At present, diagnosis of lung cancer relies on an invasive biopsy that is only effective after tumors are bigger than 3 cm or even metastatic. Earlier detection would vastly improve patients’ chances of survival. Now a team of researchers is developing a “lab-on-a-chip” that promises to detect lung cancer – and possibly other deadly cancers – much earlier, using only a small drop of a patient’s blood.
In the Royal Society of Chemistry journal, Yong Zeng, assistant professor of chemistry at the University of Kansas, and colleagues report a breakthrough study describing their invention.
For some time, scientists have been excited by the idea of testing for disease biomarkers in “exosomes” – tiny vesicles or bags of molecules that cells, including cancer cells – release now and again. When they first spotted them, researchers thought exosomes were just for getting rid of cell waste, but now they know they also do other important things such as carry messages to other cells near and far.
The challenge, however, is developing a technology that is small enough to target and analyze the contents of exosomes – mostly nucleic acids and proteins – to find unique biomarkers of disease. This is because exosomes are tiny – around 30 to 150 nanometers (nm) in diameter – much smaller, for example, than red blood cells.
Current methods for separating out and testing exosomes require several steps of ultracentrifugation – a lengthy and inefficient lab procedure, as Prof. Zeng explains:
“There aren’t many technologies out there that are suitable for efficient isolation and sensitive molecular profiling of exosomes. First, current exosome isolation protocols are time-consuming and difficult to standardize. Second, conventional downstream analyses on collected exosomes are slow and require large samples, which is a key setback in clinical development of exosomal biomarkers.”
Now, using microfluid technology, he and his colleagues have developed a lab-on-a-chip that can analyze the contents of targeted exosomes and spot the early signs of deadly cancer. They have already successfully tested it on lung cancer.
The new device, which uses much smaller samples, promises to produce results faster, more cheaply, with better sensitivity compared to conventional benchtop instruments, as Prof. Zeng continues to explain:
“A lab-on-a-chip shrinks the pipettes, test tubes and analysis instruments of a modern chemistry lab onto a microchip-sized wafer.”
The technology behind the device – known as microfluidics – came out of new semiconductor electronics and has been under intensive development since the 1990s, he adds:
“Essentially, it allows precise manipulation of minuscule fluid volumes down to one trillionth of a liter or less to carry out multiple laboratory functions, such as sample purification, running of chemical and biological reactions, and analytical measurement.”
Unlike breast and colon cancer, there is no widely accepted screening tool for lung cancer, which in most cases is first diagnosed based on symptoms that normally indicate lung function is already impaired.
To diagnose lung cancer, doctors have to perform a biopsy – remove a piece of tissue from the lung and send it to a lab for molecular analysis. It is rarely possible to do this in the early stages as tumors are too small to be spotted on scans.
“In contrast, our blood-based test is minimally invasive, inexpensive, and more sensitive, thus suitable for large population screening to detect early-stage tumors,” says Prof. Zeng, adding that the technique offers a general platform for detecting exosomes from cancer cells. The team has already used the device to test for ovarian cancer, and in theory, says Prof. Zeng, it should also be applicable to other cancer types.
“Our long-term goal is to translate this technology into clinical investigation of the pathological implication of exosomes in tumor development. Such knowledge would help develop better predictive biomarkers and more efficient targeted therapy to improve the clinical outcome,” he adds.
The team has received further funding from the National Cancer Institute at the National Institutes of Health to further develop the lab-on-a-chip.
In March 2013, Medical News Today learned how another team of scientists is developing a lab-on-a-chip that is implanted under the skin to track levels of substances in the blood and transmit the results wirelessly to a smartphone or other receiving device.