Press Release

First Quantum Dots Applied To Living Organism

By SpaceRef Editor
December 2, 2002
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Quantum dots are nano-sized crystals that exhibit all the
colors of the rainbow due to their unique semiconductor
qualities. These exquisitely small, human-made beacons have
the power to shine their fluorescent light for months, even
years. But in the near-decade since they were first readily
produced, quantum dots have excluded themselves from the
useful purview of biology. Now, for the first time, this
flexible tool has been refined, and delivered to the hands of

Quantum dots are about to usher in a new plateau of
comparative embryology, as well as limitless applications in
all other areas of biology.

Two laboratories at The Rockefeller University — the
Laboratory of Condensed Matter Physics, headed by Albert
Libchaber, Ph.D., and the Laboratory of Molecular Vertebrate
Embryology, headed by Ali Brivanlou, Ph.D. — teamed up to
produce the first quantum dots applied to a living organism,
a frog embryo. The results include spectacular three-color
visualization of a four-cell embryo.

The scientists’ results appear in the Nov. 29 issue of

“We always knew this physics/biology collaboration would bear
fruit,” says co-author Brivanlou, “we just never knew how
sweet it would be. Quantum dots in vivo are the most
exciting, and beautiful, scientific images I have ever seen.”

To exploit quantum dots’ unique potential, the Rockefeller
scientists needed to make a crucial modification to existing
quantum dot technology. Without it, frog embryos and other
living organisms would be fallow ground for the physics-based

“Quite simply, we cannot do this kind of cell labeling with
organic fluorophores,” says Brivanlou. Organic fluorophores
(synthetic molecules such as Oregon Green and Texas Red)
don’t have the longevity of quantum dots. What’s more,
organic fluorophores and fluorescent proteins (such as green
fluorescent protein, a jellyfish protein, and luciferase, a
firefly protein) represent a small number of colors, subject
to highly specific conditions for effectiveness. Quantum dots
can be made in dozens of colors just by slightly varying
their size. The application potential in embryology alone is

Hydrophobic, but not claustrophobic

Benoit Dubertret, Ph.D., a postdoctoral fellow working with
Libchaber, toiled for two years with quantum dots’ biggest
problem: their hydrophobic (water-fearing) outer shell. This
condition, a by-product of quantum dots’ synthesis, makes
them repellent to the watery environment of a cell, or
virtually any other biological context.

Since 1993, scientists have tinkered with the organic
ligands, or binding molecules, necessary to the fabrication
of quantum dots’ outer surface, to make them more friendly,
and useful, in biology. Various improvements were successful,
but never foolproof. These included substituting a new ligand
for the hydrophobic one, and overcoating, like painting over,
the existing ligand with human-made surfactants and polymers.

Dubertret is adept at making quantum dots, a volatile
process, which he does through a special research
collaboration between Libchaber’s lab at Rockefeller and NEC,
a research institute in Princeton, N.J.

Working at NEC with another postdoctoral fellow in
Libchaber’s lab, Vincent Noireaux, Ph.D., Dubertret tried a
different approach to the hydrophobia problem. Why not
encapsulate the entire quantum dot with something untried – a-
micelle? The micelle, a simple chemical ligand with two
parts — a hydrophobic head, and a hydrophilic (water-loving)
tail – -did the trick. Drug companies use micelles as a
coating for drugs that have hydrophobic qualities. But no one
had ever thought to use them to contain quantum dots, until
Dubertret and Noireaux thought of it.

“As is often the case in science, it is a little detail that
makes all the difference,” says Libchaber.

“When I saw the micelle engulf the quantum dot in 30 seconds,
folding up in a star-shape that exposed its hydrophilic
section and sealed off its hydrophobic section, I knew we had
succeeded,” says Dubertret. “Other kinds of modifications
were slow going — requiring up to five days of synthesis —
and always had flaws.”

