Dec 2, 2008
Airbrushed nanotubes detect cancer cells
Scientists in the US have developed a single nanotube field effect array that can detect live, intact breast cancer cells with single-cell selectivity in a drop of fresh human blood. The nanotubes are airbrushed onto a 1 cm × 1 cm chip, which can be configured to provide multiple cell recognition and could pave the way for fast-acting, low-cost hand-held oncometers.
To find out more, nanotechweb.org caught up with Balaji Panchapakesan, now based at the University of Louisville, who helped to design the device together with Ning Shao from the University of Delaware and Eric Wickstrom of Thomas Jefferson University.
In simple terms, how does the array detect the presence of a cancer cell?
Our biosensor works on the principle of the change in free energy due to receptor–antibody interaction. This change in free energy produces a stress on the surface of the nanotube that modifies the electron transport properties, which is monitored by our set-up. The change in free energy is higher for a specific receptor–antibody interaction. Non-specific antibody receptor interactions produce a lower change in free energy. This is what we see in our electronic signals. The change in conductivity is higher for specific ligand–receptor interactions compared with non-specific interactions. Therefore, the electronic signals are highly specific to a certain ligand–receptor pair. This has never been shown in the past.
One of the most important families of receptors that is being increasingly used for molecular targeting is the IGF1R and Her2 receptor. IGF1R is implicated in a wide variety of cancer types including breast, prostate, lung and pancreas cancer, and IGF1R signaling is crucial for the survival of malignant cells. Monitoring IGF1R proteins in blood can be one of the first steps in the screening and assessment of cancer. In this work, we functionalized the surface of the nanotube to be specific to IGF1R. If these receptors are found in blood or cells, the interaction of the antibody with the IGF1R produces a stress on the surface of the nanotube, which changes its electronic conductivity. Past reports have used DNA, peptides and other proteins. We have used antibodies that are highly specific to tumour cells.
Why did you decide to use nanotubes as opposed to other nanostructures such as nanowires?
Most of the nanowire devices that were reported in the past are quite easy to fabricate compared with nanotube transistors. However, nanotubes can undergo changes in electron transport properties under strain, which is useful when it comes to obtaining unique signatures. The hollow nature of the nanotube means that most of its atoms are surface atoms. Therefore, when there is a change in energy on the surface of the nanotube due to the presence of a biomolecule, the structure will respond to the molecule by changing the position of its carbon atoms, which are unique. Hence, we can create molecular fingerprints for different molecules that are of interest in screening for autoimmune disease.
What are the key advantages of your technique compared with other detection methods?
Techniques for multiplexed analysis of extracted proteins for disease monitoring can be divided into four different categories: (1) time-of-flight mass spectroscopy; (2) radioactive and fluorescent reporting of antigen-antibody binding; (3) electrophoretic separation and antigen–antibody binding; and (4) detection of changes in surface mechanical and electrical properties due to antigen–antibody binding. Although they all have their individual strengths, none of these techniques can directly detect circulating cancer cells that over-express characteristic surface receptors. The cantilever bioassay for PSA takes almost 3 hours for a single assay and cannot be adopted by portable devices.
The silicon nanowires that have shown promise still need to be modified before it can become amenable as they cannot do the assay directly on cells. Hence protein extraction steps are necessary. Here, we have shown that by just using a drop of blood you can determine whether there is any proteins that might be representative of those surface markers found in cancer cells without labelling. Different techniques have their own advantages in different situations. But all are doing one thing with a common goal to detect cancer proteins at an early stage.
The researchers presented their work in Nanotechnology.
About the author
James Tyrrell is editor of nanotechweb.org.