Biochips contain grids of small wells or "dots"

A Biochip That Can Test for Several Diseases—€”at Once

In healthcare, time means everything. Two months' delay in diagnosis can mean the difference between life and death to a cancer victim. Emergency rooms are crowded with people suffering from infections in desperate need of a quick diagnosis.

Researchers working at Argonne National Laboratory have developed a new technology, the biochip, which could help save lives by testing patients for multiple diseases at the same time—€”in some cases, testing for cancers before any symptoms develop.

The biochip consists of a one centimeter by one centimeter array that comprises anywhere between several dozen and several hundred "dots," or small drops. Each of these drops contains a unique protein, antibody or nucleic acid that will attach to a particular DNA sequence or antigen, such as Influenza A or the Streptococcus bacterium responsible for strep throat.

"Say someone shows up at the hospital and they're sick with an upper respiratory infection," said Argonne biologist Daniel Schabacker. "First thing a doctor is going to want to know is whether the infection is viral or bacterial; this is especially true in pediatrics. And ideally, they'd really like to have a single test that they can run very rapidly that will identify exactly which disease you have from a dozen top targets."

The biochip technology has shown tremendous promise in tests conducted at a number of labs and hospitals around the country, Schabacker said, and as a result four private companies have licensed the chips' core technology from Argonne. One of these companies, Akonni Biosystems of Frederick, Md., has produced dozens of assays under the TruArray—„ brand name.

The Akonni TruArray—„ rapidly screens a sample for hundreds of disease markers at one time by using hundreds of molecular biosensors in a microarray the size of a fingernail. It can screen a blood, saliva or urine sample for multiple infectious diseases associated with upper respiratory, intestinal or STD infections and determine if an infectious disease is resistant to antibiotics, or simply tell if an infection is viral or bacterial. It can also be used to identify an individual's susceptibility to an adverse drug reaction—€”invaluable when a patient is unconscious or unable to give a full medical history.

The development of products like TruArray will soon revolutionize doctors' ability to diagnose a number of diseases, Schabacker said. For example, while existing rapid strep tests performed by many pediatricians take only a few minutes to process, they yield so many false negatives doctors routinely send out the samples for subsequent rounds of more thorough, time-consuming and expensive analysis.

Though the analysis of a sample on a biochip can take 30 minutes, scientists can have much more confidence in the accuracy of the diagnosis, according to Schabacker. "Biochips give us the ability to run a test that allows your doctor to figure out exactly what you're suffering from during the time that you're in his or her office," he said.

The chips might also be used in more dire circumstances, such as when a patient presents with a potentially deadly and contagious infection. By adding a few more drops to the chip's array, Schabacker claimed, lab technicians could test for a whole slate of biotoxins and diseases such as the plague or smallpox.

Drug-resistant tuberculosis and the often-deadly Methicillin-resistant Staphyloccus aureus (MRSA) can be quickly diagnosed with biochips such as the Akonni TruArray assay, according to Akonni's president and CEO Charles Daitch.

The most important thing with these types of infections is that you have to be right and get the answer quickly," Schabacker said. "Some of the tests out there, though marginally quicker than ours, are so inaccurate they're almost useless. Especially when you're talking about anthrax or plague you have to be confident in your diagnosis or else you risk causing a panic."

Daitch said the technology might reduce costs and could change the way doctors diagnose illnesses.

"The unique advantage offered by the TruArray platform lies in the fact that we can screen a single sample for multiple viral and bacterial infections at the same time," Daitch said. "Soon doctors will no longer need to order as many expensive and time-consuming tests, and can instead obtain accurate diagnoses that will enable them to quickly provide their patients with targeted treatment strategies."

Another private company has licensed the technology to specialize in the early diagnosis of several types of cancer. Epogen of Darien is creating biomarkers that look for antibodies produced as a result of early tumors.

A tumor, even in its earliest asymptomatic phases, can slough off proteins that find their way into a patient's circulatory system. These proteins trigger the immune system to kick into gear, producing antibodies that regulate which proteins belong and which do not.

"Antibodies are the guardians of what goes on in the body," said Tim Barder, president of Eprogen, Inc. "If a cancer cell produces aberrant proteins, then it's very likely that the patient will have an antibody profile that differs from that of a healthy person. You can look for similarities and differences in autoantibody profiles to look for clues and markers that provide early indicators of disease."

By using cancer patients' own auto-antibodies as a diagnostic tool, doctors could potentially tailor treatments based on their personal autoantibody profile. "This technology is really designed to take advantage of the information contained within the patient's own biology," Barder said. "What makes this technique unique is that scientists can use the actual expression of the patient's disease as a means of obtaining new and better diagnostic information that doctors could use to understand and fight cancer better.

"We're starting to see a way of developing tests and therapies for cancer by bringing the bedside to the laboratory, rather than the other way around," he said.

Jared Sagoff is a science writer at Argonne National Laboratory.