Fig. 1) Chronological protocols of duplex formation of the lipophilized oligonucleotide 9 with the comlementary oligomer 16 at an artificial lipid bilayer-aq. buffer boundary, followed by four perfusions f a control and 2) o experiment with non-complementary oligonucleotides, 6 and 7. 3D scans of a pure bilayer (left) 3a-d) 2D-and 4) and of the bilayer-inserted duplex 9+16 (right). A novel technique is described which comprises a base-specific DNA dublex formation at a lipid bilayer-H O-2 phase boundary layer. Different probes of oligonucleotides both carrying a double-tailed lipid at the 5'-terminus were incorporated intostable artificial lipid bilayers separating two compartments (cis/trans-channel) of an optically transparent microfluidic sample carrier with perfusion capabilities. Both the cis-and trans-channel are filled with saline buffer. Injection of a cyanine-labeled target DNA sequence, which is complementary to only one of the oligonucleotide probes, into the cis-channel, followed by a through perfusion, leads to an immobilization of the labeled complementary oligonucleotide on the membrane as a detected by single-molecule fluorescence spectroscopy and microscopy. In the case of fluorescent but non-complementary DNA sequences, no immobilized fluorescent oligonucleotide duplex could be detected on the membrane. This clearly verifies a specific duplex formation at the membrane interface. 2'-Deoxyadenosine and Thymidine were N-alkylated withe geranyl and farnesyl moieties. These hydrophobic derivatives, 6a-b, and 6a-b, respectively, represent the first synthetic biomimetic nucleoterpenes and were subsequently 5'-protected and converted into the corresponding 3'-O-phosphoramidites, 5a-b and 8a-b, respectively. The latter were used to prepare a series of lipophilized oligonucleotide dodecamers, a part of which were additionally labeled with indocarbocyanine fluorescent dyes (Cy3 or Cy5), 11-16. The insertion of the lipooligonucleotides into, as well as duplex formation at artificial lipid bilayers was studied by single-molecule fluorescence spectroscopy and fluorescence microscopy.