Scientists from the UK have figured out how to use a force field to separate cells, and it’s about to change prostate cancer research. It’s done with an “electric sieve” that began its life as a bit of aluminum foil with some epoxy smeared on it. This new, sci-fi approach is based on another research technique called “dielectrophoresis.”
To date, the major use case for dielectrophoresis has been DNA sequencing. Sanger sequencing, the cornerstone of DNA sequencing for decades, depends on dielectrophoresis to organize mixed-up bits of DNA so we can read them and put them in the right order. It does this by putting a trickle of electrical current through a bit of agar gel that’s floating in an electrolyte bath.
The current drags the bits of DNA, at rates according to their size. But the voltage required to move DNA through an agar gel is not the same voltage that living cells want to experience in their day-to-day. So until very recently, we couldn’t use this technique to separate different types of living cells and expect them to still be alive afterward, let alone still doing their thing like they had been before.
Separating Entire Cells
Now, researchers from the University of Surrey have figured out how to use electricity to separate not just bits of DNA, but entire cells. Because the idea depends on passing current through a sample, the team of researchers started out with a bit of aluminum foil held down with epoxy glue, and ended up with a By carefully varying the materials and electrical current applied to their dielectrophoresis rig, they found the right physical setup: a chip that uses 3D electrodes. The researchers discovered that they could use an electrical force field generated by the chip to separate out different kinds of cells — particularly, they could sift apart cancer cells from normal cells.
Doing it the above way means that scientists can avoid using chemical agents in their efforts to sieve out certain kinds of cells from a sample. It’s cleaner, faster, less expensive, and more efficient. The team thinks they can get the chip setup to a point where it’s cheap enough to be disposable, because it doesn’t require sophisticated lab-on-chip components — just electrodes.
It all starts by exploiting the unique electrical properties of different kinds of cells. Normal, healthy cells are different from cancer cells in a bewildering variety of ways. A normal, garden-variety cell in your body is well-organized in its physical form, with neat boundaries and strong connections to its neighbors. Healthy cells also know when to stop growing; when the body fills in a wound with cells, it knows to quit putting new cells there because of a thing called “contact inhibition.” Cells can obey contact inhibition because they’re capable of receiving signals across their cell walls. But cancerous cells have a messed-up membrane, with too many functional groups tacked on in places they have no business being. A phosphate group here, an amino group there, and all of a sudden the whole membrane has different electrical characteristics.
What does it mean for cells to have different electrical characteristics? Consider electrostatics. If you place a test charge, +Q, somewhere in a non-uniform electrical field that has a (+) side and a (-) side, that test charge will drift toward the (-) side according to the magnitude of the charge (how big of a number Q is) and the “steepness” of the field gradient.
This works exactly the same all the way down to the single-atom scale. Atoms have different electrical charges depending on how many electrons they have available in their outermost valence shell. So, not only do they tend to diffuse away from regions of high chemical concentration toward regions of lower concentration, but they also move in accordance with whatever prevailing electrical field they’re being exposed to.
Cells are made of atoms, and your body is made of cells. Normally, your body has an aggregate neutral charge: the positive charges usually balance out the negative charges, leaving you neutrally charged with respect to the outside world. But when cancer starts sending its wretched tendrils through the body, it changes every cell it touches. And different cancers have different (but predictable) patterns of alteration to the cells they attack.
Fighting Prostate Cancer
Prostate cancer is no exception. One difference between normal and cancerous prostate cells is that where normal prostate cells use zinc to carry out their biologically ordained function, prostate cancers are devoid of zinc. Their membranes will have different functional groups attached to their component phospholipids, too, compared with normal prostate cells. That results in a cell with a slightly different charge than normal, compared with whatever’s outside it. And it’s the same kind of charge, Q, that we work with in electrostatics. These telltale differences in electrical charge mean that cancerous cells will move differently than normal cells, when exposed to an electrical field. It’s like cancer was playing poker, and it has a “tell.”
The force fields can be used to separate different kinds of cells that are suspended in many different media, including blood or urine or just in a regular petri dish. The implications are far-reaching. It could be used to separate cells for purposes of diagnosing prostate cancer, and it also has immediate applications in research — not just for cancer, but for other diseases including Alzheimer’s. Being able to quickly and easily separate out cells means that researchers can get right to their targets. Anything that makes cancer research faster and easier is going to be a benefit.