March 14, 2006
Blood Protein Test Orders Of Magnitude More Sensitive

Want an example of yet another orders of magnitude improvement in what bioscientists and biotechnologists can do? Blood tests will be able to detect diseases at much earlier stages when the FACTT assay reaches the market.

(Philadelphia, PA) - Researchers at the University of Pennsylvania School of Medicine have developed a paradigm-shifting method for detecting small amounts of proteins in the blood. Applications of this method will make discerning low-abundance molecules associated with cancers (such as breast cancer), Alzheimer's disease, prion diseases, and possibly psychiatric diseases relatively easy and more accurate compared with the current methodology, including the widely used ELISA (enzyme-linked immunoadsorbent assay).

ELISA is a common immune-system-based assay that uses enzymes linked to an antibody or antigen as a marker for picking out specific proteins. For example, it is used as a diagnostic test to determine exposure to infectious agents, such as HIV, by identifying antibodies present in a blood sample.

The sensitivity of detecting molecules by the new method, called FACTT, short for Florescent Amplification Catalyzed by T7-polymerase Technique, is five orders of magnitude (100,000 times) greater than that of ELISA, the Penn researchers found.

Senior author Mark I. Greene MD, PhD, the John Eckman Professor of Medical Science, Hongtao Zhang, PhD research specialist; Xin Cheng, PhD, research investigator, and Mark Richter, a research technician in Greene's lab, report their findings in the advanced online publication of Nature Medicine.

"The current ELISA tests can only detect proteins when they are in high abundance," says Zhang. "But the problem is that many of the functional proteins - those that have a role in determining your health - exist in very low amounts until diseases are apparent and cannot be detected or measured at early stages of medical pathology. It was important to develop a technique that can detect these rare molecules to detect abnormalities at an early stage."

One problem that'll arise as a result of more sensitive blood and saliva assays is finding very early stage cancers. Okay, you'll know you have cancer. But it is incredibly small and your body is big. How to find it? As things stand now in spite of advanced CAT scanners and MRI machines surgeons sometimes have to cut into people to poke around to find something oncologists can't localize even at an advanced state of illness.

Imagine a cancer about the size of a needle tip. You have lots of little cancers in your body that are stuck at a small size because they haven't mutated the ability to grow blood vessels (they do not yet secrete angiogenesis factors). How to find just the right cancer to remove that has just crossed that threshold? Seems hard to me.

Share |      Randall Parker, 2006 March 14 10:41 PM  Biotech Assay Tools

Stephen Gordon said at March 14, 2006 11:36 PM:

How to find it?

Dr. James Baker is working on a solution.

He's working on nanoparticles called dendrimers that can make a cancer light up on an MRI. Dendrimers could even treat the cancer at the same time.

Ned said at March 16, 2006 8:54 AM:

The major use of this technology, as with most cancer biomarkers, would be to detect recurrence, not for initial diagnosis. A good example is serum PSA, the prostate marker. Although this is currently used to "screen" for prostate cancer (largely because there is nothing better), it is a crude and insensitive tool. Yes, many prostate cancers cause elevation of PSA, but so do other common conditions, including inflammation and benign enlargement of the gland. Even if a cancer is there, the urologist still has to find it with his needle, although ultrasound is a big help here. However, in a patient who has had a prostatectomy for cancer, PSA should disappear entirely, so that any detectable level should indicate cancer recurrence. With rare exceptions, cancer biomarkers are of little use in initial diagnosis or screening for cancer. Consider a new biomarker that is 100% sensitive and 100% specific for breast cancer. Suppose this protein were detected at an extremely low level in a woman. What should she do? Careful physical and radiologic examination of her breasts would not reveal any abnormality because the lesion would be so small. Even if she opted for bilateral mastectomies, how could the pathologist ever find the cancer?

AMac said at March 17, 2006 2:51 PM:


You make good points, but your example of a 100% sensitive, 100% accurate ("100% AUC") breast cancer marker isn't apt. If such a marker existed, many women faced with the choice you present would readily choose a double mastectomy. This is analogous in some ways to the serum level of PSA, post-prostatectomy.

Finding that 100% marker is the hard part...

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