Molecular factory on a chip manufactures disease markers for medical
20 December 2005
Researchers have built a programmable chip consisting of tiny fluid
channels, chambers and switches that can manufacture designer chemicals.
In a collaboration between University College Los Angeles (UCLA), the
California Institute of Technology, Stanford University, Siemens and
Fluidigm, the researchers have developed new technology, called an
integrated microfluidic chip. It could simplify, lower the cost and
diversify the types of molecules used to image the biology of disease with
the medical imaging technology, positron emission tomography (PET).
Microchip for production of the disease marker glucose FDG
These molecules are used with PET to search diagnostically throughout the
body to look for, or image, the molecular errors of disease and to guide the
development of new molecular therapeutics.
PET is a new generation of medical imaging for examining the biology of
disease that has been shown to improve dramatically the detection of cancer,
stage the extent of cancer throughout the body, detect recurrence of cancer
and help select the right therapy for individual patients.
In Alzheimer's disease, PET has been shown to be 93 percent accurate in
detecting the disease about three years before the conventional diagnosis of
"probable Alzheimer's" when integrated into the clinical workup of patients.
In addition, PET has been shown to detect Alzheimer's and other
neurological disease years before even symptoms are expressed. PET also is
employed to determine which patients with cardiovascular disease will
benefit from bypass surgery and angioplasty.
These and other clinical uses of PET employ a labeled version of the
sugar glucose, called fluorodeoxyglucose (FDG). Glucose is a critical fuel
for cells throughout the body to perform their normal functions. For
example, 95 percent of the energy for the brain to function comes from
glucose. In addition, cancer cells increase their metabolism of glucose
about 25-fold. There were about 3 million clinical PET studies performed in
clinical services throughout the world in 2005.
Researchers demonstrated a new technology of a programmable chip that can
dramatically accelerate the development of many new molecular imaging
molecules for PET. As a proof of principle, this group of academic and
commercial scientists demonstrated that FDG could be synthesized on a
"stamp-size" chip. These chips have a design similar to integrated
electronic circuits, except they are made up of fluid channels, chambers,
and values, or switches, that can carry out many chemical operations to
synthesize and label molecules for PET imaging. All the operations of the
chip are controlled and executed by a PC.
FDG was produced on the chip and used to image glucose metabolism in a
mouse with a specially designed PET scanner for mice produced by Siemens,
called a microPET. The Science paper illustrates that this technology also
can produce the amount of FDG required for human studies.
More importantly, the paper illustrates a new base technology for
producing and delivering a diverse array of molecular imaging molecules and
labeled drugs for use with PET to examine the biology of many diseases for
molecular diagnostics and to guide the development of new molecular
therapeutics, or drugs.
"Chemists synthesize molecules in a lab by mixing chemicals in beakers
and repeating experiments many times, but one day soon they'll sit at a PC
and carry out chemical synthesis with the digital control, speed and
flexibility of today's world of electronics using a tiny integrated
microfluidic chip," said Hsian-Rong Tseng, assistant professor of molecular
and medical pharmacology, Crump Institute for Molecular Imaging, David
Geffen School of Medicine at UCLA.
There is a vast distribution of manufacturing sites throughout the world
producing PET molecular imaging molecules for hospitals, universities and
pharmaceutical companies. The goal is to integrate these new chips into a
small control device operated by a PC that will be commercially produced,
then to ship chips to users so they can produce whatever molecules they
choose for molecular imaging with PET. These chips will be an enabling
technology to fuel growth in the number and diversity of imaging molecules
and applications of PET in biology and pharmaceutical research and in the
care of patients.
The research was published this week in the journal Science. The research
is supported by a Department of Energy grant to the UCLA Institute for
Molecular Medicine, the National Cancer Institute, the Norton Simon Research
Foundation, a UCLA National Cancer Institute Molecular Imaging Training
grant and commercial support from Siemens and Fluidigm.