Brillouin spectroscopy is a widely used technique to characterize material mechanical properties. However, due to the weakness of its signal, it has remained a point-sample technique for decades and it has not been applied to biological samples. In the past few years, we have pioneered a new way of performing Brillouin spectroscopy, fully parallel, with several-orders-of-magnitude higher efficiency than conventional methods. As a result we have developed Brillouin microscopy which can measure the mechanical properties of samples without contact, noninvasively, and with high 3D spatiotemporal resolution. The principle of the technology is based on Brillouin light scattering mediated by acoustic phonons inherently present in material. Measuring the tiny frequency shift and linewidth of Brillouin spectrum allows determining the viscoelastic properties of the material. Continuous improvement of speed, resolution and sensitivity of Brillouin spectroscopy is a core activity of our lab.
We have recently been able to push the limits of Brillouin microscopy to sub-micron spatial resolutions to map the elasticity of cells and extracellular matrix (ECM) without contact. Based on this breakthrough, we are developing an imaging technology to map intracellular elasticity. Knowing the distribution of elastic modulus within a cell may help understanding the transmission and distribution of forces inside the cell and the deformation experienced by cell regions under an applied force. Brillouin microscopy can be combined with microfluidic devices to control cell-ECM mechanics as well as with other microscopy modalities to map cellular forces and cytoskeleton structures.
Proper visual function is dependent on the mechanical balance between corneal strength and intraocular pressure as well as the mechanical balance between intraocular muscles and crystalline lens stiffness. Loss of corneal strength can drive corneal ectasia and is a major risk factor for refractive surgery. Traditional ophthalmic imaging tools have no way of probing corneal biomechanics. Based on Brillouin imaging, we develop optical probes that can measure changes in tissue elasticity by progression of disease, or in response to treatment and drugs. Using our novel imaging devices both ex vivo and in vivo in the clinic, we are now developing biomechanics-based metrics to improve diagnosis and prognosis of keratoconus, to screen at-risk subjects for post-LASIK ectasia, and to monitor the effects of corneal collagen crosslinking. Regarding the crystalline lens, every person beyond the age of 50 experiences severe decline of accommodation, leading to presbyopia. The age-related stiffening of the lens is believed to play a primary role in the decrease of accommodation power. We study the 3D biomechanical properties of the aging lens to understand the biomechanical and bio-optical principles governing accommodation.
Poor penetration into tissue is a crucial drawback common to most optical tools for biomedicine. Optical imaging through opaque materials has been thought to be fundamentally impossible for many years. Recently, however, great excitement has been triggered by outstanding work that overcame scattering through the memory effect, digital phase conjugation, or wavefront shaping. In this area, we are investigating the correlation properties of light sources and how to properly shape them for deep tissue imaging. Using the so-called "shower-curtain" effect, we recently demonstrated record performances in terms of thickness of tissue penetrated with low-cost optical components and safe levels of light power.