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C00002 00002 molecu[f82,jmc] Detection of single molecules by methods of
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molecu[f82,jmc] Detection of single molecules by methods of
freshman chemistry
Single molecules can in principle be detected by repeated use
of a sequence of chemical reactions that doubles the amount of a
substance present. In principle, it seems possible to do this
without excessive losses.
Such a sequence might take the following form supposing that
we have some small number (perhaps none) of molecules of a substance AX in water
solution. We wish to determine if there is any AX, and if so how much.
1. We start with a binary reaction
AX + BY → AY + BX.
In order to drive the reaction, there must be a substantial amount of BY
added to the solution.
2. Next we separate AY and BX. This can be done by any standard
chemical method that doesn't depend on the presence of substantial
amounts of AY or BX and tolerates the presence of large amounts of BY.
Imagine that the method is solvent extraction.
3. We now have two containers - one with some (perhaps none) molecules
of AY and the other with some molecules of BX.
Now we use reactions that destroy all the leftover BY with high
probability while leaving AY or BX unchanged. We suppose this
All we need are reactions in which the lifetime of a molecule of BY
is at least 100 times shorter than that of AY or BX. If
the destruction is a Poisson process, this can be done
even though the initial amount of BY is 10↑23 times as large
as the amounts of AY and BX.
4. Next we add to the container with the AY a large amount
of CX and to the container with BX a large amount of AZ. We then
create conditions that drive the reactions
AY + CX → AX + CY
and
BX + AZ → AX + BZ
respectively. Now each container has as much AX as the original
container did.
5. Now we must destroy the excess CX and AZ while
preserving the AX in the two containers.
6. Finally we combine the two containers into the original
container and condense the volume of solvent if necessary to the original
amount. The container now contains twice as much AX as it had
originally.
To go from a molecule of AX to a mole requires that steps
1 thru 5 be carried out 79 times, since 2↑79 = 6 x 10↑23.
Remarks:
1. The key problem is to be sure that no AX is created
except by the desired system of reactions. This may require that
the radicals A and X be relatively complex.
2. A and X should be chosen to make the doubling process
as effective as possible. In order to detect small amounts of a
given substance, we require a preliminary sequence of reactions
that will create one molecule of AX for every molecule of the substance
to be detected. There is no special reason why the substance being
detected should have a composition directly related to AX.
The only requirement is that the conversion reaction not produce
any AX if the substance isn't present.