Researchers from the University of Kansas Medical Centre and KU Cancer Center (KS, US) have published a paper in the journal Lab on a Chip, detailing their invention of a miniaturized biomedical testing device for exosomes. The ‘lab-on-a-chip’ device promises faster result times, reduced costs, minimal sample demands and better sensitivity when compared with the conventional instruments currently in use.
“Exosomes are minuscule membrane vesicles – or sacs – released from most, if not all, cell types, including cancer cells,” explained author Yong Zeng of the University of Kansas. “First described in the mid-’80s, they were once thought to be ‘cell dust’, or trash bags containing unwanted cellular contents. However, in the past decade scientists realized that exosomes play important roles in many biological functions through capsuling and delivering molecular messages in the form of nucleic acids and proteins from the donor cells to affect the functions of nearby or distant cells.”
Exosomes are extremely small, 30–150 nm in size, and are therefore difficult to isolate and analyze. Zeng continued: “There aren’t many technologies out there that are suitable for efficient isolation and sensitive molecular profiling of exosomes.”
The techniques currently employed can be time-consuming and difficult to standardize. Furthermore, Zheng stated: “conventional downstream analyses on collected exosomes are slow and require large samples, which is a key setback in clinical development of exosomal biomarkers.”
To combat the inadequacy of conventional techniques, Zeng and his colleagues developed a lab-on-a-chip device. According to Zeng, the device 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.”
In this case, the device has been employed for early detection of lung cancer – the greatest contributor to cancer deaths in the US today. Currently lung cancer is detected with an invasive biopsy after tumors are larger than 3 cm. Lung cancer could be detected much earlier with the lab-on-a-chip device, with only a small drop of a patient’s blood.
The prototype device is constructed using a silicone rubber termed polydimethylsiloxane and employs a technique known as ’on-chip immunoisolation’. Magnetic beads, 3 µm in diameter, are used to pull down the exosomes in plasma samples. To avoid interfering species present in the plasma, the bead surface is functionalized with an antibody that recognizes and binds with a specific target protein i.e., a protein receptor present on the exosomes membrane. The plasma containing magnetic beads then flow through microchannels on the diagnostic chip, where the beads can be readily collected using a magnet.
The technique developed by the researchers could potentially be used to detect a plethora of cancers. “Our technique provides a general platform to detecting tumor-derived exosomes for cancer diagnosis,” Zeng stated. “In theory, it should be applicable to other types of cancer. 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.”
Sources: New ‘lab-on-a-chip’ could revolutionize early diagnosis of cancer; He M, Crow J, Roth M, Zeng Y, Godwin AK. Integrated immunoisolation and protein analysis of circulating exosomes using microfluidic technology. Lab Chip. 14(19), 3773–3780, (2014).