Developing a Multi-Probe
Manipulator System for
By David Henderson,
New Scale Technologies
Avast amount of our understand- ing of the brain comes from inserting tiny metal wires to
eavesdrop on the electrical activity
generated by neurons. This technique,
known as extracellular electrophysiology, is becoming more powerful as the
latest silicon microfabrication processes allow engineers to pack more
wires into smaller probes. The latest
generation of silicon probes, developed by Imec (Leuven, Belgium), use
CMOS technology to fit 384 recording
sites onto a shank that’s thinner than a
To maximize the amount of useful
information that can be extracted from
these probes, they must be positioned
with a high degree of accuracy. Individual brain areas are small, sometimes
only tens of microns in diameter, and
must be targeted precisely across multiple experiments. In addition, it is often
desirable to use multiple probes simultaneously to observe the interactions
between neurons in different parts of
the brain. Each probe must be moved
independently to minimize damage to
delicate brain tissue.
In 2015, Dr. Josh Siegle of the Allen
Institute for Brain Science started development of a new experimental rig capable of inserting five Imec probes (with a
combined total of 1920 electrodes) into
the brain simultaneously.
“We needed a practical solution for
multi-probe, simultaneous measurements
of interactions among neurons distributed
throughout the brain,” Siegle explained.
“Many very interesting scientific ques-
tions can be investigated using this new
Siegle is highly experienced in devel-
oping tools for neuroscience research.
As a co-founder of the nonprofit orga-
nization Open Ephys, he is a leading
member of a community of neuroscien-
tists dedicated to sharing open-source,
field-tested software and hardware for
For the new advanced rig, Siegle needed compact, high-precision micro manipulators to move each probe in three axes
(X, Y, and Z). He needed them to be very
small to maintain a clear field of view
in front of the mouse. This allowed him
to record neural activity as the awake
animal responded to visual stimuli.
Siegle selected commercially available
piezoelectric micro stages and created
the first-generation five-probe rig. Each
probe was held in a custom-designed
3D-printed mount and attached to an
XYZ assembly of M3-LS Linear Smart
Stages from New Scale Technologies.
The X and Y axes are used to move
the probe tip outside the brain under
visual microscope control. The Z axis
is used to slowly insert the probe to a
precise depth in the brain while monitoring the electrical measurements.
Recording begins when the proper
location is reached.
In the first-generation rig, each
stage assembly was supported by an
infinitely-adjustable arm manufactured
by Noga Engineering Ltd. The arm is
used to place the probe at the proper
angle and initial location within six
millimeters of the final target location
above the mouse. The final probe
locations were commanded from a PC
by operating the 15 motorized stages
from a single Python API connected
to an Arduino board that generates the
ASCII commands to the SPI interface
to each stage.
This was made possible by the
embedded drive and control electronics
within each stage.
“Having the controllers embedded in
the stage was helpful in getting the set
up operating quickly,” Siegle said. “The
A close-up of the motorized stages.
(Image Credit: David Henderson)