Nature Protocols Paper on Mad City Labs MicroMirror TIRF System


Nature Protocols has published a paper from researchers at the University of Wisconsin-Madison and Brandeis University about the colocalization single-molecule spectroscopy (CoSMoS) method for studying cellular machines using the Mad City Labs MicroMirror TIRF system.

The technique of micro-mirror TIRF (total internal reflection fluorescence) microscopy is the only proven method to study the ordered assembly and function of multi-component biomolecular machines. The Mad City Labs' MicroMirror TIRF system is part of a single molecule imaging instrument portfolio and draws on Mad City Labs expertise with high precision, high stability nanopositioning systems and microscopy solutions.

The MicroMirror TIRF system uses through-the-objective excitation, but replaces the dichroic used in conventional TIRF systems with two broadband micro-mirrors positioned at the back aperture of the objective lens. The elimination of the dichroic mirror leads to superior signal-to-noise ratios and simplifies the introduction of multiple spectral lines to your experiment. Typical biomolecular systems studied using micro-mirror TIRF incorporate 3 or more laser lines which can be difficult to accomodate in conventional dichroic TIRF instruments.

Each micro-mirror is mounted to a multi-axis precision mount allowing the user to make fine adjustments to the optical pathway. The imaging and motion control platform is designed to maximize optical pathway accessibility and flexibility, while also simplifying theoptical alignment. A compelling advantage of our MicroMirror TIRF system is the open access to the entry and exit optical pathways. The motion control platform comprises an XY micropositioning platform with an integrated XYZ closed loop nanopositioning system. The XYZ closed loop nanopositioning uses proprietary PicoQ® sensors for sub-nanometer precision and high stability. A z-axis micropositioner with integrated sample holder is mounted above the nanopositioning system.

Completing our MicroMirror TIRF system is the TIRF Lock feedback control consisting of a QPD sensor, TIRF Lock controller and software. The TIRF Lock module maintains the TIR signal through software feedback to the nanopositioner.

The MicroMirror TIRF system is an enabling technology for advanced study of complex biomolecular interactions. The MicroMirror TIRF is a proven design and offers a simple yet flexible instrument platform for single molecule research.


  • Integrated imaging & motion control platform
  • Spatially separated excitation & emission beams
  • Adjustable micromirror mounts
  • Open access to optical pathways
  • Highly stable, yet flexible, platform
  • Integrated slide holder
  • TIRF lock feedback control


  • Superior signal-to-noise ratio
  • Eliminates dichroic mirrors
  • Optical pathway accessibility
  • Facilitates multiple laser lines
  • Proven design
  • Enabling technology for studying complex biomolecular interactions
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