Reading the phase of light to measure the shape, density, and motion of living cells — label-free, in three dimensions.
Interferometric microscopy reads the phase of light — the minute delay a specimen imposes on a light wave — to image cells and tissues label-free, quantifying their three-dimensional shape, refractive index, and nanometer-scale motion with no stains. The lab pushes two directions: bringing temporal focusing into phase imaging for scanless, high-speed 3D quantitative phase microscopy, and a structured-illumination scheme (dSIM) for fast, large-field volumetric refractive-index imaging; a single-frame tomographic phase cytometer (xSCYTE) extends the toolkit to high throughput. These methods reach applications from single-cell blood diagnostics to the biophysics of biological nanostructures and nuclear mechanics.
Two ways to make quantitative phase imaging faster and reach further into three dimensions — one using temporal focusing, one using structured illumination.
Quantitative phase microscopy turns the tiny delays a cell imposes on light into a label-free map of its structure — but building a depth-resolved 3D image usually means scanning, which is slow. TF-QPM brings temporal focusing — a scanless, whole-field way to select a single depth plane, until now used only for fluorescence — into coherent phase imaging for the first time. A spectrally chirped pulse recompresses to its shortest duration only at the focal plane, so only that plane interferes with the reference while everything above and below decorrelates. The result is single-shot optical sectioning whose thickness is set by the objective (~0.9 µm) rather than the light source, at camera-limited rates up to ~3.7 kHz — about an order of magnitude faster than prior full-field 3D phase microscopy — with ~2 nm axial sensitivity.
Two established 3D phase methods force a trade-off: tomographic phase microscopy is fast but sees only a small field, while dark-field Fourier ptychography covers a large field but is slow (~1 volume/s), with weak, noisy signals and hours-long reconstructions. dSIM (differential structured illumination microscopy) is designed to get both. Two coherent beams — one at a bright-field angle, one at a steep dark-field angle beyond the objective's collection cone — interfere on the sample; the objective rejects the direct dark-field beam, but its weak high-angle scattering rides on the strong bright-field background through heterodyne gain. Subtracting a bright-field-only image isolates that dark-field signal and keeps the object-to-intensity relationship linear, enabling fast, closed-form 3D refractive-index reconstruction over a millimeter-scale field — targeting ~100 volumes/s and 3D image cytometry beyond half a million cells per second.
Where the lab's phase and interferometric imaging assets meet biology — from single-cell blood diagnostics to the physics of biological nanostructures and the mechanics of the cell nucleus.
