New 'lab-on-a-chip' could change cancer diagnosis

8 October 2014

Promising new biomarkers called "exosomes" have been the focus of much research in recent years to diagnose cancer, along with other diseases. These exosomes could lead to less invasive and earlier detection of cancer, which could significantly increase survival rates. 

“Exosomes are minuscule membrane vesicles - or sacs - released from most, if not all, cell types, including cancer cells,” said Dr Yong Zeng, assistant professor of chemistry at the University of Kansas. 

At first, it was assumed that these biomarkers were were 'cell dust' containing unwanted contents, but in the past decade researchers have found that exosomes play an important role for many biological functions. Studies identified that they encapsulate and deliver molecular messages from donor cells to affect the functions of nearby or distant cells. 

However, exosomes are so small that isolating them for testing is extremely challenging, meaning that a tedious and inefficient process - multiple-step ultracentrifugation - is needed and takes up a lot of lab time.

“There aren’t many technologies out there that are suitable for efficient isolation and sensitive molecular profiling of exosomes,” said Dr Zeng.  “First, current exosome isolation protocols are time-consuming and difficult to standardise. Second, conventional downstream analyses on collected exosomes are slow and require large samples, which is a key setback in clinical development of exosomal biomarkers.”

However, now Dr Zeng and his colleagues from the University of Kansas (KU) Medical Center and KU Cancer Center have published a breakthrough paper in the Royal Society of Chemistry journal. The report details their creation of a miniaturised biomedical testing device for exosomes. 

Named the "lab-on-a-chip” device, it is able to deliver faster result times, reduced costs, minimal sample demands and an increased sensitivity with results, compared to the conventional bench-top instruments currently used to examine the tiny biomarkers.

Dr Zeng said the device is able to "shrink" the pipettes, test tubes and analysis instruments used in modern labs to a "microchip-sized wafer". He added that the prototype device consists of a widely used silicone rubber called polydimethylsiloxane. 

Also referred to as ‘microfluidics’ technology, it allows precise manipulation of tiny amounts of fluid to carry out multiple laboratory functions, such as sample purification, running of chemical and biological reactions, and analytical measurement, according to the expert.

The team developed the lab-on-a-chip to detect lung cancer in the early stages, which is currently diagnosed through an invasive biopsy. This can usually only detect tumours that are large than three centimeters, but the new device could identify the disease much earlier with a single drop of blood from the patient.

“Most lung cancers are first diagnosed based on symptoms, which indicate that the normal lung functions have been already damaged,” Dr Zeng said. “Tumour biopsy is often impossible for early cancer diagnosis as the developing tumour is too small to see by the current imaging tools."

The chip uses magnetic beads to pull down the exosomes in plasma samples, while the surface is chemically modified with an antibody to help isolate the biomarkers from other "interfering species present in plasma".

The plasma, with these magnetic beads, then flows through the microchannels on the chip where they can be collected using a magnet to extract "circulating exosomes" from the plasma, explained Dr Zeng.

Posted by Philip Briggs​

 

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