(M2M comment- Dr. Aaron Wheeler at the Canadian Cancer Society Innovative Research in Cancer Event, Sept. 23, 2009, showed a similar device he is developing to detect Prostate Cancer.)

Joseph Hall    HEALTH REPORTER           TORONTO STAR

Aaron Wheeler holds a petri dish bearing a lump of breast tissue that resembles, in size and appearance, a piece of chewed gum.

In his right, the University of Toronto chemist holds a microchip array, about the size of a credit card, bearing a drop of red liquid about a thousand times smaller than the glob of flesh. The drop represents the minute amount of cells that Wheeler’s tiny board needs to accurately gauge estrogen levels in a woman’s breast tissue.

The invention holds out the promise in the near future of pocket-sized detectors that could help diagnose and monitor breast cancer, which requires high levels of the female hormone to thrive.

It also earned Wheeler’s U of T team the inaugural front cover of a major scientific journal.

“This is the size of tissue that you would normally need to take out to (determine) estrogen levels,” says Wheeler, holding out the petri dish. “Obviously we can’t routinely be cutting pieces like this out of women’s breasts.”

Wheeler’s work appeared Wednesday on the cover of the first issue of Science Translational Medicine, based in Washington, D.C.

An offshoot of the prestigious weekly Science, the journal spotlights work progressing out of the laboratory into hospitals.

Wheeler freely admits the prominent coverage could help attract investors for his device, which he hopes to couple with emerging microchip analyzer technology to create a pocket-sized screener for breast cancer.

Women with such cancers have much higher levels of estrogen in the surrounding tissue. And there is growing evidence the hormone is greatly elevated in women at risk of developing breast cancer.

Currently, however, these telltale estrogen levels can only be determined by cutting fingertip-sized pieces of tissue out of the breast for lab analysis. Because they’re so painful and disfiguring, however, such tests are rarely done.

Wheeler says his “lab on a chip” technology would require only a fraction of the sample cells, obtained with a simple needle prick.

The device works by using electrical charges to “dance” droplets of liquids on a precise route over the surface of the microchip circuitry.

One solvent droplet is sent over a dried sample of tissue to open up the cellular walls. Another is then sent in to extract the intercellular contents that have been exposed.

That millimetre-wide drop is then directed through another liquid reservoir, which removes all the other cellular materials, leaving only the purified estrogen to carry on.

“Then we pull (the droplet) out and do the analysis,” Wheeler says. This process is currently done by lab technicians and can take several days to produce results.

Wheeler says his results would be available in minutes. Experiments on the tissues of two women with breast cancer have shown that this process extracts enough estrogen to give doctors accurate levels, says Dr. Noha Mousa, the lead study author.

By combining the device with a microchip estrogen detector, the entire process could be exported from lab settings to doctors’ offices.

The pocket-sized devices could be used both to monitor women being treated for breast cancer and as a screening tool, says Mousa.

Microfluidics chips allow scientists to study circulating cancer cells and determine their vulnerabilities.

By Emily Singer         from   MIT Technology Review

In a new clinical trial for prostate cancer, scientists will capture rare tumor cells circulating in patients’ blood, analyze them using a specialized microchip, and use the results to try to predict how well the patient will respond to a drug. The trial reflects a new phase of personalized medicine for cancer, enabled by microfluidics technologies that can isolate scarce cancer cells and detect very small changes in gene expression.
Physicians ultimately hope these chips can become a routine part of clinical care for cancer. “We need to be able to profile the tumor at the time we are considering treatment,” says Howard Scher, chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center, where the trial will take place.

Cell circuits: Scientists will use the Fluidigm chip (above) to analyze tumor cells isolated from the blood of patients with prostate cancer. The array comprises a matrix of integrated channels and valves (center) housed in an input frame and can run 9,216 parallel reactions.
Credit: Fluidigm

The study will focus on men with a difficult to treat form of prostate cancer that has failed to respond to other therapies. Changes in gene expression might help determine whether a specific drug will be effective–for example, if a patient has high levels of a receptor for androgen hormones, a drug that inhibits signaling of that receptor is more likely to work well. “We want to know why they don’t respond to therapy and what therapies would be best for them,” says Martin Fleisher, chairman of the Department of Clinical Laboratories at Sloan. “We collect tumor cells from blood, and do a gene analysis to find out what genes are overexpressed and whether or not they would be candidates for certain types of targeted therapies that would beat down their cancer.”

The effectiveness of different cancer drugs can vary based on the molecular characteristics of the cancer, such as the presence of a certain hormone or genetic mutation. Physicians already do some molecular analysis of cancer tissue to select the best drug for a patient. Herceptin, for example, is used to treat breast cancer in women with a particular protein in their tumors. And lung cancer patients with a mutation in the gene for the epidermal growth factor receptor are more likely to respond to a drug called Iressa than patients without it. But these treatments are chosen based on analysis from tumor biopsies, which isn’t always possible.

