Researchers craft cell-level implants
IMEC growing its efforts in bio-electronics
(10/20/2008 12:01 AM EDT)
LEUVEN, Belgium — IMEC has created a novel brain implant chip that uses CMOS to provide a Lego-like platform for plugging in arrays of tiny devices each sporting hundreds of contacts. The European research group also is developing a handful of techniques to interface electronics with the body, some of them working at the level of individual cells.
The efforts are part of a broad industry trend to expand the benefits of implanted electronics down to the molecular level. Researchers believe nanometer-scale electronics will be able to provide highly refined and personalized diagnosis and therapies.
Much of the work is still at the basic research level. Researchers are crafting the devices in lab experiments with cultures and animals, hopeful of many potential applications but unsure exactly how or when they will be used in humans.
Brian implant chips, for example, “don’t necessarily improve the quality of life yet,” said Chris Van Hook, a program director for smart implants at the Leuven, Belgium-based group.
Asked what is the path from research to commercialization for some of the medical efforts, Carmen Bartic, a group leader in bio-electronic systems at IMEC, replied, “that’s what I’d like to know.”
Nevertheless, IMEC got a lead in some respects over research on brain implants in two American universities, said Van Hook. The IMEC chip uses an array of 16 shanks measuring two to eight millimeters long with as many as 500 contacts patterned on each shank.
By contrast researchers at universities in Michigan and Utah have demonstrated arrays that use only about a dozen shanks all of one length, each acting only as a single electrode capable of giving a charge.
The IMEC design can record brain signals in greater detail and apply therapies to more localized groups of cells. In addition, it can accommodate a variety of plug-in shanks, including hollow ones on the drawing board for 2010 that could deliver tiny dosages of chemicals directly to a neuron.
The ideal design would be able to record and process neural activity and deliver and electrical or chemical stimulus when it determines nerve cell behaviors need to change. “You want to have multi-functionality,” said Van Hook.
A handful of startups are working in brain implant chips, including ones spun out of the U.S. universities. At least one of those startups has trial implants in as many as six humans.
For its part, IMEC is evaluating whether it wants to create a spin-out company or joint venture based on its work. It has only tested its chip in lab animals to date.
Only a few hundred brain implant chips are sold each year at prices of about $1,000 each, almost entirely to academics conducting research. Long term, researchers hope the devices find a wide range of uses including stimulating muscle movements in handicapped patients and counteracting ailments including epilepsy, depression, obsessive-compulsive disorder and Parkinson’s disease.
One of the chief technical challenges is creating bio-compatible devices. “We are not state-of-the-art in that area, but this is a necessary competency to make the system work,” said Van Hook.
Indeed, the field of bio-compatible electronics is so broad and fundamental, IMEC has dedicated a group to work on it. “We try to functionally link biological elements such as cells with nano- and micro-fabricated solid-state devices and build functional interfaces that allow a bi-directional interchange of information between the two systems,” said Bartic.
IMEC has created probes ranging from one micron down to 250 nm in size. A human nerve synapse measures about 45 nm, Bartic said. Getting devices and interfaces down to the cellular level is an important goal because many diseases such as cancer are essentially cell-level phenomena. Drugs and stimulation delivered to the whole body, or even to groups of cells, are, by contrast, crude.
“It’s like using a hammer to hit all the cells at once,” said Van Hook, who is exploring use of micro-actuators on the shanks of his brain implants to better connect with individual cells.
Working at the cellular level presents an array of challenges.
Cells are “the most complex machines ever” said Kris Verstreken, who joined IMEC as a program director in biomedical electronics in May.
“Cell pathways are always interacting with the environment and their changing nature is something we have to adjust to,” he said, calling for a class of “inter-ware” products that would mate electronics and cells. “We need new tools to work at this scale.”
Much of the work in this area revolves are electronic interfaces because cells give off measurable electronic signals. However, researchers are still working on how to best capture the signals, separate their different components and interpret what they mean.
Other challenges include finding ways to isolate the electrical recording and therapeutic signaling functions of an electronic device. Using electricity to change cellular behavior is also tricky because stimulation requires high voltages to be effective, but devices need to use low power levels to avoid frying cells.
“All these technologies have contradictory requirements,” said Bartic.
“Chemical stimulation is much more effective than electrical work because one molecule of a neural transmitter binds to a cell and opens it,” she said, and cells naturally wash away any excess chemical used.
However, chemical stimulation is still just at the proof-of-concept stage, she added.
Despite the challenges, the group has made progress in a number of efforts at creating bio-electronic interfaces.
One experiment coats an electronic probe with a chemical that intentionally triggers the biological process called endocytosis where a cell tries to engulf and destroy a foreign object. “Imagine you trick cells to eat your chips, so you get the best contact,” said Bartic.
Another experiment attempts to identify cancer cells and discharge tiny metal particles that can be activated to irradiate the cancer cell. Yet another lays down a patterned surface ideal for growing certain kinds of neural cells that will excrete chemicals that influence the behavior of neighboring cells in a positive way.
Some of the efforts are focused on pure biological research. One IMEC platform ejects particles that cells consume. The particles can be tracked by imaging systems to gain new insights into the little known behaviors of organs inside the cell wall.
In this way “you can find the working mechanisms of some diseases or track the absorption of certain medications,” said Verstreken.
Thus many of these interfaces could be used in basic research labs in academia and in biotech and pharmaceutical companies. As researchers use such tools to learn more about the workings of neurons, they may be able to construct devices that replace nerve cells for a variety of disorders found in those who have suffered strokes, heart attacks or even depression.
“One could construct systems that could replicate the functions of multiple neurons on one chip,” said Bartic.
The bio-electronic work is relatively new at IMEC, having started about four years ago. As much as 80 percent of the funding comes from public sources such as European governments.
IMEC hopes to engage a broad group of companies interested in sponsoring individual projects, said Ludo Deferm, vice president of business development at IMEC. Building trust on focused projects should eventually lead to launching multi-year research programs with corporate partners, the model used to drive IMEC’s business in its core semiconductor process work, he said.
The group aims to draw in partners in medical electronics, biotech and pharma who would be new clients for IMEC. It also hopes to attract some of the new medical electronics divisions traditional IMEC partners such as Intel, Texas Instruments and other chip makers have setting up.
In this way, the medical work represents a strategic diversification for IMEC. The group is planning to make further investments in the field. Plans on the drawing board include erecting new buildings, in part to house IMECs medical and bio-electronic efforts.