DISCOVER MOLECULAR INTERACTIONS

The principal functional elements of switchSENSE® are DNA nanolevers,
which can be electrically actuated to oscillate at high frequencies.

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Measurement
modes.

The switchSENSE® 
principle.

The principal functional elements of switchSENSE® are DNA nanolevers,
which can be electrically actuated to oscillate at high frequencies.

The high frequency dynamic electrical switching mode probes the hydrodynamic friction of analyte molecules and serves to determine the size and shape of biomolecules. When analytes bind to oscillating DNA nanolevers on the sensor spots, the nanolever movement is slowed by the additional friction imposed by the analyte, thereby revealing its size or shape changes.

 

The fluorescence proximity sensing mode detects the binding of molecules in real-time through changes in the dye`s local environment.

The unique use of two different fluorophores makes it possible to monitor two independent signals from two interactions at the same time and on the same sensor spot. It also enables fluorescence resonance energy transfer (FRET) experiments, for binding and conformation analyses that require the resolution of intra-molecular distance changes with sub-nm resolution.

 

Nanolever switching
dynamics
measurements.

Measurement of the electrically actuated DNA nanolever motion. Left: Low alternating voltages repel (attract) the nanolever from (to) the sensor. The fluorescence brightness indicates the nanolever orientation, because energy transfer gradually quenches the fluorescence emission when the dye approaches the gold sensor. Right: Time-resolved nanolever switching dynamics. Analyte molecules binding to the nanolever alter the friction and/or the local chemical environment of the dye, which is detected as changes in the switching speed and/or fluorescence intensity.

Protein friction measurement: 
size and conformation.

switchSENSE® is the only biosensor capable of measuring molecular dynamics on a chip, ideally suited for the analysis of protein sizes and conformations.

The measured instantaneous velocity of the nanolever depends on the hydrodynamic friction of the analyte and hence reveals protein size and conformation.

Unparalled sensitivity and accuracy for protein sizing
switchSENSE® delivers unrivaled accuracy in the size range between 1 and 25 nm, which is crucial when dealing with proteins and macromolecular complexes. Changes in hydrodynamic diameters as small as 0.1 nm can be resolved.

Low Sample Consumption
5 pmol of protein per measurement, i.e., 1/1000th the amount required for a DLS measurement.

Any environment
High or low salt, high or low viscosity, high or low pH.

“Give me a lever long enough […] and I shall move the world.”
Well put, Archimedes!
We designed the Adapter Chip to fit any kind of lever. Short and slender for small proteins, long and rigid for large proteins or protein complexes.

Turnkey conformational
change
analysis.

heliX® measures conformational changes in real-time by directly comparing the hydrodynamic friction (switching speed) of two molecules on two adjacent sensor spots.

Conformational changes are expressed as %-friction-change, which works for any protein or nucleic acid state in almost any environment. Hence, molecular conformations can be investigated early in the discovery process, without previous knowledge about a sample.

Simply define your initial state and measure change.
Anything may serve as a reference, for instance:

  • bare DNA nanolevers without attached proteins
  • the protein conformation before small molecule binding
  • a protein mutant that cannot undergo conformational changes
  • a surrogate protein
  • a particular DNA or RNA fold

Videos.

switchSENSE® explained.
Follow us on 🎬 YouTube for more content. 

Protein Size. Different Size =
Different Switching Speed

 

switchSENSE® Fluorescence Proximity Sending (static mode)

 

switchSENSE®
Antibody Sensing

 

Functional principle of the unique switchSENSE® technology

 

switchSENSE® 
Dynamic Response Sensing

 

switchSENSE®
Conformational Changes

 

switchSENSE®
Bispecific Antibodies

 

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