About us

We are a research group in the School of Engineering and Applied Sciences and the Department of Physics at Harvard University. We do experiments to understand how complex systems such as interacting nanoparticles or proteins spontaneously order themselves — a process called self-assembly or self-organization. We use optical techniques that we develop in our lab to observe both natural systems (such as viruses) and synthetic ones (such as colloidal particles, perhaps dressed up with some interesting biomolecules) in three dimensions and on short time scales. We use the results of these studies to make useful materials and to gain a deeper understanding of the physics of assembly, organization, and life.

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Latest news

Congratulations Dr. Dimiduk!

August 16, 2016

After an engaging talk, full of jokes about physicists and the spherical approximations they like to make, Tom's committee quickly concluded their discussions, letting him know that the defense of his thesis, "Holographic Microscopy for Soft Matter and Biophysics," had been successful. Congratulations Dr. Dimiduk!

A poem inspired by the lambda phage

August 9, 2016

Amanda Auerbach, a PhD Candidate at Harvard in the Department of English, recently published a poem, "The Eve Virus," inspired by the lab's virus physics project. Amanda's poem follows the lysogenic and lytic life cycle of the lambda phage from a unique perspective.

Congratulations Dr. Wang!

Congratulations Dr. Wang!

May 11, 2016

After concluding her thesis defense with an exciting grand finale, "The Self-Assembly of Man," Anna's committee emerged from their discussions quickly. They greeted her with smiles and handshakes, letting her know that her defense of her thesis, "Out-of-Equilibrium Dynamics of Colloidal Particles at Interfaces" had been successful. Congratulations Dr. Wang!

Recent Publications

Goldfain, A. M. ; Garmann, R. F. ; Jin, Y. ; Lahini, Y. ; Manoharan, V. N. Dynamic Measurements of the Position, Orientation, and DNA Content of Individual Unlabeled Bacteriophages. The Journal of Physical Chemistry B 2016, 120, 6130–6138. Publisher's VersionAbstract

A complete understanding of the cellular pathways involved in viral infections will ultimately require a diverse arsenal of experimental techniques, including methods for tracking individual viruses and their interactions with the host. Here we demonstrate the use of holographic microscopy to track the position, orientation, and DNA content of unlabeled bacteriophages (phages) in solution near a planar, functionalized glass surface. We simultaneously track over 100 individual λ phages at a rate of 100 Hz across a 33 μm × 33 μm portion of the surface. The technique determines the in-plane motion of the phage to nanometer precision, and the height of the phage above the surface to 100 nm precision. Additionally, we track the DNA content of individual phages as they eject their genome following the addition of detergent-solubilized LamB receptor. The technique determines the fraction of DNA remaining in the phage to within 10% of the total 48.5 kilobase pairs. Analysis of the data reveals that under certain conditions, λ phages move along the surface with their heads down and intermittently stick to the surface by their tails, causing them to stand up. Furthermore, we find that in buffer containing high concentrations of both monovalent and divalent salts, λ phages eject their entire DNA in about 7 s. Taken together, these measurements highlight the potential of holographic microscopy to resolve the fast kinetics of the early stages of phage infection.

Wang, A. ; Garmann, R. F. ; Manoharan, V. N. Tracking E. coli runs and tumbles with scattering solutions and digital holographic microscopy. Opt. Express 2016, 24, 23719–23725. Publisher's VersionAbstract

We use in-line digital holographic microscopy to image freely swimming E. coli. We show that fitting a light scattering model to E. coli holograms can yield quantitative information about the bacterium&\#x02019;s body rotation and tumbles, offering a precise way to track fine details of bacterial motility. We are able to extract the cell&\#x02019;s three-dimensional (3D) position and orientation and recover behavior such as body angle rotation during runs, tumbles, and pole reversal. Our technique is label-free and capable of frame rates limited only by the camera.

