Zhaokai Meng

Background clean-up in Brillouin microspectroscopy of scattering medium

Brillouin spectroscopy is an emerging tool for microscopic optical imaging as it allows for non-contact, non-invasive, direct assessment of the elastic properties of materials. However, strong elastic scattering and stray light from various sources often contaminate the Brillouin spectrum. A molecular absorption cell was introduced into the virtually imaged phased array (VIPA) based Brillouin spectroscopy setup to absorb the Rayleigh component, which resulted in a substantial improvement of the Brillouin spectrum quality.

Dual Raman-Brillouin Microscope for Chemical and Mechanical Characterization and Imaging

We present a unique confocal microscope capable of measuring the Raman and Brillouin spectra simultaneously from a single spatial location. Raman and Brillouin scattering offer complementary information about a materials chemical and mechanical structure, respectively, and concurrent monitoring of both of these spectra would set a new standard for material characterization. We achieve this by applying recent innovations in Brillouin spectroscopy that reduce the necessary acquisition times to durations comparable to conventional Raman spectroscopy while attaining a high level of spectral accuracy. To demonstrate the potential of the system, we map the Raman and Brillouin spectra of a molded poly(ethylene glycol) diacrylate (PEGDA) hydrogel sample in cyclohexane to create two-dimensional images with high contrast at microscale resolutions. This powerful tool has the potential for very diverse analytical applications in basic science, industry, and medicine.

Optimizing signal collection efficiency of the VIPA-based Brillouin spectrometer

Brillouin spectroscopy is an emerging tool for microscopic optical imaging as it allows for noninvasive and direct assessment of the viscoelastic properties of materials. Recent advances of background-free confocal Brillouin spectrometer allows investigators to acquire the Brillouin spectra for turbid samples as well as transparent ones. However, due to strong signal loss induced by the imperfect optical setup, the Brillouin photons are usually immersed in background noise. In this report, we proposed and experimentally demonstrated multiple approaches to enhance the signal collection efficiency. A signal enhancement by > 4 times can be observed, enabling observation of ultra-weak signals.

Seeing cells in a new light: a renaissance of Brillouin spectroscopy

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.

Microscopic coherent Raman imaging using low-cost continuous wave lasers

Significant effort is devoted to improving the instrumentation for stimulated Raman scattering (SRS) microscopy, which plays an important role in non-invasive biomedical optical imaging by providing a chemically specific contrast without relying on fluorescent markers. In this work we employ low-cost continuous wave lasers to achieve highly sensitive SRS imaging suitable for future application in biology, medicine and materials science. We perform microscopic imaging of dimethyl sulfoxide using two independent, commonly used lasers: a diode pumped, intracavity doubled 532 nm laser and a He–Ne laser operating at 632.8 nm. We further demonstrate that SRS imaging using cw laser sources (cwSRS) is advantageous over pulsed laser based SRS, as it eliminates the possibility of sample damage due to exposure to high-intensity light radiation, while substantially reducing the cost and complexity of the setup and keeping a sub-micron spatial resolution.

Stimulated Brillouin Scattering Microscopic Imaging

Two-dimensional stimulated Brillouin scattering microscopy is demonstrated for the first time using low power continuous-wave lasers tunable around 780 nm. Spontaneous Brillouin spectroscopy has much potential for probing viscoelastic properties remotely and non-invasively on a microscopic scale. Nonlinear Brillouin scattering spectroscopy and microscopy may provide a way to tremendously accelerate the data aquisition and improve spatial resolution. This general imaging setup can be easily adapted for specific applications in biology and material science. The low power and optical wavelengths in the water transparency window used in this setup provide a powerful bioimaging technique for probing the mechanical properties of hard and soft tissue.

Subcellular measurements of mechanical and chemical properties using dual Raman‐Brillouin microspectroscopy

Brillouin microspectroscopy is a powerful technique for noninvasive optical imaging. In particular, Brillouin microspectroscopy uniquely allows assessing a samples mechanical properties with microscopic spatial resolution. Recent advances in background-free Brillouin microspectroscopy make it possible to image scattering samples without substantial degradation of the data quality. However, measurements at the cellular- and subcellular-level have never been performed to date due to the limited signal strength. In this report, by adopting our recently optimized VIPA-based Brillouin spectrometer, we probed the microscopic viscoelasticity of individual red blood cells. These measurements were supplemented by chemically specific measurements using Raman microspectroscopy.

Brillouin spectroscopy as a new method of screening for increased CSF total protein during bacterial meningitis.

Bacterial meningitis is a disease of pronounced clinical significance, especially in the developing world. Immediate treatment with antibiotics is essential, and no single test can provide a conclusive diagnosis. It is well established that elevated total protein in cerebrospinal fluid (CSF) is associated with bacterial meningitis. Brillouin spectroscopy is a widely used optical technique for noninvasive determination of the elastic moduli of materials. We found that elevated protein levels in CSF alter the fluid elasticity sufficiently to be measurable by Brillouin spectroscopy, with model healthy and diseased fluids distinguishable to marked significance (P = 0.014), which increases with sample concentration by dialysis. Typical raw output of a 2-stage VIPA Brillouin spectrometer: inelastically scattered Brillouin peaks (arrows) and elastically scattered incident radiation (center cross).

Precise Determination of Brillouin Scattering Spectrum Using a Virtually Imaged Phase Array (VIPA) Spectrometer and Charge-Coupled Device (CCD) Camera.

Brillouin spectroscopy is an emerging tool for microscopic optical imaging as it allows noninvasive assessment of viscoelastic properties of materials. The use of atomic–molecular absorption cells as ultra-narrow notch filters allows acquisition of Brillouin spectra from turbid samples despite their strong elastic scattering. However, such systems alter the shapes of the Brillouin lines, making the precise determination of the Brillouin shift difficult. In this report, we propose a simple method for analyzing the Brillouin spectrum using a customized least-square fitting algorithm. The absorption spectrum induced by the atomic–molecular cell was taken into consideration. The capability of the method is confirmed by processing experimental spectroscopic data from the pure water at different temperatures. The accuracy of the measurements of ±1 MHz spectral line shift is experimentally demonstrated.

Electronically tunable coherent Raman spectroscopy using acousto-optics tunable filter

Fast and sensitive Raman spectroscopy measurements are imperative for a large number of applications in biomedical imaging, remote sensing and material characterization. In this report, by introducing an electronically-tunable acousto-optical filter as a wavelength selector, we demonstrated a novel instrumentation to the broadband coherent Raman spectroscopy. Systems tunability allows assessing Raman transitions ranging from <400 cm(-1) to 4500 cm(-1). We validated the use of the new instrumentation by collecting coherent anti-Stokes spectra and stimulated Raman spectra of various samples.