Microchip Technology for Imaging Biomarkers

A collaboration among scientists has resulted in a new technology that uses integrated microfluidic chips for simplifying, lowering the cost, and diversifying the kinds of molecules used to image disease processes with positron emission tomography (PET) imaging.

These molecules are utilized with PET to diagnostically search throughout the body to look for, or image, the molecular mistakes of disease processes and to channel the development of new molecular therapeutics. PET is a new generation of medical imaging for assessing the biology of disease that has been shown to greatly improve the detection of cancer, stage the extent of cancer throughout the body, identify recurrence of cancer, and help choose the right therapy for individual patients.

In Alzheimer's disease, PET has been shown to be 93% accurate in identifying the disease approximately three years before the traditional diagnosis of "probable Alzheimer's” when integrated into the clinical workup of patients. Furthermore, PET has been shown to detect Alzheimer's and other neurologic disorders long before even symptoms are evident. 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 crucial energy source for cells throughout the body to perform their normal functions. For example, 95% of the energy for the brain to function comes from glucose. Furthermore, cancer cells increase their metabolism of glucose about 25-fold. There were approximately three million clinical PET studies performed in clinical services throughout the world in 2005.

The new technology was developed by a collaboration of investigators from the University of California, Los Angeles (UCLA, USA), the California Institute of Technology (Cal Tech, Pasadena, USA), Stanford University (CA, USA), Siemens Medical Solutions (Erlangen, Germany) and Fluidigm Corp. (South San Francisco, CA, USA).

In the December 16, 2005, issue of the journal Science, the collaborators describe a new technology for a programmable chip that can dramatically speed up 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; however, they are comprised of fluid channels, chambers, and values, or switches, that can perform many chemical operations to synthesize and label molecules for PET imaging. All the functions of the chip are controlled and performed by a personal computer (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 study illustrates that this technology also can produce the amount of FDG required for human studies.

"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,” stated Dr. Hsian-Rong Tseng, assistant professor of molecular and medical pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA.

The objective is to integrate the new chips into a small control device operated by a PC that will be commercially produced, then to deliver chips to users so they can produce whatever molecules they choose for molecular imaging with PET. These chips will be helping technology to drive growth in the number and diversity of imaging molecules and applications of PET in biology and pharmaceutical research and in the care of patients.





Related Links:
Siemens Medical Solutions
Fluidigm