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.

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.

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.

Garmann, R. F. ; Sportsman, R. ; Beren, C. ; Manoharan, V. N. ; Knobler, C. M. ; Gelbart, W. M. A Simple RNA-DNA Scaffold Templates the Assembly of Monofunctional Virus-Like Particles. JACS 2015, 137, 7584–7587. Publisher's VersionAbstract

Using the components of a particularly well-studied plant virus, cowpea chlorotic mottle virus (CCMV), we demonstrate the synthesis of virus-like particles (VLPs) with one end of the packaged RNA extending out of the capsid and into the surrounding solution. This construct breaks the otherwise perfect symmetry of the capsid and provides a straightforward route for monofunctionalizing VLPs using the principles of DNA nanotechnology. It also allows physical manipulation of the packaged RNA, a previously inaccessible part of the viral architecture. Our synthesis does not involve covalent chemistry of any kind; rather, we trigger capsid assembly on a scaffold of viral RNA that is hybridized at one end to a complementary DNA strand. Interaction of CCMV capsid protein with this RNA-DNA template leads to selective packaging of the RNA portion into a well-formed capsid but leaves the hybridized portion poking out of the capsid through a small hole. We show that the nucleic acid protruding from the capsid is capable of binding free DNA strands and DNA-functionalized colloidal particles. Separately, we show that the RNA-DNA scaffold can be used to nucleate virus formation on a DNA-functionalized surface. We believe this self-assembly strategy can be adapted to viruses other than CCMV.

Perry, R. W. ; Holmes-Cerfon, M. C. ; Brenner, M. P. ; Manoharan, V. N. Two-Dimensional Clusters of Colloidal Spheres: Ground States, Excited States, and Structural Rearrangements. Phys. Rev. Lett. 2015, 114, 228301. Publisher's VersionAbstract

We study experimentally what is arguably the simplest yet nontrivial colloidal system: two-dimensional clusters of six spherical particles bound by depletion interactions. These clusters have multiple, degenerate ground states whose equilibrium distribution is determined by entropic factors, principally the symmetry. We observe the equilibrium rearrangements between ground states as well as all of the low-lying excited states. In contrast to the ground states, the excited states have soft modes and low symmetry, and their occupation probabilities depend on the size of the configuration space reached through internal degrees of freedom, as well as a single “sticky parameter” encapsulating the depth and curvature of the potential. Using a geometrical model that accounts for the entropy of the soft modes and the diffusion rates along them, we accurately reproduce the measured rearrangement rates. The success of this model, which requires no fitting parameters or measurements of the potential, shows that the free-energy landscape of colloidal systems and the dynamics it governs can be understood geometrically.

Magkiriadou, S. Structural Color From Colloidal Glasses, 2015. Publisher's VersionAbstract

When a material has inhomogeneities at a lengthscale comparable to the wavelength of light, interference can give rise to structural colors: colors that originate from the interaction of the material's microstructure with light and do not require absorbing dyes. In this thesis we study a class of these materials, called photonic glasses, where the inhomogeneities form a dense and random arrangement. Photonic glasses have angle-independent structural colors that look like those of conventional dyes. However, when this work started, there was only a handful of colors accessible with photonic glasses, mostly hues of blue.

We use various types of colloidal particles to make photonic glasses, and we study, both theoretically and experimentally, how the optical properties of these glasses relate to their structure and constituent particles. Based on our observations from glasses of conventional particles, we construct a theoretical model that explains the scarcity of yellow, orange, and red photonic glasses. Guided by this model, we develop novel colloidal systems that allow a higher degree of control over structural color. We assemble glasses of soft, core-shell particles with scattering cores and transparent shells, where the resonant wavelength can be tuned independently of the reflectivity. We then encapsulate glasses of these core-shell particles into emulsion droplets of tunable size; in this system, we observe, for the first time, angle-independent structural colors that cover the entire visible spectrum. To enhance color saturation, we begin experimenting with inverse glasses, where the refractive index of the particles is lower than the refractive index of the medium, with promising results. Finally, based on our theoretical model for scattering from colloidal glasses, we begin an exploration of the color gamut that could be achieved with this technique, and we find that photonic glasses are a promising approach to a new type of long-lasting, non-toxic, and tunable pigment.



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

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