.
  6. Di Talia, et al., "The effects of molecular noise and size control on variability in the budding yeast cell cycle" Nature 2007.
  7. Spencer, et al., "Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis" Nature 2009.
  8. Shalby, et al., "A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum infected erythrocytes" PNAS 2002.

Metastasis and Circulating Tumor Cells

  1. Norton and Massague, "Is cancer a disease of self-seeding?" Nature Medicine 2006.
  2. Nagrath, et al., "Tumor cells caught in the act of invading: their strategy for enhanced cell motility" TRENDS in Cell Biology 2005.
  3. Nagrath, et al., "Isolation of rare circulating tumour cells in cancer patients by microchip technology" Nature 2007.
  4. Talasaz, et al., "Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device" PNAS 2009.
  5. Maheswaran, et al., "Detection of Mutations in EGFR in Circulating Lung-Cancer Cells" NEJM 2008.

Biomolecular detection

  1. Mettetal, et al., "The Frequency Dependence of Osmo-Adaptation in Saccharomyces cerevisiae" Science 2008. supp info
  2. J. W. Hong, et al. "A nanoliter-scale nucleic acid processor with parallel architecture," Nature Biotech. 22(4): pp. 435-439 (2004).
  3. Winklelman, et al. "Density-Based Diamagnetic Separation: Devices for Detecting Binding Events and for Collecting Unlabeled Diamagnetic Particles in Paramagnetic Solutions" Analytical Chemistry 2007.
  4. Kong, et al., "Parallel gene synthesis in a microfluidic device" Nucleic Acids Research 2007.
  5. E. Winfree, et al. "Design and self-assembly of two-dimensional DNA crystals," Nature 394(6693): pp. 539-544 (1998). OR P. W. K. Rothemund "Folding DNA to create nanoscale shapes and patterns," Nature 440(7082): pp. 297-302(2006).
  6. Maerkl and Quake, "A Systems Approach to Measuring the Binding Energy Landscapes of Transcription Factors" Science 2007.
  7. L Warren, et al. "Transcription factor profiling in individual hematopoietic progenitors by digital RT-PCR" Proc. Nat. Acad. Sci. 2006. OR E.A. Ottesen et al. "Microfluidic Digital PCR Enables Multigene Analysis of Individual Environmental Bacteria" Science 2006.
  8. J. M. Nam, C. S. Thaxton, C. A. Mirkin "Nanoparticle-based bio-bar codes for the ultrasensitive detection of proteins," Science 301(5641): pp. 1884-1886 (2003).
  9. Clack et al. "Electrostatic readout of DNA microarrays with charged microspheres," Nature Biotechnology 2008.
  10. Fan et al. "Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood," Nature Biotechnology 2008.
  11. Naik et al. "Towards single-molecule nanomechanical mass spectrometry," Nature Nanotechnology 2009.

Scanning probe microscopy

  1. A. Engell and D. J. Muller "Observing single biomolecules at work with the atomic force microscope," Nature Stuct. Biol. 7(9): pp. 715-718 (2000).
  2. G. E. Fantner et al. "Sacrificial bonds and hidden length: Unraveling molecular mesostructures in tough materials" Biophys. J 90(4): pp. 1411-1418 (2006).
  3. SY Lee et al. "Chemomechanical mapping of ligand-receptor binding kinetics on cells" PNAS 104: pp. 9609-9614 (2007).
  4. MJ Rosenbluth, WA. Lam, and DA Fletcher, “Force Microscopy of Nonadherent Cells: A Comparison of Leukemia Cell Deformability” Biophysical Journal 90: pp. 2994-3003 (2006).
  5. I. Rousso et al., "Microsecond atomic force sensing of protein conformational dynamics: Implications for the primary light-induced events in bacteriorhodopsin," PNAS 94, pp. 7937-41 (1997).
  6. F. Schwesinger et al. "Unbinding forces of single antibody-antigen complexes correlate with their thermal dissociation rates" PNAS 97(18): pp. 9972-9977 (2000).
  7. F. Dupres et al. "Nanoscale mapping and functional analysis of individual adhesins on living bacteria" Nature Methods 2005.

