New technology could replace time-intensive urine specimens

For the millions of people who suffer from urinary tract infections each year and the doctors who treat them, a promising new biosensor technology has been developed that may replace antiquated testing methods and save precious health care dollars.

In a recent clinical study conducted by the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System, researchers used a biosensor developed by corporate partner GeneFluidics to identify correctly the infection-causing gram negative bacteria species in 98 percent of the tested clinical urinary tract infection urine samples. These results represent the first ever species-specific detection of bacteria in human clinical fluid samples using a microfabricated electrochemical sensor array.

Of equal significance, the new test provided results in 45 minutes, compared to two days with conventional methods.

The research, reported in the February 2006 issue of the peer-reviewed Journal of Clinical Microbiology, investigated a new technology to solve an old problem: the diagnosis of urinary tract infections -- the second most common bacterial infection -- in a clinically relevant timeframe.

In current laboratory practice, contaminating pathogens in urine specimens are grown in culture dishes until they can be visually identified. The major drawback of this century-old technique is the two-day time lag between specimen collection and bacteria identification. As a result, physicians must decide whether to prescribe antibiotic therapy and, if so, which type of bacteria to treat -- all without knowing the cause of the infection, if any. In contrast, the new biosensor technology would allow physicians to prescribe targeted treatment without the wait.

"Our research also showed that GeneFluidics' biosensor avoided problems inherent in alternative molecular approaches, such as PCR, that require the repeated copying of bacterial DNA or RNA prior to testing. We found that these amplification methods do not provide reproducible results," said lead author Dr. Joseph C. Liao, clinical instructor of urology at the David Geffen School of Medicine at UCLA.

The clinical study was performed at the VA Greater Los Angeles Healthcare System in the laboratory of Dr. David Haake, VA staff physician and professor of medicine at UCLA. Researchers studied samples received by the UCLA Clinical Microbiology Laboratory.

Individual sensors on GeneFluidics' 16-sensor chips were coated with UCLA-designed species-specific genetic probes. Clinical urine samples were directly applied to the chips and the electrochemical signal subsequently measured by GeneFluidics' multi-channel reader instrument. The urinary tract infection pathogens were identified by examining which signals on the sensor chip were elevated. The entire experiment from sample collection to result read-out took only 45 minutes.

The potential for rapid bacterial detection was discovered in the laboratory of Dr. Edward McCabe, chair of pediatrics at the Mattel Children's Hospital at UCLA and an adviser to GeneFluidics. McCabe's group demonstrated that probes could bind to species-specific bacterial sequences within minutes, rather than hours. These exciting results were translated to the biosensor protocol, leading to the development of the biosensor for rapid identification of bacteria in urine from patients with urinary tract infections.

"Results were impressive for this initial 78-sample clinical study," said Dr. Bernard Churchill, chief of pediatric urology at the Clark-Morrison Children's Urological Center at UCLA and principal investigator. "By coupling UCLA's robust probes with GeneFluidics' ultra sensitive biosensor system, we were able to identify urinary tract infection pathogens in a time frame that would enable physicians to make dramatically superior clinical decisions."

Ongoing work at UCLA and the VA Medical Center is focused on developing even better detection methods to bring the urinary tract infection biosensor chip from "bench to bedside." At GeneFluidics, engineers are integrating the biosensors into microfluidic cartridges and building a new instrument for faster and completely automated experimentation. The team anticipates the rapid test could become available in the next two to three years.

"There is considerable interest in decreasing overall health care costs by providing smarter medicine," added Dr. Vincent Gau, chief executive officer of GeneFluidics. "When laboratory-quality testing can be rapidly performed by anyone, anywhere, and the results made available in 'real-time,' we will see tremendous improvement in patient care. This joint project with UCLA may spearhead that shift."

Urinary tract infection is the most common urological disease in the United States and the most common bacterial infection of any organ system. Urinary tract infection is a major cause of patient death and health care expenditure for all age groups, accounting for more than 7 million office visits and more than 1 million hospital admissions per year. In the hospital, catheter associated urinary tract infection accounts for 40 percent of all in-hospital acquired infections -- more than 1 million cases each year. The total cost of urinary tract infections to the United States health care system in 2000 was approximately 3.5 billion dollars.

The collaboration between UCLA, VA and GeneFluidics began in 2001, thanks to initial funding from Frank W. Clark Jr., and the Wendy and Ken Ruby Fund for Excellence in Pediatric Urology Research.

Subsequently, the work has been supported by a $5.6 million Bioengineering Research Partnership grant from the National Institute of Biomedical Imaging and Bioengineering.