Nanomedicine, Volume I: Basic Capabilities
© 1999 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999
4.4.4 Isotope Discrimination
It will often be useful in nanomedicine to distinguish molecules containing different isotopes of the same chemical elements, for example to count the number of organic molecules in a sample that contain radioactive C14 atoms in place of stable C12 atoms or to make direct assays of heavy radiometal-contaminated tissues. Nanodevices may also sort isotopically heteronuclear molecules into homonuclear fractions, for example to separate deuterochemicals from hydrochemicals or to acquire isotopically pure materials with which to construct:
a. small, high-speed rotors with precisely balanced mass distributions;10
b. components with extremely fine size differences (Section 3.5.6);
c. nanostructures with maximum thermal conductivity (Table 4.1), or mixed isotopes to reduce thermal conductivity (Section 6.3.4.4 (D)); or
d. long-lived isotopically pure structures that generate no internal radioactivity, thus promoting longer device lifetimes (Chapter 13).
The most reliable sensor for discriminating among isotopes within target molecules is the single-proton massometer (Section 4.4.3). Isotopes of any chemical element differ in mass by at least ~1 neutron (~protonic) increments. Thus a massometer with single-proton resolution can resolve all isotopes starting from chemically pure samples. Isobars (atoms having the same mass number) and isotones (atoms having the same number of neutrons) may be finally resolved chemically; nuclear isomers differing in mass by ~0.001 amu cannot be resolved. Teragravity centrifugation (Section 3.2.5) and time-of-flight particle-beam deflection techniques (Section 4.7.1) may also prove useful.
Isotopes vary in many subtle ways due to their mass differences, although it is not yet clear how a potential isotope nanosensor might exploit some or all of these distinctions:
A. Line Shifts -- The electronic energy states of atoms or molecules depend on the reduced nuclear mass, causing a spectral line shift of ~1.0005 between hydrogen and deuterium, less among heavier isotopes, detectable spectroscopically.
B. Hyperfine Structure -- Isotopes differ in electrical quadrupole moment, nuclear spin and magnetic moment, giving rise to hyperfine structure in the optical spectra, especially in the heavier elements. For example, the magnetic moments of hydrogen and deuterium (2.79268 and 0.857387 nuclear magnetons, respectively) are distinguishable via NMR (Section 4.8.3). The NMR frequency in a 10 kilogauss magnetic field is 42.5759 MHz for H, 6.53566 MHz for D. Of course, not all isotopes are NMR sensitive.
C. Vibrations and Rotations -- Molecular spectra are especially sensitive to isotopic changes, since the quanta of vibrational and rotational energies are directly dependent upon the masses of the atoms involved, and there are also some subtle effects from differences in nuclear spin. Separations are commonly achieved by laser excitation.
D. Cross-Sections -- Isotopes have different thermal neutron capture cross sections; for instance, the cross-section of C12 is 3.7 x 103 barns (1 barn = 10-24 cm2) compared to 9 x 10-4 barns for C13 and <10-6 barns for C14. (Electron scattering might be better, since the electron is less likely to cause the nucleus to fission and it is generally difficult to use neutrons to probe samples on the molecular scale.) Similarly, the neutron cross-section for H2O is 0.6 barns compared to 9.2 x 10-4 barns for D2O.
E. Other Properties -- Isotopes differ slightly in various bulk properties, many of which could be measured in submicron-scale aliquots by nanosensors. The ability of both large mammals and micron-size photosynthetic plant cells to preferentially concentrate C12 or C13 in organic matter,1094 and the predicted ability of carbon nanotubes to selectively extract tritium from low-concentration H2-T2 mixtures,3046 constitute proofs of principle that at least some of the bulk properties listed in Table 4.1 may become useful in achieving nanoscale isotopic separation or purification.
Last updated on 19 February 2003