Optical Microscopy: Imaging

  1. Z. E. Perlman et al., "Multidimensional Drug Profiling by Automated Microscopy," Science 306 pp. 1194-98 (2004).
  2. E. Chung, D. Kim, and P. T. C. So, "Extended resolution wide-field optical imaging: objective-launched standing-wave total internal reflection fluorescence microscopy," Opt. Lett. 31(7) pp. 945-7 (2006).
  3. T. Ichimura et al., "Application of tip-enhanced microscopy for nonlinear Raman spectroscopy," Appl. Phys. Lett. 84(10), pp. 1768-70 (2004).
  4. T-W. Koo, S. Chan, and A. A. Berlin, "Single-molecule detection of biomolecules by surface-enhanced coherent anti-Stokes Raman scattering," Opt. Lett. 30(9), pp. 1024-6 (2005).
  5. M. J. Rust, M. Bates, X. Zhuang, "Sub-diffraction-limit imaging by stochastic reconstruction optical microscopy (STORM)," Nature Methods 3:793-795 (2006).
  6. Design of Fluorescence Wide Field Microscopy

Optical Microscopy: Biomechanics

  1. S. M. Block et al., "Probing the kinesin reaction cycle with a 2D optical force clamp," PNAS 100(5), pp. 2351-56 (2003).
  2. P. J. Verveer et al., "Quantitative Imaging of Lateral ErbB1 Receptor Signal Propagation in the Plasma Membrane," Science 290 pp. 1567-70 (2000).
  3. S. Yamada, D. Wirtz, and S. C. Kuo, "Mechanics of Living Cells Measured by Laser Tracking Microrheology," Biophys. J 78(4), pp. 1736-47 (2000).
  4. B. Yap and R. D. Kamm, "Cytoskeletal remodeling and cellular activation during deformation of neutrophils into narrow channels," J Appl. Physiol. 99, pp. 2323-30 (2005).
  5. J. C. Crocker et al., "Two-Point Microrheology of Inhomogeneous Soft Materials," Phys. Rev. Lett. 85(4), pp. 888-91 (2000).
  6. C. S. Chen et al., "Geometric control of cell life and death," Science 276 pp. 1425-28 (1997).
  7. Y. Wang et al., "Visualizing the mechanical activation of Src," Nature 434, pp. 1040-45 (2005).

Optical Trapping and 3D Imaging

  1. Khalil, A.S., et al., "Single M13 bacteriophage tethering and stretching." Proceedings of the National Academy of Sciences 104, pp. 4892-4897 (2007).
  2. D. Axelrod, "Total Internal Reflection Fluorescence Microscopy in Cell Biology," Traffic 2 pp. 764-774 (2001).
  3. Brau, R.R., et al., "Passive and active microrheology with optical tweezers." Journal of Optics A: Pure and Applied Optics 9, pp. S103-S112 (2007).
  4. Y. Nakayama, et al., "Tunable nanowire nonlinear optical probe." Nature 447, pp. 1098-1101 (2007).
  5. JM. Walter, et al., "Light-powering Escherichia coli with proteorhodopsin" Proceedings of the National Academy of Sciences 104, pp. 2408–2412 (2007).
  6. M. J. Miller et al., "Two-Photon Imaging of Lymphocyte Motility and Antigen Response in Intact Lymph Node," Science 296 pp. 1869-73 (2002).
  7. H. Wang et al., "Coherent Anti-Stokes Raman Scattering Imaging of Axonal Myelin in Live Spinal Tissues," Biophys. J 89(1), pp. 581-91 (2005).
  8. K. M. Hanson et al., "Two-Photon Fluorescence Lifetime Imaging of the Skin Stratum Corneum pH Gradient" Biophys. J 83(3) pp. 1682-90 (2002).
  9. P. J. Campagnola et al., "Three-Dimensional High-Resolution Second-Harmonic Generation Imaging of Endogenous Structural Proteins in Biological Tissues," Biophys. J 81(1) pp. 493-508 (2002).


Presentation time should be 10 minutes (it's very important that you do not go over this time). We will have 5 minutes for questions and discussion. It's also important that all non-presenters read the papers carefully before the session as this will make the discussion much more interesting.

Your presentation should provide background to motivate why the research was conducted, describe the key results of the paper (not necessarily all of the results) and the essence of the measurement method, and explain the significance of the results to the general field. Remember that 10 minutes will not be nearly enough time to discuss every aspect of the paper so you will need to identify the most important aspects to include in your presentation.

Make sure to upload a Powerpoint or PDF file of your presentation the day before the meeting so that we can use only one computer to avoid connection problems.

Feel free to see 20.309 staff outside of class to discuss any questions or ideas that you might have about the paper.