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DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.
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Transcript of DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.
![Page 1: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/1.jpg)
DNA:
A programmable Force Sensor
Hauke Clausen-Schaumann et al. 2003
![Page 2: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/2.jpg)
To directly quantify biomolecular interaction
General Goal:
Why?
“…it has become evident that bimolecular processes aregoverned by piconewton forces”
• Receptor-ligand interactions
•Protein and nucleic acid structures
•Covalent bonds
Examples:
![Page 3: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/3.jpg)
The next goal:
To detect single-base pair mismatch using Single-molecular forces measurements
***Previous best was 10 base pairs***
![Page 4: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/4.jpg)
Previous best method used Atomic Force Microscopy
AFM
or
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![Page 6: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/6.jpg)
The cantilever spring method:
![Page 7: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/7.jpg)
Glass slide
Rudder stamp
The new method (differential force) :
![Page 8: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/8.jpg)
Glass slide
Rudder stamp
![Page 9: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/9.jpg)
The single-base pair mismatchchallenge:
PM > MM
Cy5 intensity = strength
![Page 10: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/10.jpg)
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!
![Page 11: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/11.jpg)
The Application:
A means of discriminating betweenspecific and non-specificantibody antigen interactions
Cy3 intensity = strength
![Page 12: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/12.jpg)
False Positive detection:
• Protein array confirmation
• Since false positives increase geometrically as the number of spots increases.
• Could increase specificity
![Page 13: DNA: A programmable Force Sensor Hauke Clausen-Schaumann et al. 2003.](https://reader031.fdocuments.us/reader031/viewer/2022020208/56649f395503460f94c55f7a/html5/thumbnails/13.jpg)
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?