We are advancing the frontier of quantum measurement science by exploring the unique properties of entangled photons interacting with fluorescent proteins (FPs) and other fluorophores used in cellular imaging. For example, time-energy entanglement can significantly enhance nonlinear light-matter interactions. Entangled two-photon absorption follows linear rather than the classical quadratic intensity dependence and can be observed at much lower photon fluxes than two-photon absorption in conventional multiphoton microscopy.
We are exploring the fundamental quantum optics underlying the tantalizing possibility of bioimaging with very low photon fluxes. Development of imaging reagents with large cross-sections for interaction with entangled photons and understanding the mechanism of light-matter interaction is a prerequisite. Quantum-enhanced bioimaging may present new modes of spatial and spectral selectivity that could benefit applications in functional imaging. For example, theory predicts that absorption cross-sections are sensitive to quantum light parameters that can be tuned to achieve two-photon transparency. Development of these capabilities may open the way to fascinating possibilities for highly multiplexed multiphoton bioimaging.
An ultrafast optical pump/EXAFS probe experiment can be used to make a "molecular movie." Here, a diatomic ligand is photodissociated from the heme cofactor of a protein, and the resulting time-resolved structural changes detected by EXAFS are shown in the inset.
Advances in x-ray science and technology have resulted in breakthrough discoveries ranging from unraveling the structure of DNA and proteins, to visualizing atoms, molecules, and materials at the nanoscale. By virtue of their short wavelength, x-rays are ideal probes of the nanoworld. They can image small objects and penetrate thick samples, while the presence of elemental absorption edges in the soft x-ray region allow element and chemical-specific imaging. An exciting recent advance is the ability to generate femtosecond x-ray bursts from femtosecond laser-produced plasmas.
We are designing an ultrafast spectrometer for capturing molecular motion using extended x-ray absorption fine structure (EXAFS), which is a powerful tool for studies of metalloproteins in solution and other disordered samples. Static EXAFS, analyzed using multiple-scattering theory, is particularly useful for precisely measuring bond distances when the structure has already been determined using crystallography. Using ultrafast (femtosecond-to-picosecond) x-rays, we will employ time-resolved EXAFS to characterize excited-state structures in protein cofactor and cofactor analogues, to resolve the excited-state structures and “image” the dynamics with molecular- scale space and time resolution.
We are examining two possible experimental methodologies. In both, an optical laser pulse will first be used to initiate chemical dynamics. In the first scheme, monochromatic x-rays (obtained using a crystal monochromator) will be used as a probe. The element- and bond-specific x-ray fluorescence from the target atoms will then be used to follow the structural and functional changes in the molecule. The second approach will be to directly transient changes in x-ray absorption using a broad bandwidth x-ray probe source, and energy dispersive superconducting transition edge detector arrays that can detect a large solid angle and make use of a large bandwidth.
These experiments are being pursued in collaboration with colleagues in JILA and at NIST Boulder Labs. Using the femtosecond time-resolved EXAFS spectroscopic technique supported by EXAFS spectral simulations, we will investigate these questions: What are the time scales and pathways of conformational relaxation? How does this relaxation depend on the nature of the perturbation and on the structure? How does the relxation process depend on the dynamics of the surrounding solvent? By answering these questions, we will gain insight into ultrafast dynamics of the molecular world.