High NA objective lens
Floating cover slip
Dilute nanoparticle solution
Targeted cell
The nanoparticle is first trapped by continuous wave optical tweezers. Once in position at the surface of the cell, a pulsed femto-
second beam is applied; this forces the cell through the cell membrane.
motion and nanomanipulation, the biggest market for optical tweezers is in biology. Shortly after Ashkin demonstrated
the first optical tweezers, he made use of
his new tool to make measurements on
cells. This has inspired a huge subfield
of work that looks at both cellular and
molecular properties.
In some of the most remarkable
optical tweezers experiments, researchers have studied the function of single
molecules such as molecular motors. The
Block group in Stanford has achieved
measurements of base pair stepping by
RNA polymerase (RNAP), in which an
RNAP molecule moves along a DNA
molecule; the “steps” taken by the RNAP
molecules are approximately 3 angstroms
in length. This measurement is phenomenally precise: Each displacement is on
the order of the size of a hydrogen atom.
The researchers accomplished this task by
using a 600-nm polystyrene bead. Their
work provides the ultimate example of
the application of optical tweezers and
shows that real insight can be made at
the molecular level.
The field of molecular motor research
is now relatively mature. Work on cells
is perhaps not as developed. However,
as optical physicists start to cross-train
in biology, there is significant growth
in this area. There is a growing body of
work evaluating the properties of blood
cells, as these are relatively easy to trap,
as well as bacteria. Another growth
area is in the spectroscopy of trapped
cells, with the easy combination of
optical tweezers with any spectroscopic
technique that can be put through a
microscope. Raman spectroscopy, which
often involves long integration times, is
of specific interest for those using traps.
An additional advantage is that, with
trapped cells, it becomes easier to probe
sub-cellular and specific sites of interest
on the cell membrane.
the researchers simply measured the
deformability of the cells. No molecular markers are needed—just a simple
mechanical measurement.
Another applied technique that is
being invigorated by optical tweezers is
that of cell poration—which is typically used for drug delivery. This process
primarily involves blasting a cell with
a high-intensity pulse of light, typically from a femtosecond laser source.
Optical techniques are unlikely to have
direct applications for drug delivery in
vivo, but they can open the possibility
of looking at controlled experiments
in vitro and potentially being able to
transfect cell lines that are traditionally
hard to manipulate. In addition to the
transfection of molecular material, these
techniques can also be used to controllably introduce nanoparticles into cells—
another area of great interest for imaging
enhancements and drug delivery.
The technique was developed by
Kishan Dholakia’s group at the University of St. Andrews in Scotland. A gold
nanoparticle is trapped using optical
tweezers and then positioned on the cell
surface and injected into the cell using a
100-fs Ti:sapphire laser. This approach
opens new avenues in cell microrheology
and enhanced Raman spectroscopy,
