Sticking It to Lung Cancer


A polymer-nanofiber NanoVelcro chip. Image: UCLA

Lung cancer is by far the most lethal form of cancer, and lung cancer research is fraught with sticky scientific problems. Catching the disease early and finding the right treatment are the stickiest. But a new nanochip with a Velcro-like grip is grabbing the attention of lung cancer oncologists eager for a diagnostic breakthrough that sticks.

Developed at the California NanoSystems Institute at the University of California Los Angeles, the NanoVelcro Chip is a blood testing device featuring a silicon nanowire substrate that selectively screens out high-purity early traces of cancer. Using about 2 mL of blood as opposed to invasive surgical biopsies or complex imaging methods, the chip has implications in a number of cancers. Recent improvements have shown potential in the care of advanced lung cancer, where any life-extending progress is cause for celebration.

The nanowire substrate gets its Velcro-like properties from a coating of special cancer-attracting antibodies. Traces of tumor DNA suspended in blood sample stick with hook-and-loop tenacity to the substrate, where they are held for subsequent analysis.

The device is one of a number of emerging approaches to noninvasive cancer detection and monitoring based on the analysis of circulating tumor cells (CTCs) in blood. These cellular fragments from a growing tumor carry copies of its mutated genetic material through the bloodstream to new parts of the body, where they can corrupt healthy cells. By catching and analyzing CTCs, researchers are learning to create detailed, patient-specific molecular profiles of a tumor its most attractive targets for treatment. Several new large-scale studies of these so-called liquid biopsies have recently strengthened many doctors’ confidence in using them in patient care. CTCs have potential in early cancer detection, but a nearer-term payoff is likely as a target for molecular characterization and monitoring of cancer cells in response to treatment.

NanoVelcro was developed by an international team of scientists and engineers from UCLA and Japan’s Riken Advanced Science Institute. UCLA team leader Hsian-Rong Tseng says the material catches CTCs with killer precision but handles them with kid gloves to ensure they are not physically altered before they are assayed.

Configuration of the polymer-nanofiber NanoVelcro Chip. Image: UCLA

Hot-Blooded Biopsy

Once captured, CTCs must be extracted from the chip without harming them to ensure accurate analysis. The original – and still standard – method for removing CTCs from the NanoVelcro substrate is laser capture microdissection (LCM). Although effective, LCM is time-consuming and requires specialized equipment. A focus of Tseng’s ongoing work is to simplify the process as much as possible while retaining the vital integrity of the CTCs. One answer, it seems, was a close as the nearest Starbucks.

By endowing the NanoVelcro Chip with temperature-responsive polymer “brushes,” Tseng says, the group has achieved good CTC capture-and-release efficiency simply by manipulating the temperature of the blood sample – the way a skilled barista can adjust the properties of a drink to customer specification. 

“With our new system, we can control the blood’s temperature the way coffee houses would with an espresso machine — to capture and then release the cancer cells in great purity,” he says.

At 37 degrees Celsius, blood-borne CTCs adhere to the thermoresponsive brush material and stay there. To introduce the cells into downstream analytical instrument or gene sequencer, the researcher simply lowers the temperature of the blood sample to 4 degrees C and they are released in a state of high purity.

Tseng says the technology could provide a cost-effective and fast alternative to the standard LCM approach in the care of patients for whom time is of the essence. By combining the NanoVelcro capture approach with mutational analysis, he said, the technology has successfully monitored the disease’s evolution at the molecular level in real patients.

Catching the Top Killer

Lung cancer claims some 160,000 lives each year in the United States and 10 times more on a global scale. Its lethality rate that far surpasses that of breast, prostate, and colon cancer combined. Stealth is its ultimate weapon. The telltale symptoms rarely appear until a tumor is advanced, so the disease is almost always diagnosed after it’s already beyond treatment. Among patients diagnosed with stage 4 lung cancers, 96% will die within five years.

However, new targeted drugs like Tarceva have been effective against lung cancers caused by specific genetic mutations. Another cause excitement is a new generation of immunotherapies like the just-approved Opdivo. In many cancers, precision combinations of molecularly targeted and immunotherapeutic drugs like these are fueling new optimism. With the added diagnostic and monitoring support of techniques such as NanoVelcro, doctors and patients have a new source of hope to hang on to.

Michael MacRae is an independent writer.

Learn about the latest trends in medical diagnostics at ASME’s Global Congress on NanoEngineering for Medicine and Biology.

With our new system, we can control the blood’s temperature the way coffee houses would with an espresso machine.

Hsian-Rong Tseng, California NanoSystems Institute, UCLA


August 2015

by Michael MacRae,