New imaging technology could reveal cellular secrets

April 25, 2013 − by wpengine − in Archived − No Comments

April 25, 2013

cancer-cell metastasis

This image illustrates the
concept for a new type of technology that combines two biological imaging
methods – atomic force microscopy and nuclear magnetic resonance – to create a
new way to study cancer-cell metastasis and other disease-related processes. (Purdue
University image/ Xin Xu)

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WEST LAFAYETTE, Ind. – Researchers have married two
biological imaging technologies, creating a new way to learn how good cells go
bad.

“Let’s say you have a large population of
cells,” said Corey Neu, an assistant professor in Purdue University’s
Weldon School of Biomedical Engineering. “Just one of them might
metastasize or proliferate, forming a cancerous tumor. We need to understand
what it is that gives rise to that one bad cell.”

Such an advance makes it possible to simultaneously study
the mechanical and biochemical behavior of cells, which could provide new
insights into disease processes, said biomedical engineering postdoctoral
fellow Charilaos “Harris” Mousoulis.

Being able to study a cell’s internal workings in fine
detail would likely yield insights into the physical and biochemical responses
to its environment. The technology, which combines an atomic force microscope
and nuclear magnetic resonance system, could help researchers study individual
cancer cells, for example, to uncover mechanisms leading up to cancer
metastasis for research and diagnostics.

The prototype’s capabilities were demonstrated by taking
nuclear magnetic resonance spectra of hydrogen atoms in water. Findings
represent a proof of concept of the technology and are detailed in a research
paper that appeared online April 11 in the journal Applied Physics Letters. The paper was co-authored by Mousoulis;
research scientist Teimour Maleki; Babak Ziaie, a professor of electrical and
computer engineering; and Neu.

“You could detect many different types of chemical
elements, but in this case hydrogen is nice to detect because it’s
abundant,” Neu said. “You could detect carbon, nitrogen and other
elements to get more detailed information about specific biochemistry inside a
cell.”

An atomic force microscope (AFM) uses a tiny vibrating
probe called a cantilever to yield information about materials and surfaces on
the scale of nanometers, or billionths of a meter. Because the instrument
enables scientists to “see” objects far smaller than possible using light
microscopes, it could be ideal for studying molecules, cell membranes and other
biological structures.

However, the AFM does not provide information about the
biological and chemical properties of cells. So the researchers fabricated a
metal microcoil on the AFM cantilever. An electrical current is passed though
the coil, causing it to exchange electromagnetic radiation with protons in
molecules within the cell and inducing another current in the coil, which is
detected.

The Purdue researchers perform “mechanobiology”
studies to learn how forces exerted on cells influence their behavior. In work
focusing on osteoarthritis, their research includes the study of cartilage
cells from the knee to learn how they interact with the complex matrix of
structures and biochemistry between cells.

Future research might include studying cells in
“microfluidic chambers” to test how they respond to specific drugs
and environmental changes.

A U.S. patent application has been filed for the concept.
The research has been funded by Purdue’s Showalter Trust Fund and the National
Institutes of Health.

Writer: Emil Venere, 765-494-4709, venere@purdue.edu 

Sources: Corey
Neu, 765-496-1426, cpneu@purdue.edu

Charilaos
“Harris” Mousoulis, cmousoul@purdue.edu 

Note to
Journalists
: Journalists can obtain a copy of the research paper by
contacting Emil Venere, Purdue News Service, at 765-494-4709, venere@purdue.edu


ABSTRACT

Atomic
Force Microscopy-Coupled Microcoils for Cellular-Scale Nuclear Magnetic
Resonance Spectroscopy
 

Charilaos
Mousoulis,1 Teimour Maleki,2 Babak Ziaie,1,2,3 and Corey P. Neu1,a

1
1Weldon School of Biomedical Engineering, Purdue University  

2
2Department of Electrical and Computer Engineering, Purdue University

3
Birck Nanotechnology Center, Purdue University

We present the coupling of
atomic force microscopy (AFM) and nuclear magnetic resonance (NMR) technologies
to enable topographical, mechanical and chemical profiling of biological
samples. Here, we fabricate and perform proof-of-concept testing of radiofrequency
planar microcoils on commercial AFM cantilevers. The sensitive region of the
coil was estimated to cover an approximate volume of 19.4 10 3 lm3 (19.4 pl).
Functionality of the spectroscopic module of the prototype device is
illustrated through the detection of 1H resonance in deionized water. The
acquired spectra 14 depict combined NMR capability with AFM that may ultimately
enable biophysical and biochemical studies at the single cell level. VC 2013
AIP Publishing LLC. [http://dx.doi.org/10.1063/1.4801318].






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