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.

Nanostructures in this 40 million year-old feather once made it iridescent. Credit: Jakob Vinther/Yale University

By using an electron microscope to examine nanoscale structures in a 40 million-year-old bird feather, researchers have determined that, in life, the birds were black with an iridescent, bluish-green coppery sheen, like starlings and grackles. The key to figuring this out was the discovery by researchers at Yale University that rod-shaped nanostructures in the feather specimens aren't bacteria, but remnants of pigment-containing cells called melanosomes.

Iridescence in bird feathers is caused by constructive interference of light scattered by the cells; how the light scatters is determined by the arrangement of the melanosomes, which are preserved not only in the bird fossils but in some dinosaur and mammalian ones as well. The Yale researchers hope this technique could be used to get a better picture of the coloring and patterning of dinosaurs and other extinct creatures. This work is described online in the journal Biology Letters.

Laser light was focused on the region of this mouse cell indicated by the red dot, activating a hybrid version of a protein called Rac and causing the cell to change shape and move. Credit: Yi Wu, UNC-Chapel Hill

Researchers at the University of North Carolina in Chapel Hill and the Max Planck Institute in Heidelberg, Germany have genetically engineered animal cells to make proteins that can be turned on and off using visible light.

The researchers spliced a gene for a light-activated protein with the gene for a protein called Rac, which is known to be involved in regulating healthy cell movements as well as the movement of cancer cells. Researchers then focused laser light to locally activate the proteins, causing protrusions that led to cell movement. The work was described this week in the journal Nature.

The location of a protein within the cell plays a role in determining the cell's behaviors, but this has been difficult to study. The researchers hope using light activation will be a good method.

Here's how it works: the light-activated portion of the protein blocks the binding site on Rac. When it's illuminated, the block is removed and Rac can function. A second pulse of light at a different wavelength causes the block to move back into position, deactivating the protein.

The technique should be compatible with other proteins in addition to Rac. In the past, researchers have made proteins that are activated by ultraviolet radiation, which is toxic to cells. And these previous proteins couldn't be turned off again; the new ones can.