|
|
 |
|
|
|
|
|
Spatial
Phase Imaging
Industrial Productivity and Manufacturing Technology
Originating Technology/NASA Contribution
In 1928, Alexander Fleming, a young Scottish scientist with
a side practice of discretely treating the syphilis infections
of prominent Londoners, was researching agents that could
be used to combat such bacterial infections. He left his
practice for a 2-week vacation, inadvertently leaving several
bacterial culture plates unwashed and out of the incubator.
When he returned, what immediately struck him was that the
plates had grown mold, but the bacteria Fleming had been
working with was being fended off by the mold, which he called
penicillin, after the mold Penicillium notatum. Although
unable to refine or purify the penicillin, Fleming had discovered
the archetype of modern antibiotics.
The days of chance drug discovery and extensive trial-and-error
testing are over, though. Drugs are not really discovered
in this fashion anymore; rather, they are
now designed.
Understanding proteins, the basic biological building blocks
for all animals (including humans) and the regulators of
biochemical processes in plants, helps researchers design
these new drugs, combat diseases, and even improve agricultural
products, such as pesticides. Researchers are unlocking this
knowledge by studying the growth of protein crystals.
Through such study, researchers can now target a specific
protein of a pathogen to maximize a drug’s effectiveness,
while at the same time work to minimize possible side effects.
This process, known as rational drug design, has one major
downside: The exact structure of the target protein must
be determined, down to the last molecule.
|
Crystallization
trial of the glucose isomerase enzyme pseudo-colored
by the phase of light from a slurry/crystal mixture
and captured in 3-D. |
To uncover this molecular structure, scientists often use
X-ray crystallography. A crystal of the protein is bombarded
with X-rays to produce a pattern, which, much like a fingerprint,
reveals the identity of the protein’s atomic structure. To
get an accurate pattern, though, the crystal must be as free
of imperfections as possible. Growing such crystals can be
extremely difficult—even impossible—on Earth, because gravity
causes the crystals to settle on top of one another, which
results in structural flaws.
Since 1985, to take advantage of the ability of crystals
to grow free of imperfections in microgravity, a variety
of protein crystal growth experiments have flown on the space
shuttle, and several have flown on the International
Space Station (ISS).
Data collected from the ISS experiments allowed the comparison
of growth rates and crystal quality of microgravity versus
Earth-grown crystals. The crystals that are grown in microgravity
are able to grow larger and better organized than on Earth.
The research that is done on these crystals may further human
space exploration efforts by technological and biological
advancements developed as a direct result from this research
and will likely lead to the newest generations of wonder
drugs.
Partnership
Frequently, scientists grow crystals by dissolving a protein
in a specific liquid solution, and then allowing that solution
to evaporate. The methods used next have been, variously,
invasive (adding a dye that is absorbed by the protein),
destructive (crushing protein/salt-crystal mixtures and observing
differences between the crushing of salt and protein), or
costly and time-consuming (X-ray crystallography).
In contrast to these methods, a new technology for monitoring
protein growth, developed in part through NASA Small
Business Innovation Research (SBIR) funding from Marshall
Space Flight Center, is noninvasive, nondestructive, rapid, and more cost
effective than X-ray analysis. The partner for this SBIR,
Photon-X, Inc., of Huntsville, Alabama, developed spatial
phase imaging technology that can monitor crystal growth
in real time and in an automated mode.
Spatial phase imaging scans for flaws quickly and produces
a 3-D structured image of a crystal, showing volumetric growth
analysis for future automated growth. It can measure the
characteristics of a crystal and the crystal’s 3-D volumetric
properties, and can also discriminate between salt and protein
crystals.
The spatial phase imaging involves the use of proprietary
filters. The operator uses a single camera to acquire a series
of spatial phase images of a specimen—which could include
one or more protein crystals mixed with one or more salt
crystals. The next step is to digitally process the image
data using algorithms that extract information on the 3-D
properties of the protein crystal of interest, including
its volume and some aspects of its crystalline structure.
This information can be processed further to extract information
about the symmetry of the crystal and to detect flaws.
The method is not expected to eliminate the need for X-ray
crystallography at the later stages of research. However,
as a means of identification and preliminary analysis of
protein crystals, it could eliminate or greatly reduce the
need for X-ray crystallography as a screening technique in
the early stages. In addition to being noninvasive and nondestructive,
the new method yields results so rapidly that it is suitable
for real-time monitoring and, hence, for providing process
control feedback. This method is expected to accelerate the
search for conditions to optimize the growth of proteins
and to be a means of automation of the growth of high-quality
protein crystals.
Product Outcome
While the target market for Photon-X’s spatial phase imaging
technology includes pharmaceutical companies, as well as
laboratories at the academic, commercial, structural, and
governmental levels, this technology is very desirable to
anyone who routinely sets up hundreds or thousands of crystallization
experiments on a daily basis, and it is more cost effective
than X-ray analysis.
|
Photon-X’s
3-D camera technology can capture a 3-D image in
single camera frame time. One application, face verification
software, has been successfully demonstrated and
shown to be a strong 3-D face verification tool. |
Photon-X has also used this innovative technology to develop
commercial 3-D cameras for various machine vision and automated
3-D vision systems. Its Spatial Phase Video Camera is able
to extract 3-D information passively without scanned or structured
lighting. This technology requires a single camera, a single-image
capture, and is independent of range. The 3-D output is smooth
and connected, with versatility and depth precision often
exceeding that of triangulation-based methods. Plus, by eliminating
the need for multiple camera angles, laser illumination,
or moving targets to generate usable data, machine vision
systems based on the sensor technology can be less expensive
and easier to install, and as passive devices, present no
laser radiation hazard to personnel.
The Photon-X 3-D spatial phase imaging system can rapidly
provide highly accurate data about the surface features of
its target. This information can be processed by existing
applications to determine the area, volume, or height of
surface features. This patented, innovative approach to characterizing
surface elements is angle-invariant and easily scaled to
suit a variety of applications, meaning that surface features
can be recognized at a variety of distances and angles.
By simply changing its field of view, the technology has
been successfully demonstrated in systems whose imaged targets
range in size from microscopic crystals, to faces, automobiles,
and aircraft; even to terrain features measuring hundreds
of yards in width at distances up to several miles from the
sensor unit itself.
Specific applications include machine vision, many different
types of inspection, rapid prototyping, target or object
recognition, surface damage assessments, deformation analysis,
defect detection and characterization, terrain mapping, and
biometric facial recognition, which analyzes a person’s facial
characteristics through digital video input. The images can
be used to construct intricate composites, which are then
stored in a database. This method of identification is currently
being used for security systems, but law enforcement agencies
are now exploring its application in terrorist and criminal
recognition.
|
|
|
|
