Design - April 2009
Vibration isolation critical to measuring neuronal
in the brain
Isolating a laboratory's sensitive microscopy equipment against
low-frequency vibration has become increasingly more vital
to maintaining imaging quality and data integrity for neurobiology
researches. Ever more frequently, laboratory researchers are
discovering that conventional air tables and the more recent
active (electronic) vibration isolation systems are not able
to adequately cancel out the lower frequency perturbations
derived from air conditioning systems, outside vehicular movements
and ambulatory personnel.
Such was the case with the department of physiology and biophysics
at Georgetown Univ. Medical Center, where Jian-Young Wu has
been conducting research on waves of neuronal activity in
the neocortex of the brain.
Wu and his colleagues visualize wave-like patterns in the
brain cortex using a new method called voltage-sensitive dye
imaging. They use a special dye that binds to the membrane
of neurons and changes color when electrical potential changes
on the membrane of active neurons. The neuronal sample is
derived from slices of rat neocortex.
Schematic of a negative-stiffness
vibration isolator. Source: Minus K Technology.
The neocortex is the outer layer of the cerebral hemispheres
in the brain of mammals. Made up of six layers, it is involved
in higher functions such as sensory perception, generation
of motor commands and, in humans, language.
The neurons of the neocortex are arranged in vertical structures
called neocortical columns. These are patches of the neocortex
with a diameter of about 0.5 mm and a depth of 2 mm. Each
column typically responds to a sensory stimulus representing
a certain body part, or region of sound or vision. Researchers
postulate that the human neocortex contains about a half-million
of these columns, each of which contains -60,000 neurons.
The neocortex can be viewed as a huge web, consisting of billions
to trillions of neurons and hundred of trillions of interconnections.
While individual neurons are too simple to have intelligence,
the collective behavior of the billions of interneuronal interactions
occurring each second can be highly intelligent.
Traditionally, scientists have studied brain activity by placing
a few electrodes in the brain and measuring the electrical
signals of the neurons close to the electrodes. This method
is workable for understanding the function of the cortex and
interactions between individual neurons, but it is not suitable
for studying the emerging properties of the nervous system.
"It is like viewing a few pixels on a television screen
and trying to figure out the story," explains Wu. "Now,
with optical methods and voltage-sensitive dyes, we can visualize
the activation in a large area of the neocortex when the brain
is processing sensory information, similar to watching the
whole television screen."
"Voltage-sensitive dye is a compound that stains neuronal
membrane and changes its color when the neuron is excited,"
continues Wu. "This allows us to visualize population
neuronal activity dynamically in the cortex. We study how
individual neurons in the neocortex interact to generate population
neuronal activities that underlie sensory and motor processing
functions. Population activities are composed of the coordinated
activity of up to billions of neurons. Currently, we study
how oscillations and propagating waves can be generated by
small ensembles of neocortical neurons."
Viewing the spatiotemporal patterns of neuronal population
in the cortex is markedly different from recording individual
neurons. Here the cortical activity is viewed as "population
activity," that can be more complex than the linear addition
of an individual neuron's activity. Voltage-sensitive dye
and optical recording techniques give the neuroscientist a
new tool for figuring out how brain cortex works. (For details
on Wu's theories about spiraling wave patterns in the brain,
see the expanded edition: www.labdesignnews.com/april.)
Vibration isolation required
Since voltage-sensitive dye signals are small, usually a change
of 0.1 to 1 % of the illumination intensity, Wu's team has
used a high-dynamic-range camera, photodiode array to detect
the voltage-sensitive dye signals of the cortical activity.
The photodiode array can resolve extremely small changes in
light, usually one part of ten thousands. (Human eyes and
ordinary digital cameras register light changes of one part
to a hundred). Detecting such small signals requires an extreme
isolation of vibration. The lab had to contend with low-frequency
vibrations from air conditioning equipment, people walking
and wind blowing against the building. Vibrations as low as
1 Hz were inhibiting the integrity of the images and data.
"At first, we used high-quality air tables, but they
were not adequate for isolating low-frequency vibrations,"
Wu says. "We tried putting a second air table on top
of the first one, but that still did not give us the isolation
we needed. Then we tried an active, electronic system, but
we were still spending much time fighting with floor vibrations.
We were dealing with an unresolved vibration problem for many
The Georgetown lab eventually tested and settled upon negative-stiffness
mechanism vibration isolation systems from Minus K Technology,
which enabled the lab to get vibration isolation down to a
level of 1 Hz. This effectively cancelled out any vibration
noise difficulties that were inhibiting image and data readings.
Negative-stiffness mechanism (NSM) isolators have the flexibility
of custom-tailoring resonant frequencies vertically and horizontally.
They employ a completely mechanical concept in low-frequency
vibration isolation. Vertical-motion isolation is provided
by a stiff spring that supports a weight load, combined with
a NSM. The net vertical stiffness is made very low without
affecting the static load-supporting capability of the spring.
Beam-columns connected in series with the vertical-motion
isolator provide horizontal-motion isolation. The horizontal
stiffness of the beam-columns is reduced by the "beam-column"
effect. A beam-column behaves as a spring combined with a
NSM. The result is a compact passive isolator capable of very
low vertical and horizontal natural frequencies and very high
internal structural frequencies.
Transmissibility with negative-stiffness is substantially
improved over air systems, which can make vibration isolation
problems worse since they have a resonant frequency that can
match that of floor vibrations. Transmissibility is a measure
of the vibrations that transmit through the isolator relative
to the input vibrations. The NSM isolators, when adjusted
to 0.5 Hz, achieve 93% isolation efficiency at 2 Hz; 99% at
5 Hz; and 99.7% at 10 Hz.
NSM transmissibility is also an improvement over active systems.
Because they run on electricity, active systems can be negatively
influenced by problems of electronic dysfunction and power
modulations, which can interrupt scanning. They also have
a limited dynamic range-which is easy to exceed-causing the
isolator to go into positive feedback and generate noise underneath
the equipment. Although active isolation systems have fundamentally
no resonance, their transmissibility does not roll off as
fast as with negative-stiffness isolators.
Within the past 10 years, Wu's team has documented a variety
of waveforms (e.g., plane wave and spirals) in brain slices
during artificially induced oscillations. Using neocortical
slices and mathematical models, they are studying the initiation
of the waves and the factors that control their propagating
direction and velocity.
The lab is also involved in the development of new optical
imaging techniques-relying on the negative-stiffness vibration
isolation systems-such as imaging propagating waves in vivo,
in intact brains. "This is technically difficult,"
says Wu. "Other imaging methods (MRI, PET or MEG) provide
inadequate spatiotemporal resolution. Large-scale neuronal
activity is a hallmark of a living brain. We are improving
the optical imaging techniques with a hope to visualize the
waves in the cortex in vivo during sensory processes and in
awake animals while behavioral and cognitive tasks are performed."
Source: Minus K Technology Inc. (www.minusk.com). The company
develops, manufactures and markets state-of-the-art vibration
isolation products based on patented negative stiffness-mechanism
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