The fundamental understanding of cerebral systems and associated diseases relies on the electrical recording of single neuron activity. This requires in vivo interfacing with neurons using micrometer-scale electrodes. Traditionally, this challenging task is being performed using: single wire electrodes, probes containing small ensembles of electrodes or, more recently, multi-electrode arrays. These electrode arrangements have the potential to gather signals in three-dimensional space and to provide important laminar information. However, the types of arrays that have been proposed so far are either restricted to sampling in a given plane or have difficulty in collecting data in complex regions, such as those found in highly convoluted cortices. Moreover, state-of-the-art micro-electrode systems are not (yet) suitable for obtaining highly stable signals over extended recording periods. In some cases, the probes are just too bulky to follow cortical motion in chronic applications. Also, the damage inflicted to tissue and the way tissue responds to the presence of a foreign body are presently restrictive to chronic neural recordings. Such a chronic use is, however, highly needed, since it allows the study of changes in population activity at single neuron level and at the interaction level with learning, memory and training.

Figure 1. Illustrations of the modular integration technology and interconnect technique used in NeuroProbes.
To deal with these shortcomings, European technologists, scientists and industrialists have gathered forces in the NeuroProbes project, funded by the European Commission and coordinated by IMEC. Their goal is ambitious – to develop a new generation of microprobe arrays that addresses the above challenges and incorporates additional functions in one system.

NeuroProbes – An Integrative Concept

At the heart of the NeuroProbes concept is a unique microsystem integration solution that enables a modular integration of diverse features into a common platform. In essence, arrays are assembled in a modular fashion similar to the way Lego® bricks are put together. In this way, customization of arrays for diverse application conditions is possible for the first time with a combination of diverse functions: electrical recording and stimulation, drug delivery, and chemical sensing. Probes of different functionalities, dimensions and configurations can be interchangeably assembled to the array.

The probe arrays are assembled perpendicularly into a backbone using a novel out-of-plane interconnect technique. The individual probe arrays, also known as combs, are made of needle-like structures (or shanks) that are manufactured in silicon using deep reactive ion etching. Their fabrication process is compatible with CMOS fabrication.

Each probe shaft contains a number of electrodes. The resulting probe array has a slim profile which is conducive to a floating operation for chronic use in the brain. The probe arrays are sequentially assembled into a backbone leading to a three-dimensional electrode distribution. The interconnect consists of a gold blade which hangs over the edge of a cavity in which a probe is inserted. Once the probe is inserted into the cavity, electrical contact through mechanical caulking is established between the gold blades on the backbone and matching gold tracks on the probe.

The assembly process is done using a flip-chip bonder. The resulting interconnect density can be currently pushed to a pitch of 35μm. During assembly, both electrical and mechanical connections are established. The electrical connection between probes and external circuitry is performed via highly flexible ribbon cables that are consistent with the floating character of the entire set up (Figure 1).

An innovative concept is introduced to accurately position the probes with respect to the individual neurons. Therefore, a large number of electrodes (e.g. 512 electrodes on 8mm probes) are implemented per probe and the best electrode locations are determined by electronically scanning the electrodes. This electronic depth control can be implemented thanks to the modular approach adopted in NeuroProbes, which allows the integration of electronics both along the probe shaft and on the array backbone. In contrast to other methods, no mechanical motion is used to achieve the desired proximity between electrodes and neurons.

Presently a series of probe array prototypes has been implemented, and acute and chronic tests are being carried out. A prototype of a telemetry unit has also been completed for evaluation purposes (Figure 2).

NeuroProbes Architecture Potential

Figure 2. Complete system assembly, showing a probe array with a 4x4 array of 8mm long probes.
The modularity approach used in NeuroProbes yields several key differentiators that were never before available to neuroscientists. It opens avenues beyond the classical recording of single neuron activity. Having three-dimensional recording capability by itself will permit the most complete mapping of local circuitry in the brain to date. By modularly combining multiple features into a common platform, it offers the possibility of tailoring probe configuration to specific experimental or clinical needs. Probe modularity is also important for accessing complex regions of the brain. It becomes easier to adjust electrode distribution according to a specific complex area such as the sulci of highly folded cortices.

Chemical sensing and drug delivery are also important features of the NeuroProbes concept. Drug delivery enables, for instance, the inactivation of specific regions of the brain while mapping neighboring or connected regions. Further, it will be possible to deliver neuroactive compounds such as modulators and neurotransmitters during single neuron recordings, so that application sites are guided by electrical mapping and the effects of agents are directly observed. Finally, the integration of biosensors and electrical probes within the same platform provides 3D spatial correlation never available before.

Neuroprobe platform with probe array.
Special emphasis is also given to long-term chronic use of the probes. The high stability for chronic use will allow the study of changes in population activity at single neuron level and the way it relates to learning, memory, and training of the individual. In this context, NeuroProbes investigates active methods to control gliosis at the molecular level so that electrodes remain functional while the probes are stably anchored to tissue. Currently, a combination of diverse strategies for the management of foreign body reaction is being investigated within the project. The project also addresses the specific issue of probe array insertion, in an effort to minimize tissue damage and scarring. Equally important, the overall probe implementation – including cables – is fully conducive with floating operation.

By electronically adjusting electrode placement, individual control of electrode positioning with respect to single neurons becomes feasible. With this technology, positioning does not rely on trial and error and leads to a much larger number of working electrodes.


The multifunctional probe arrays will allow an extremely wide series of innovative diagnostic and therapeutic measures for the treatment and for the scientific understanding of cerebral systems and associated diseases. For example, the microfluidic capability will have an enormous impact on furthering the understanding of the organization of the prefrontal cortex, which, in turn, could be valuable in the research of disorders such as attention deficit hyperactivity disorder. Other medical applications include the study of the early cognitive decline in Alzheimer’s disease and the management of epilepsy. Also being investigated is the use of this system in auditory and visual prosthetic systems.

What we have here is an integrative concept to build microprobe arrays for cerebral applications. The proposed architecture allows the integration of advanced features such as microfluidic channels for drug delivery, fine depth control, telemetry, and biosensors to ultimately provide electrical recording and stimulation as well as chemical sensing and stimulation. The probes are manufactured compatibly with CMOS fabrication and an electronic depth control mechanism allows their accurate placement with respect to neurons. The proposed architecture will eventually enable a new set of tools for neuroscience research and clinical use. Having three-dimensional recording capability by itself will permit the most complete mapping of local circuitry in the brain to date. Also envisioned are immediate medical applications such as neuroprosthesis and the management of brain disorders such as epilepsy.

This article was written by Mieke Van Bavel, PhD, Scientific Editor, IMEC (Leuven, Belgium). For more information, contact Mr. Van Bavel at This email address is being protected from spambots. You need JavaScript enabled to view it., or visit .