Nano-probe™ technology

One other application where Nano-probe technology excels relative to conventional tube or flow NMR probe formats is in the area of heterogeneous samples. One of the early applications demonstrated for the Nano-probe was the acquisition of NMR spectral data for chemically modified polymer beads used in solid-phase-assisted peptide synthesis and related chemical transformations.21 23 When chemically modified beads are interrogated in a conventional NMR sample tube, the resin bead behaves as an insoluble material and at best very broad and poorly resolved spectra may be recorded. In contrast, when the same beads are placed in a Nano-probe and spun at several kHz at the magic angle, there is sufficient solvation of the pendant chemical moiety and the linker to resin bead nucleus to allow the modified portion to behave as if it is in pseudo solution, which allows reasonable NMR spectra to be recorded. Various factors affect the quality of the NMR data that can be obtained for the pendant molecule, which include the tether length and the solvent used for the measurement.23 There have been a diverse assortment of applications of Nano-probe applications reported in the literature that are discussed in further detail in Section 6.3. 

The biological NMR community recognized the potential of Nano-probe technology for dealing with small samples and reported the acquisition of ID and 2D-NMR data for a series of xylosides available in only 10-25 pg quantities using a 500 MHz Nano-probe.189... 

The first by Manzi and Keifer discussed the acquisition of NMR data of microgram quantities of complex carbohydrates using Nano-probe technology.196 Later in 1997, Keifer197 reviewed the utilization of Nano-probe technology in solid-phase synthesis and combinatorial chemistry. 

The only natural product application of Nano-probe technology of which the author is aware in 1998 was the report of the isolation and unambiguous synthesis of cryptolepinone (33) by Bierer and co-workers.201... 

Finally, late in 1999, Delepierre et al.204 reported a comprehensive H-NMR analysis of the Pi7 peptide from the scorpion Panadinus imperator, again using Nano-probe technology to facilitate the acquisition of data with the small samples available. 

Only two reported applications of Nano-probe technology appeared in 2002. The first was a report detailing the solution of the 3D structure of small scorpion toxins present in nano-molar amounts in venom by Delepierre.216 The other report by Wang et a I.2 1 reviewed the application combined application of LC-NMR and Nano-probe technologies for the analysis of mixtures of natural products. 

Various technologies do exist to give still greater sensitivities - perhaps even an order of magnitude greater, e.g., nano probes, 1 mm probes and cryoprobes, but they are currently unusual in a routine NMR environment. These tools tend to be the preserve of the NMR specialist. 

Several applications of 3 mm micro-NMR probe technology were reported in 1994. The first utilized both a 3 mm micro-inverse probe as well as a heteronuclear Nano-probe to acquire the NMR data necessary for the characterization of a 30 pg (0.07 pmol) metabolite sample.59 Following the acquisition of a 13C reference spectrum using a heteronuclear Nano-probe the 40 pL sample from the nano-cell was quantitatively transferred to a 3 mm NMR tube and diluted to a total sample... 

In 1995, the author and co-workers reported a comparison of the 13C-NMR spectra acquired for an 100 pg sample of the alkaloid cryptolepicarboline (13) using both a 3 mm micro-dual and heteronuclear Nano-probes.61 The two probe technologies gave roughly the same s/n ratios with the Nano-probe allowing the acquisition of the spectra in roughly one-third of the time required in a conventional 3 mm probe. Sample volumes were 40 and 140 pL, respectively. 

Abstract. Electroanalytical methods are highly compatible with micro- and nano-machining technology and have the potential of invasive but non-destmctive cell analysis. In combination with optical probes and imaging techniques, electroanalytical methods show great potential for the development of multi-analyte detection systems to monitor in real-time cellular dynamics. 

C. J. Muller, B. J. Vleeming, M. A Reed, J. S. Lamba, R. Hara, L Jones If J. M. Torn, Atomic Probes a Search for Conduction Through a Single Molecule, Nano technology 1996, 7 409-411. 

E.A. Dobisz, F.K. Perkins, and M.C. Peckerar, E beam and proximal probe processes for nano lithography, in Microlithography Science and Technology, J.R. Sheats and B.W. Smith, Eds., p. 737, Marcel Dekker, New York (1998). 

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