SBIR-STTR Award

The Aim is to develop a new instrument that uniquely senses small specific intermolecular interactions. This Bioprobe Force Microscope (BFM) utilizes functionalized biospecific tips and modified atomic force microscopy controller functions. Initial studies strongly suggest we can measure binding forces between adrenoreceptors (BAR), a biomedically important receptor, and an beta-antagonist drug. The Specific Aims of Phase I are to: (1) confirm that we are measuring specific binding forces between receptors and ligands, and (2) functionalize the tip with differing mixtures of receptor/lipid to relate binding forces to receptor density. Phase II will investigate in detail tip characteristics and different receptor tips and perhaps coatings for other purposes; develop software and controller functions; and apply the BFM to real problems in pharmacology and other living science. At the end of the Phase II, we hope to have developed a BFM and various tips which have been demonstrated in a variety of systems to quantitatively study drug/ligand interactions. This would represent the end of the initial stages of basic research. The initial products could then be developed into commercial products as well as into services that ultimately will support a wide variety of investigations. What we have learned should be generalizable to a whole universe of applications in which it is important to have information on the interaction between molecules. PROPOSED COMMERCIAL APPLICATION The BFM should represent a major break- through for investigators in biological, biochemical, biomedical cellular and molecular biologic, medical, pharmacologic including combinatorial chemistry, physiologic, virologic and virtually all living sciences because of its sensitivity in force measurement, high resolution, extremely small sample requirements, and ability to operate in a physiologic environment. The principles will also be useful to the studies of solids, gases and liquids in physics, chemistry, geochemistry and other fields in which nanoscale charge resolution is useful.

Thesaurus Terms:
atomic force microscopy, beta adrenergic receptor, beta antiadrenergic agent, bioengineering /biomedical engineering, biomedical equipment development, receptor binding aminoalcohol, endopeptidase, phosphatidylcholine, propranolol, surface property

The Aim is to further develop and commercialize a new instrument that uniquely senses small specific intermolecular interactions. The Bioprobe Force Microscope (BFM) utilizes functionalized biospecific tips and modified atomic force microscopy controller functions. Phase I found we could measure binding forces between beta-adrenoreceptors (BAR), a biomedically important receptor, and an antagonist drug. The Specific Aims of Phase II are to measure in control and test periods specific binding forces between: (1) membrane proteins, specifically receptors and channels and their ligands, and (2) nonmembrane globular proteins and interacting molecules. Areas have been chosen because of their scientific and clinical potential. Area Resource Persons are experts in these Areas of membrane and globular proteins. They have identified the potential usefulness of the BFM in their area of science and have contributed to the protocols. Phase II focuses on, but is not limited to: (1) membrane proteins including BARs, insulin receptors, oxytocin receptors and sodium channels, and (2) globular proteins including lipoproteins, prions, and proteins that interact with crystals to prevent kidney stones. The principle behind the single product of Phase I has been extended to biomedically important proteins which, in turn, should develop into commercial products and services. The advancements in Phase II will be generalizable to a universe of applications in which it is important to have information on the interaction between molecules. Since Phase I, patent protection has been obtained for the functionalized tips, making the products more attractive commercially. PROPOSED COMMERCIAL APPLICATION The distinctive advantages of AFM technology in the biological force measurement are its extended force range, the ability to make scanning tips biospecific, high spatial resolution, and nanometer control of x, y and z movement. The ability of the biospecific tips, called bioprobes, is to measure the interaction.

Thesaurus Terms:
atomic force microscopy, biomedical equipment development, ligand, receptor binding chemical bond, nanotechnology, surface property bioengineering /biomedical engineering, bioimaging /biomedical imaging