This device uses magnetic fields to separate cells by size and shape. Credit: Hur Koser

Researchers at Yale have demonstrated a device that uses a magnetic liquid to separate blood cells based on their size and shape in just minutes.

The device applies a magnetic field to a liquid containing magnetic nanoparticles. The nanoparticles create waves that carry cells along depending on their size, shape and mechanical properties. The researchers, led by electrical engineering professor Hur Koser, hope to develop a cheap alternative to cell-sorting techniques that are time-consuming and sometimes require expensive labeling.

Liquid suspensions of magnetic particles, called ferrofluids, are already used as industrial lubricants and in loudspeakers and computer hard disks. These liquids typically contain other chemicals to keep the particles from clumping together and from coming out of the suspension. Magnetic nanoparticles are also being explored for cancer therapies and as contrast agents for magnetic resonance imaging (MRI)--both applications that require very low concentrations.

But the Yale group is the first to make a high-concentration, biocompatible ferrofluid that doesn't contain any chemicals that are harmful to cells, yet still keeps the particles afloat. "It was very tricky to find the parameters to maintain live cells," says Koser.

In experiments described this week in the Proceedings of the National Academy of Sciences, the Yale researchers made microfluidic channels lined with magnetic-field-generating electrodes. Cells were then added to a ferrofluid in the channel. When magnetic fields were applied along the device, the particles in the fluid pushed the cells along the channel, separating them by size and shape. Something similar can be accomplished using electrical fields, says Koser, but this can damage the cells. His group used the device to separate live blood cells from sickle cells and bacteria.

Koser believes the device could be especially helpful when trying to detect very rare types of blood cell, such as cancerous ones. Rapidly sorting cells using magnetic fields could improve the sensitivity of tests for these rare cells without adding any costly chemical labels. Tumor cells are squishier than healthy ones--possibly because they grow quickly and so don't form a proper internal cell skeleton--and Koser hopes that magnetic fields will also be able to separate cells based on their elasticity and other mechanical properties.

"The next step is to try this in conjunction with existing sensors to improve their sensitivity and cut down on time," says Koser.

In the video below, a magnetic field creates waves in a liquid containing magnetic nanoparticles (the nanoparticles are not visible) to separate two types of microbeads based on their size.

This image of pentacene, a molecule made up of five carbon rings, was made using an atomic-force microscope. Credit: Science/AAAS

Using an atomic-force microscope, scientists at IBM Research in Zurich have for the first time made an atomic-scale resolution image of a single molecule, the hydrocarbon pentacene.

Atomic-force microscopy works by scanning a surface with a tiny cantilever whose tip comes to a sharp nanoscale point. As it scans, the cantilever bounces up and down, and data from these movements is compiled to generate a picture of that surface. These microscopes can be used to "see" features much smaller than those visible under light microscopes, whose resolution is limited by the properties of light itself. Atomic-force microscopy literally has atom-scale resolution.

Still, until now, it hasn't been possible to use it to look with atomic resolution at single molecules. On such a scale, the electrical properties of the molecule under investigation normally interfere with the activity of the scanning tip. Researchers at IBM Research in Zurich overcame this problem by first using the microscope tip to pick up a single molecule of carbon monoxide. This drastically improved the resolution of the microscope, which the IBM scientists used to make an image of pentacene. They arrived at carbon monoxide as a contrast-enhancing addition after trying many chemicals.

The researchers hope that looking this closely at single molecules will give them a better understanding of chemical reactions and catalysis at an unprecedented level of detail.

The imaging work is described today in the journal Science.

Fluorescence reveals temperature changes inside living cells. Credit: ACS

Looking beyond the genetics and proteomics of individual cells to examine properties that might seem less important can actually lead to some interesting results.

For example, researchers who poked cells with the tip of an atomic-force microscope (AFM) found that aggressive cancer cells are softer than their healthy counterparts--a property that may help them journey through the circulatory system to spread the disease. In this way, AFM technology, traditionally one of the tools of mechanical engineers and materials scientists, may help doctors determine how aggressive a patient's cancer is. As TR reported last week, the same microscopy technique is also being used to study osteoarthritis in its early stages.

Now researchers at the University of Tokyo have developed an imaging probe that takes individual cells' temperature to within half a degree centigrade. As the temperature rises, the probe--a green fluorescent dye encased in a nanogel--shines more brightly. The Japanese researchers haven't worked out how measuring a cell's temperature might help clinicians deal with disease. But the findings were somewhat surprising, according to an outside researcher contacted by Chemistry World. The article quotes Prasanna de Silva from the University of Queens, who was not involved in the research:

"I think people might have felt before that temperature was not worth measuring," [says] de Silva, "because we expect it to be held constant most of the time. We are beginning to realise that, while the cell's buffering mechanisms do eventually work, there are short-term local effects. So if you can watch a cell in small spatial detail, with good time resolution then you can pick up on things which wouldn't be seen otherwise."

The temperature-sensitive probe is described this week in Journal of the American Chemical Society. The researchers speculate that diseased cells may run slightly hotter because of increased metabolism, and they hope to formulate the temperature probe so that cells can be monitored as they grow.

Last year, I wrote about another research group using voltage-sensitive dye nanoparticles to study the electrical fields inside cells, which can be as strong as lightning bolts. It's not yet clear just what the implications of either imaging technique will be. But for the voltage-sensing story, I talked to Piotr Grodzinski, director of the National Cancer Institute Alliance for Nanotechnology in Cancer, who emphasized the importance of studying cancer at the cellular level. Here's a snippet from that article:

Grodzinski says that many developments in cancer research over the past few years have been "more reactive," working toward developing diagnostics for catching the disease in its earlier stages and for better predicting to which drugs patients will respond. Despite how far cancer treatments have come, the way that cancer progresses at the cellular level is still not very well understood. With a better understanding, researchers hope to further improve diagnostics and personalized care. "This development represents an attempt to start using nanoscale tools to understand how disease develops," says Grodzinski.