Dimiduk, T. G. ; Manoharan, V. N. Bayesian approach to analyzing holograms of colloidal particles. Opt. Express 2016, 24, 24045–24060. Publisher's VersionAbstract

We demonstrate a Bayesian approach to tracking and characterizing colloidal particles from in-line digital holograms. We model the formation of the hologram using Lorenz-Mie theory. We then use a tempered Markov-chain Monte Carlo method to sample the posterior probability distributions of the model parameters: particle position, size, and refractive index. Compared to least-squares fitting, our approach allows us to more easily incorporate prior information about the parameters and to obtain more accurate uncertainties, which are critical for both particle tracking and characterization experiments. Our approach also eliminates the need to supply accurate initial guesses for the parameters, so it requires little tuning.

Rogers, W. B. ; Shih, W. M. ; Manoharan, V. N. Using DNA to Program the Self-Assembly of Colloidal Nanoparticles and Microparticles. Nature Reviews Materials 2016. Publisher's VersionAbstract

DNA is not just the stuff of our genetic code; it is also a means to design self-assembling materials. Grafting DNA onto nano- and microparticles can, in principle, ‘program’ them with information that tells them exactly how to self-assemble. Although fully programmable assembly has not yet been realized, the groundwork has been laid: with an understanding of how specific interparticle attractions arise from DNA hybridization, we can now make systems that reliably assemble in and out of equilibrium. We discuss these advances, and the design rules that will allow us to control — and ultimately program — the assembly of new materials.

Chomette, C. ; Duguet, E. ; Mornet, S. ; Yammine, E. ; Manoharan, V. N. ; Schade, N. B. ; Hubert, C. ; Ravaine, S. ; Perro, A. ; Treguer-Delapierre, M. Templated growth of gold satellites on dimpled silica cores. Faraday Discuss. 2016, 191, 105-116. Publisher's VersionAbstract
We synthesize robust clusters of gold satellites positioned with tetrahedral symmetry on the surface of a patchy silica core by adsorption and growth of gold on the patches. First we conduct emulsion polymerization of styrene in the presence of 52 nm silica seeds whose surface has been modified with methacryloxymethyltriethoxysilane (MMS). We derive four-dimple particles from the resulting silica/polystyrene tetrapods. Polystyrene chains are covalently bound to the silica surface within the dimples due to the MMS grafts and they may be thiolated to induce adsorption of 12 nm gold particles. Using chloroauric acid, ascorbic acid and sodium citrate at room temperature, we grow gold from these 12 nm seeds without detachment from or deformation of the dimpled silica surface. We obtain gold satellites of tunable diameter up to 140 nm.
Faez, S. ; Latin, Y. ; Weidlich, S. ; Garmann, R. F. ; Wondraczek, K. ; Zeisberger, M. ; Schmidt, M. A. ; Orrit, M. ; Manoharan, V. N. Fast, label-free tracking of single viruses and weakly scattering nanoparticles in a nanofluidic optical fiber. ACS Nano 2015, 9 12349-12357. Publisher's VersionAbstract

High-speed tracking of single particles is a gateway to understanding physical, chemical, and biological processes at the nanoscale. It is also a major experimental challenge, particularly for small, nanometer-scale particles. Although methods such as confocal or fluorescence microscopy offer both high spatial resolution and high signal-to-background ratios, the fluorescence emission lifetime limits the measurement speed, while photobleaching and thermal diffusion limit the duration of measurements. Here we present a tracking method based on elastic light scattering that enables long-duration measurements of nanoparticle dynamics at rates of thousands of frames per second. We contain the particles within a single-mode silica fiber having a subwavelength, nanofluidic channel and illuminate them using the fiber’s strongly confined optical mode. The diffusing particles in this cylindrical geometry are continuously illuminated inside the collection focal plane. We show that the method can track unlabeled dielectric particles as small as 20 nm as well as individual cowpea chlorotic mottle virus (CCMV) virions—26 nm in size and 4.6 megadaltons in mass—at rates of over 3 kHz for durations of tens of seconds. Our setup is easily incorporated into common optical microscopes and extends their detection range to nanometer-scale particles and macromolecules. The ease-of-use and performance of this technique support its potential for widespread applications in medical diagnostics and micro total analysis systems.

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Contact

Manoharan Lab
McKay 530
9 Oxford St.
Cambridge, MA 02138
+1 (617) 495-9894
vnm@seas.harvard.edu

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