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

2. 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:

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

4. Previous best method used Atomic Force Microscopy AFM or

6. The cantilever spring method:

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

8. Glass slide Rudder stamp

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

10. 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!

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

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

13. 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?