Combined effort: Spectroscopic cancer clues under the microscope

Biomedical engineering

A combination of atomic force microscopy (AFM) and nuclear magnetic resonance (NMR) spectroscopy could provide oncologists and cancer researchers with a new way to probe how cancer cells spread in the body through metastasis as well as other disease-related processes.

In work funded by Purdue University's Showalter Trust Fund and the National Institutes of Health, biomedical engineer Corey Neu and colleagues have found a way to simultaneously study the mechanical and biochemical behaviour of cells. They suggest that the work could provide new insights into disease processes. "Let's say you have a large population of cells," explains Neu. "Just one of them might metastasize or proliferate, forming a cancerous tumour. We need to understand what it is that gives rise to that one bad cell."

Technical combination

Cancer is a broad group of various diseases, rather than a single disease. However, all cancers, by definition involved unregulated cell replication whether that is bowel, breast or cancers of the blood. Malignant tumours, or growths, are common in many cancers, but are often treatable. Less commonly treatable are cancers that spread from the primary site to other tissues in the body either via the bloodstream or lymphatic system in a process known as metastasis. Understanding how metastases form and progress will be important to diagnosing and treating such forms of cancer.

The team's combined technique might allow researchers to investigate the inner workings of errant cells and so unravel the physical and biochemical responses it makes to its environment that lead to metastases.

A prototype of the technique in action has been demonstrated by obtaining the proton NMR spectra of a deionized water sample and details are reports in the journal Applied Physics Letters. Neu worked alongside, Charilaos Mousoulis, Teimour Maleki and Babak Ziaie. "You could detect many different types of chemical elements, but in this case hydrogen is nice to detect because it's abundant," Neu explains. "You could detect carbon, nitrogen and other elements to get more detailed information about specific biochemistry inside a cell."

Spreading cancer clues

AFM uses a tiny vibrating probe, the cantilever, to obtain information about materials and surfaces at the nano scale, such as individual molecules, cell membranes and other biological entities. However, AFM alone does not provide detailed molecular information, so the team fabricated a planar, metal microcoil on their AFM cantilever, which allows them to acquire NMR signals (at 500 MHz) and so probe the protons in a volume of just 19.4 picolitres. The technique should thus allow them to combine AFM's ability to carry out topographical profiling with the biochemical profile afforded by NMR.

The team explains that their technology has several advantages over other approaches. First, they say, it allows them to reveal heterogeneity between cells of similar phenotype. In cancer, such information could provide valuable mechanistic insights. In parallel, the NMR functionality allows them to identify and classify malignant cells. Moreover, NMR can give them chemical information at the intercellular level and AFM information about the stiffness of the cellular matrix, a property that influence proliferation and tumorigenesis, they say.

"In the long term, it is expected to facilitate the understanding of combined biophysical (e.g. mechanical stiffness) and biochemical (e.g. metabolic) processes within single cells to provide fundamental biomedical information, and insight for the development of therapies," the team says. The researchers also add that studying cells in "microfluidic chambers" might next allow them to test how those cells respond to specific drugs and environmental changes.

"We are currently fabricating a new integrated AFM/NMR system in our laboratory, with an intent to generate combined biophysical and biochemical profiles from clinical samples for a variety of diseases, including osteoarthritis and breast cancer," Neu told SpectroscopyNOW.