Rather than modifying the final coat of the quantum dot,
Dubertret and his colleagues trapped the quantum dot,
including its hydrophobic coating, inside a new outer

“Now, the outside world does not come into direct contact
with the quantum dot,” says Libchaber. “Instead, the cell
sees only a phospholipid monolayer, an organic type of
surface that is normal to its environs, mixed with ethylene
glycol (PEG), which can be functionalized easily.”

Once the micelles proved stable and durable as a quantum dot
“capsule,” the improved quantum dots were ready to test in a
biology lab.

“Compatible with life”

Quantum dots have numerous potential applications, especially
in biology where visualization is so often a component of the
“readout” of results. The cell lineage and comparative
embryology studies that Brivanlou and his colleagues want to
conduct require large numbers of quantum dots. That’s because
each cell division has to disseminate many quantum dots.

The collaborating team of physicists and molecular
biologists, microinject (inject a large quantity) quantum
dots to very early frog embryos. Though in their first
experiments a single quantum dot was toxic to the embryo,
they purified the quantum dots so that a quantity of 10^9, or
a billion, quantum dots could be injected to a single cell.

The differentiation processes of their rapidly dividing cells
make embryos highly sensitive to physical and chemical
changes in their environment. The Rockefeller scientists are
pleased that such a large number of quantum dots has proven

“We have made the quantum dot compatible with life,” says
Brivanlou. “Each safe application in an organism requires
experimentation. But we’re optimistic that if they work in
frog embryos, they will work in other in vivo contexts.”

The properties of quantum dots make them suitable for
application in many areas from tagging single proteins in
cells to diagnostic imaging.

Brivanlou and one of his graduate fellows, Paris Skourides,
document the improved quantum dots in their experiments via
fluorescence microscopy. In the process, they’ve noted
something new.

“We’ve seen quantum dots dispersed throughout the cytoplasm
of early embryonic cells suddenly relocalize to the nuclei
about four hours after fertilization,” says Skourides. “This
indicates the onset of embryonic transcriptional activity;
visualization with quantum dots is the first in vivo marker
of this important developmental stage.”

During the early stages of Xenopus, or frog, development,
there is no RNA synthesis. In other words, there is no active
rewriting of the information contained in the embryo’s DNA,
and thus no manufacture of proteins needed during
development. Instead the embryo relies on protein and RNA
that the mother provides to the egg. Once the embryo reaches
its 12th cell division (4,000 cells) its own RNA appears, and
transcriptionally speaking, the embryo can fend for itself.

Time-lapse movies from the Brivanlou lab show that the
translocation, the concentration of quantum dots to the
nuclei, occurs at the time known to be consistent with
earliest gene expression of the embryo. (See

Brivanlou and Libchaber together will continue testing
quantum dots. The two scientists are considering many
additional experiments to test their new technology. Still,
they each represent different disciplinary perspectives, and
ask different questions.

Brivanlou and his lab colleagues will pursue safety and
efficacy of quantum dots in vivo, and a variety of other
biological applications questions.

Libchaber and his lab colleagues will study the limits of
detection of quantum dots, including the application of
single quantum dots in biology.

Both lab groups agree, however, that their institutional
milieu set the stage for success.

“The physicists who come to Rockefeller want to interact with
biologists,” says Libchaber. “The program that supports
physics on campus was designed to be this way.”

“Rockefeller is the place where you can bring not just the
technologies, but the thinkers and ideas, together
productively,” says Brivanlou.

This is true in part because the university is a unique
research environment, with no formal departments directing
inquiry. But it is also true because a research center for a
nascent physics- and biology-oriented approach was created in
1994. The Center for Studies in Physics and Biology has been
continuously and enthusiastically supported by the
university’s administration.

“In very few places would it be possible to do this work so
fast,” says Skourides. “The infrastructure for doing
collaborative science is in place.”

Dubertret and Libchaber of the Science publication thank
their Rockefeller colleagues Professor Sandy Simon and
postdoctoral fellow Jyoti Jaiswal, with whom they discussed
quantum dots.

SpaceRef staff editor.