A microscope stage can move with a precision of about 20 nm, but focus correction systems that use a reflected laser beam are diffraction limited to hundreds of nm when locating the surface. Iova Labs builds FREVR (Focus Readjustment for Enhanced Vertical Resolution), a module that holds an optical microscope on its focal plane, or adjusts to any focal plane within a few micrometers, at the precision of its positioning stage (down to 2 nm for piezo stages).
Microscopes drift. As the instrument warms, settles, and responds to the room around it, the focal plane moves.
Even inside an enclosure in a temperature-controlled room, a microscope typically drifts over 1000 nm per hour. Across a four-hour acquisition the focal plane travels micrometers, well past the structures being measured. Super-resolution, single-molecule, and live-cell experiments suffer most, because they run longest and resolve the finest detail. A drifting acquisition is often discovered only after the experiment is over.
FREVR measures the true distance between the objective and the sample up to 1000 times a second, and corrects it in real time. It drives the focus mechanism the microscope already has, so most installations need no new positioning hardware.
The same measurement does more than hold the plane still. FREVR can move the focus to any plane within a few micrometers of the surface and hold it there, at the same resolution it uses to stay put. Those positions can also be revisited. A single acquisition can alternate between the membrane of a cell and a plane inside its nucleus, returning to each depth reproducibly for as long as the experiment runs.
It also handles samples that defeat reflection-based autofocus entirely. Those systems need an optical mismatch at the coverslip to return a signal. Index-matched and cleared preparations are designed to remove exactly that mismatch, so the reflection weakens and the autofocus loses its reference. FREVR reads a fiducial bead rather than an interface, so it does not depend on a boundary the sample preparation is deliberately erasing.
A fiducial bead sits on the sample substrate. Its diffraction pattern changes in a precise, repeatable way as the objective moves along the optical axis. FREVR compares the live pattern against a reference library to determine the true objective-to-sample distance, then corrects it.
Because the measurement is optical and made through the same objective as the experiment, it reflects what the sample is actually experiencing, rather than what a sensor elsewhere in the instrument reports.
Iova Labs is a Wisconsin company founded by two Physics professors at the University of Wisconsin–Milwaukee who spent years building instruments that had to hold focus, and eventually built something that does.
The underlying method was developed in our laboratories and reported in the peer-reviewed literature. It is the subject of a pending patent application held by the UWM Research Foundation, published as international application WO 2026/112137.
We are placing our first units with laboratories running long acquisitions on their own instruments, and we would like to hear from you.
Write to info@iovalabs.org and tell us what you image and how long your experiments run.