Label-Free Cell Isolation: How does CytoRecovery’s technology work?

What is dielectrophoresis?

Author: Dr. Josie L. Duncan, PhD

Dielectrophoresis is an innovative technology that has been used advantageously for decades, but its underlying physics can be complex. To best understand dielectrophoresis practically, let’s start with an analogy. Take radio stations, for example. If you tune the radio to the classic rock station, people who love classic rock are most likely to gravitate towards that radio station. Similarly, people who love pop music or alternative music will gravitate towards radio stations playing their preferred music. Radio stations, after all, are just frequencies. Your favorite radio station isn’t just 103.7 or 95.1, it’s 103.7 MHz and 95.1 MHz. Though cells don’t necessarily have a preferred music genre, if we apply an electric field rather than play music, cells respond differently to the frequency of that applied electric field. Because of this phenomenon, cells can be separated based on their “preference” or bias toward or away from an electric field. The cell will express its preference by moving in response to the applied electric field as a result of the frequency, either toward or away from areas of high field gradient; this is known as dielectrophoresis or DEP.

 

Dielectrophoresis, by definition, uses a non-uniform electric field (i.e., an electric field gradient) to induce movement of a cell. A cell, though a biological entity, can also be considered an electrical body that carries charges. In the presence of an electric field, the charges will align accordingly with the electric field; this is called a dipole. In a uniform electric field, if a cell has a similar number of positive and negative charges, then the cell is pulled equally in opposite directions. If there is a non-uniform electric field, however, the force on each side of the dipole is unequal, forcing the cell to move in response to the field. The electrical properties of cells are frequency-dependent, which means the cell properties change based on the frequency of the applied AC field. As you tune the frequency of the electric field, the response of the cells of interest will change according to their electrical properties.

In a heterogeneous mixture, different cell types and subpopulations will respond uniquely at a single frequency. For example, at a single frequency, one cell type may get “trapped” meaning it moves towards the large field gradient and is held in place until the electric field is turned off. At this same frequency, other cell types will not respond as strongly or even move away from the areas of the highest electric field gradient allowing for separation from trapped cells.

Why might a cell “prefer” one frequency over the other?

For clarity, cells are, of course, not exhibiting subjective preferences based on reason or a charming melody. Rather, biophysical differences, such as their size, phenotype, morphology, and health, dictate how the cell may respond in the presence of an electric field. By strategically implementing DEP parameters of frequency and voltage (i.e. the electric field gradient), we have an endless amount of cell characteristics we can detect and exploit for separation purposes just by observing how the cell behaves as we alter the applied field. Thus, we can identify unique bioelectrical signatures.

How is CytoRecovery, Inc. implementing this technology?

CytoRecovery, Inc. has harnessed the innovation offered by DEP to sort and enrich cell populations based on their inherent biophysical differences – no label required! The CytoR1TM Platform consists of a powerful, high-voltage function generator capable of applying hundreds of volts for a wide range of frequencies creating wide flexibility for every cell sorting application. In addition to the generator, the CytoR1TM Platform incorporates an intricately designed microfluidic device, known as CytoChipsTM, that facilitates cell-sized pockets of dielectrophoresis for enhanced sensitivity. The design not only prioritizes efficient separation and enrichment of cell samples, but it also alleviates the stress of the electric field on cell viability and completely removes the need for a label to get differential cell responses.

 

Key Takeaways:

  • Dielectrophoresis (DEP) uses electric fields to move cells based on their innate and unique electrical properties, or their unique bioelectrical signature.
  • The electrical properties of cells are manifestations of their biophysical properties.
  • The CytoR1TM Platform allows for sorting and enrichment of cell populations without a label while maintaining cell viability and sample sterility.