Chipping away at cell mysteries

October 05, 2021

By Maggie Chen

RFID probes can relay information to researchers from inside a living cell.

Each of our cells is an evolutionary machine of unresolved mysteries – full of quirky specialized structures floating in a thick jelly. Stanford University researchers have now developed a tiny wireless chip that can go inside the cell to report evidence on some of those mysteries.

A team led by electrical engineers Ada Poon and H.S. Philip Wong has created a chip system based on radio frequency identification device (RFID) technology, similar to the RFID tags found on everything from retail items to subway passes. Their system, described in a March Scientific Reports paper, wirelessly connects a specialized RFID that goes inside the cell with an outside transceiver.

After manipulating the cell’s surroundings, researchers can gather information on how the cell reacts. By coating the RFID with different materials, scientists can train the chip to sense alteration in cell attributes such as pressure, acidity or the presence of certain molecules.

Each RFID consists of a capacitor, which stores electrical energy, surrounded by an antenna. To customize the RFIDs, different electrical characteristics can be synthesized. To then identify individual RFIDs, researchers engineered a device in which droplets of cell solution are brought within range of a detecting transceiver.

The RFID probes enter cells through a process known as phagocytosis, in which the cell engulfs a small dollop of the surrounding environment. The devices are only 1.5 micrometers thick with a diameter of 25 micrometers – not much smaller than the diameters of the mouse melanoma cells used in the study. Once inside, the RFID chip sits snugly within the confines of the cell membrane. Previous research by Poon and Wong suggests that the chip does not negatively affect cell survival or metabolism, allowing the cell to carry on its normal activities.

An intracellular device carrying an antenna “would be magnificent,” says José Antonio Plaza, head of the Micro- and NanoTools Group at the Institute of Microelectronics of Barcelona, who was not involved in the study. Plaza’s laboratory has studied the intracellular mechanics of embryo development by incorporating force-sensing chips into mouse embryos and viewing them through microscopy, in work published in a 2020 Nature Materials article.

Excitingly, the Stanford RFID system can also be powered to perform specific tasks. This chip “actuation” works much like wireless phone payments based on RFID technology, in which a payment station can energize or pass information to a chip inside the phone, Poon says.

Jihun Rho, a postdoctoral scholar spearheading the project, wants to optimize this function for drug delivery. Rho explains that an RFID chip pre-loaded with drug molecules could be powered to eject the molecules into the cell.

Her team is testing this concept with a "rho kinase inhibitor" drug that can change the movements of a cell. Rho aims to eventually control cell movement as a proof-of-concept – using the chip to steer the cell around a Petri dish like one might drive a car.

Another experimental ambition is to combine sensor and actuator chips in the same cell. This approach potentially would allow for modulation of signaling within the cell, thus affecting its behavior.

Additionally, the researchers are looking at applications in cancer therapeutics. Cancer cells naturally undergo more phagocytotic activity because they divide more than normal cells. This conveniently causes cancer cells to uptake more RFIDs than normal cells, Poon says.

She describes the proposed approach as “suicide bombing” – self-destructing the RFID once it is ingested inside a cancer cell ideally would destroy the cancer cell itself. “Building circuits to burn is much easier than building circuits that do not burn,” Poon says with a laugh.

Right now, the researchers say, it is not feasible to incorporate these systems into human or animal bodies, one hurdle being that the detecting transceiver must be within millimeters of the RFID probe.

However, the Stanford team already is collaborating with biochemist Wallace Marshall’s laboratory at the University of California, San Francisco to apply this technology towards learning about how cells “make decisions.”

“The vision of this chip is that it will allow us to not only measure molecular events inside the cell in real time as the cell moves around and does its various behaviors, but will also let us inject our own signals into the cell,” Marshall explains.

Poon, Rho and Plaza hope that future intracellular chips will reveal many such cellular secrets. “This technology is in its infancy,” comments Plaza. “But in the near to medium future, it will be interesting to find answers to some fundamental questions about the cell.”

Maggie Chen studies developmental biology and the history of science at Harvard College. She is a freelance science writer with contributions to BioSpace, Massive Science and the New York Times. As an undergraduate research fellow at the Harvard Stem Cell Institute, Maggie works on finding ways to mend broken hearts. She can be found on Twitter @chenmaggiesy.

This story was produced as part of NASW's David Perlman Summer Mentoring Program, which was launched in 2020 by our Education Committee. Chen was mentored by Eric Bender.

Maggie Chen

Main image: The RFID chip inside this mouse melanoma cell can transmit information about the cell, which may eventually help to answer many questions in biological research. Credit: Mimi Yang, Ada Poon and H.S. Philip Wong, Stanford University.