Over the years, light scattering from acoustic waves has grown to be increasingly important in the fields of biology and medicine. This type of scattering, known as Brillouin scattering, has already seen a plethora of applications in fields such as physics. However, the potential for Brillouin scattering for medical imaging and diagnostics has only recently been considered. In this work, we summarize most of the applications of Brillouin scattering in biology to date, and some current work in our lab showing how Brillouin scattering is a worthy prospect for many emerging problems in biology and medical diagnostics.

Significance: Tumors are complex systems characterized by spatial heterogeneity at the genetic, molecular, and cellular levels. Tumor heterogeneity is the critical phenomenon determining the difference in therapeutic outcomes for patients with similar histological diagnosis. Metabolic heterogeneity, i.e., the difference in cancer cell metabolism within a tumor and between tumors, is considered to be a negative prognostic factor and is accompanied by an increased probability of recurrence and higher mortality. Detection and quantification of metabolic heterogeneity can help in diagnosing cancer, assessing tumor progression, and optimizing cancer treatment. Here, we demonstrate that fluorescence lifetime imaging with the advanced detection and signal analysis system may allow rapid, sensitive, and noninvasive assessment of cellular metabolic heterogeneity in living cells.

Random lasers are a developing class of light sources that utilize a highly disordered gain medium as opposed to a conventional optical cavity. Although traditional random lasers often have a relatively broad emission spectrum, a random laser that utilizes vibration transitions via Raman scattering allows for an extremely narrow bandwidth, on the order of 10 cm⁻¹. Here we demonstrate the first experimental evidence of lasing via a Raman interaction in a bulk three-dimensional random medium, with conversion efficiencies on the order of a few percent. Furthermore, Monte Carlo simulations are used to study the complex spatial and temporal dynamics of nonlinear processes in turbid media. In addition to providing a large signal, characteristic of the Raman medium, the random Raman laser offers us an entirely new tool for studying the dynamics of gain in a turbid medium.

Brillouin microscopy is an emerging label-free imaging technique used to assess local viscoelastic properties. Quantum-enhanced stimulated Brillouin scattering is demonstrated using low power continuous-wave lasers at 795 nm. A signal-to-noise ratio enhancement of 3.4 dB is reported by using two-mode intensity-difference squeezed light generated with the four-wave mixing process in atomic rubidium vapor. The low optical power and the excitation wavelengths in the water transparency window have the potential to provide a powerful bio-imaging technique for probing mechanical properties of biological samples prone to phototoxicity and thermal effects. The performance enhancement affordable through the use of quantum light may pave the way for significantly improved sensitivity that cannot be achieved classically. The proposed method for utilizing squeezed light for enhanced stimulated Brillouin scattering can be easily adapted for both spectroscopic and imaging applications in biology.

Brillouin scattering has been emerging as a viable tool for microscopy. However, most of the work done has been with the use of spontaneous Brillouin scattering, which has several hindrances to its use. In this work, we propose and demonstrate nonlinear Brillouin scattering as a solution to many of these hindrances. Here we demonstrate fast two-dimensional microscopic optical imaging of materials’ mechanical properties for the very first time (to our knowledge) using nonlinear Brillouin scattering. Impulsive stimulated Brillouin scattering (ISBS) was used in an optical configuration that is capable of providing accurate local assessment of viscoelastic properties faster than conventional Brillouin spectroscopy. This proof-of-principle imaging experiment has been demonstrated for materials of known properties and microfluidic devices. Applications to noninvasive biomedical imaging are discussed. The fast acquisition times and strong signal of ISBS coupled with the ability of Brillouin scattering to easily measure materials’ viscoelastic properties make this an attractive technique for biological use.