Analyzing tumor cells in blood presents two major challenges. Tumor cells are found at very low concentrations in the blood–about one in ten million cells–making it difficult to isolate them. And the small numbers of cells must be analyzed in very low volumes. In the last year, Sloan scientists and others have developed ways to capture these cells using antibodies that detect a molecular marker present only in cancer cells.

In the new Sloan study, scientists face an even more challenging problem–they must detect differences in gene expression, rather than a specific genetic mutation, such as the mutation linked to Iressa responsiveness in lung cancer. Scher and collaborators will use a microfluidics chip made by Fluidigm, a South San Francisco, CA- based company . DNA from each cell is filtered into one of 96 tiny channels on one side of the chip, while reagents flow in from 96 channels on the other side. A precise plumbing system then combines the molecules in different combinations, generating about 9,000 simultaneous reactions. Each reaction takes a volume of just nanoliters–about the size of a period–rather than the microliter volume typical of most commercial fluidics devices. The chip, which costs about $300, “can detect differences in gene expression that are as subtle as twofold with very good accuracy,” says Gajus Worthington, Fluidigm’s president, CEO, and co-founder.

Researchers plan to analyze levels of about 30 genes in each patient, including genes involved in production of testosterone and in cell signaling. Expression of these genes has been shown in animal models to predict how well a tumor will respond to a drug called dasatinib, which is approved for treatment of chronic myelogenous leukemia and in late stage clinical trials for prostate cancer.

The microfluidics technology could also be used to examine other properties of tumor cells. Scientists might look for changes in gene expression that suggest a cancer has metastasized, or whether a tumor has evolved specific mutations that make it resistant to specific drugs.

by Megan Ogilvie & Joseph Hall
Toronto Star

Toronto researchers have developed a portable device they say will accurately diagnose prostate cancer in 30 minutes.

The microchip technology, created by a pair of University of Toronto scientists, will be able to determine the severity of the tumours through a simple urine sample and produce quick diagnosis with no need for painful biopsies.

Now heading into the engineering stage, a BlackBerry-sized device should be available for doctors’ use within two to three years and eventually could be tuned to detect a broad range of cancers and infectious ailments, the researchers say.

“The goal would be to produce a result … while you’re sitting in the waiting room,” said engineering professor Ted Sargent, who holds the U of T’s Canada Research Chair in Nanotechnology.

A paper on the work was published yesterday in the journal Nature Nanotechnology.

The device uses a fingertip-sized microchip – fitted with microscopic meshing – programmed to detect DNA sequences and proteins uniquely produced by specific cancers or pathogens.

These “biomarkers” would be drawn from urine or blood samples.

“We simply put a sample on the chip and we have a nice small chip reader that then analyses it and tells you what markers are in the sample,” said Shana Kelley, a U of T pharmacology professor and study co-author.

Detected markers can tell you not only which kind of cancer is present, but also the stage and severity the tumour has attained.

“That’s very important to be able to do that because cancers are actually a bunch of different diseases with different levels of aggressiveness,” said Kelley. “Particularly in prostate cancer, there are very non-aggressive forms … that you simply want to leave alone.”

Kelley said the technology could herald an age of surgery-free diagnosis for cancer patients. “The real drive is toward non-invasive diagnostics so we can just screen people without having to take parts of their organs in order to do it,” she said.

Dr. Tom Hudson, scientific director of the Ontario Institute for Cancer Research, said the study is “proof of principle” that it is possible to have a quick, affordable technology that can test for different cancer biomarkers at once.

“This is a critical step,” he said. “They have shown you can detect this gene mutation (for prostate cancer). And if you extrapolate that you can do it for one gene, you could probably do it for 100 or 1,000.”

Scientists are working hard to identify biomarkers for specific cancers and test those markers’ usefulness in diagnosing cancer in patients. Some 1,000 biomarkers have been found, but Hudson said only nine of those have been validated so far in the clinic.

The other challenge is to find a way to test for many different biomarkers at once and develop a cost-effective technology to do it.

Hudson cautioned the device is still a long way off from being a staple in doctor’s offices.

“How we make these (biomarker) tests happen in the clinic or in the clinical lab really needed some advances in technology. And Kelley and Sargent have done all the proof of principles here for a technology that’s going to work.”

For the initial work, Sargent and Kelley looked at prostate cancer, which has a set of signature biomarkers, shown in many studies to accurately portray the presence and severity of that disease.

The pair showed the chips were well able to pick up these makers in the minuscule concentrations typically found in the urine of prostate cancer patients.

But even now, Kelley said, they are shifting the technology’s sights to other cancers and ailments.

“We’ve already done a little bit of work with head and neck cancer,” Kelley said. “But really any cancer where there is an established molecular profile, we should be able to pick up using this device.”

Sargent said he envisions the devices being a commonplace tool in doctors’ offices around the world, along with a binder full of chips for different cancers and diseases.

“Say you were looking for H1N1 (influenza) or some dangerous infectious agent, there could be chips specific to those,” he said. “You would just insert the proper one.