DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.

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Presentation transcript:

DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003

To directly quantify biomolecular interaction General Goal: Why? “…it has become evident that bimolecular processes are governed by piconewton forces” Receptor-ligand interactions Protein and nucleic acid structures Covalent bonds Examples:

The next goal: To detect single-base pair mismatch using Single-molecular forces measurements ***Previous best was 10 base pairs***

Previous best method used Atomic Force Microscopy AFM or

The cantilever spring method:

Glass slide Rudder stamp The new method (differential force) :

Glass slide Rudder stamp

The single-base pair mismatch challenge: PM > MM Cy5 intensity = strength

Shear Geometry vs. Zip Geometry Have : Identical sequence Binding energies Thermal on/off rates …but the zip 25-mer is 15 fold more likely to rupture!

The Application: A means of discriminating between specific and non-specific antibody antigen interactions Cy3 intensity = strength

False Positive detection: Protein array confirmation Since false positives increase geometrically as the number of spots increases. Could increase specificity

Questions: 1.Data is presented as intensity (probabilities), not forces 2.How complex are the mechanics of the tug-of-war? 3.How useful would it really be for “Precision SNP detection”? 4.Applications for DNA arrays 5.Chip design cost? 6.Cost of synthesizing antibodies couples to oligos on the rubber stamp thing?