The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called tissue microfluidics because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets. The proposed principles represent a paradigm shift in microfluidic technology in three important ways: Microfluidic devices are to be directly integrated with, onto, or around tissue samples, in contrast to the conventional method of off-chip sample extraction followed by sample insertion in microfluidic devices. Architectural and operational principles of microfluidic devices are to be subordinated to suit specific tissue structure and needs, in contrast to the conventional method of building devices according to fluidic function alone and without regard to tissue structure. Sample acquisition from tissue is to be performed on-chip and is to be integrated with the diagnostic measurement within the same device, in contrast to the conventional method of off-chip sample prep and subsequent insertion into a diagnostic device. A more advanced form of tissue integration with microfluidics is tissue encapsulation, wherein the sample is completely encapsulated within a microfluidic device, to allow for full surface access. The immediate applications of these approaches lie with diagnostics of tissue slices and biopsy samples e.g. for cancer but the approaches would also be very useful in comparative genomics and other areas of fundamental research involving heterogeneous tissue samples

Kartalov, Emil P.

Shibata, Darryl

Taylor, Clive

Wade, Lawrence A.

NASA Technical Reports Server

NASA Tech Briefs, July 2011 33
Bio-Medical
A cytometer now under development
exploits spatial sorting of sampled cells
on a microarray chip followed by use of
grating-coupled surface-plasmon-reso-
nance imaging (GCSPRI) to detect the
sorted cells. This cytometer on a chip is
a prototype of contemplated future
miniature cytometers that would be suit-
able for rapidly identifying pathogens
and other cells of interest in both field
and laboratory applications and that
would be attractive as alternatives to con-
ventional flow cytometers.
The basic principle of operation of a
conventional flow cytometer requires
fluorescent labeling of sampled cells,
stringent optical alignment of a laser
beam with a narrow orifice, and flow of
the cells through the orifice, which is
subject to clogging. In contrast, the prin-
ciple of operation of the present cytome-
ter on a chip does not require fluores-
cent labeling of cells, stringent optical
alignment, or flow through a narrow ori-
fice. The basic principle of operation of
the cytometer on a chip also reduces the
complexity, mass, and power of the asso-
ciated laser and detection systems, rela-
tive to those needed in conventional
flow cytometry.
Instead of making cells flow in single
file through a narrow flow orifice for se-
quential interrogation as in conven-
tional flow cytometry, a liquid contain-
ing suspended sampled cells is made to
flow over the front surface of a microar-
ray chip on which there are many cap-
ture spots. Each capture spot is coated
with a thin (≈50-nm) layer of gold that is,
in turn, coated with antibodies that bind
to cell-surface molecules characteristic
of the cell species of interest. The multi-
plicity of capture spots makes it possible
to perform rapid, massively parallel
analysis of a large cell population.
The binding of cells to each capture
spot gives rise to a minute change in the
index of refraction at the surface of the
chip. This change in the index of refrac-
tion is what is sensed in GCSPRI, as de-
scribed briefly below. The identities of
the various species in a sample of cells is
spatially encoded in the chip by the pat-
tern of capture spots. The number of
cells of a particular species is deter-
mined from the magnitude of the GC-
SPRI signal from that spot.
GCSPRI as used here can be summa-
rized as follows: The cytometer chip is
fabricated with a diffraction grating on
its front surface. The chip is illumi-
nated with a light emitting diode (LED)
from the front. By proper choice of
grating parameters and of the wave-
length and the angle of incidence of a
laser beam, laser light can be made to
be coupled into an electromagnetic
mode that resonates with surface plas-
mons and thus couples light into sur-
face plasmons. Coupling of light into a
surface plasmon at a given location re-
duces the amount of incident light re-
flected from that location. A change in
the index of refraction at the surface of
a capture spot gives rise to a change in
the resonance condition. Depending
on the specific design, the change in
the index of refraction could manifest
itself as a brightening or darkening, a
change in the wavelength needed to ex-
cite the plasmon at a given angle of in-
cidence, or a change in the angle of in-
cidence needed to excite the plasmon
at a given wavelength.
Whereas a multiwavelength laser sys-
tem with multichannel detection would
be needed to detect multiple species in
conventional flow cytometry, it suffices
to use an LED and a single detector
channel in the GCSPRI approach: this
contributes significantly to reductions in
cost, complexity, size, mass, and power.
GCSPRI cytometer chips could be made
of plastic and could be mass-produced
cheaply by use of molding and other
methods adopted from the manufacture
of digital video disks. These methods are
amenable to a high degree of miniatur-
ization: such additional features as flu-
idic channels, reaction chambers, and
fluid-coupling ports could readily be in-
corporated into the chips, without incur-
ring substantial additional costs.
This work was done by Salvador M. Fer-
nandez of Ciencia, Inc., for Johnson Space
Center. Further information is contained in
a TSP (see page 1).
In accordance with Public Law 96-517,
the contractor has elected to retain title to this
invention. Inquiries concerning rights for its
commercial use should be addressed to:
Dr. Salvador M. Fernandez, President
Ciencia, Inc.
111 Roberts Street, Suite K
East Hartford, CT. 06108
Phone No.:(860) 528-9737
Fax No.:(860) 528-5658 
Refer to MSC-23711-1/4224-1, volume
and number of this Medical Design Briefs
issue, and the page number.
Cytometer on a Chip
Analyses could be performed rapidly in compact instruments using disposable chips.
Lyndon B. Johnson Space Center, Houston, TX
The principle of tissue microfluidics
and its resultant techniques has been ap-
plied to cell analysis. Building microflu-
idics to suit a particular tissue sample
would allow the rapid, reliable, inexpen-
sive, highly parallelized, selective extrac-
tion of chosen regions of tissue for pur-
poses of further biochemical analysis.
Furthermore, the applicability of the
techniques ranges beyond the described
pathology application. For example, they
would also allow the posing and success-
Principles, Techniques, and Applications of Tissue Microfluidics 
This technique can be used in the diagnosis of diseases such as cancer. 
NASA’s Jet Propulsion Laboratory, Pasadena, CA
https://ntrs.nasa.gov/search.jsp?R=20120000796 2019-08-30T18:42:58+00:00Z
34 NASA Tech Briefs, July 2011
ful answering of new sets of questions in
many areas of fundamental research. 
The proposed integration of microflu-
idic techniques and tissue slice samples is
called “tissue microfluidics” because it
molds the microfluidic architectures in
accordance with each particular structure
of each specific tissue sample. Thus, mi-
crofluidics can be built around the tissues,
following the tissue structure, or alterna-
tively, the microfluidics can be adapted to
the specific geometry of particular tissues.
By contrast, the traditional approach is
that microfluidic devices are structured in
accordance with engineering considera-
tions, while the biological components in
applied devices are forced to comply with
these engineering presets. 
The proposed principles represent a
paradigm shift in microfluidic technol-
ogy in three important ways: 
• Microfluidic devices are to be directly
integrated with, onto, or around tissue
samples, in contrast to the conven-
tional method of off-chip sample ex-
traction followed by sample insertion
in microfluidic devices. 
• Architectural and operational principles
of microfluidic devices are to be subor-
dinated to suit specific tissue structure
and needs, in contrast to the conven-
tional method of building devices ac-
cording to fluidic function alone and
without regard to tissue structure. 
• Sample acquisition from tissue is to be
performed on-chip and is to be inte-
grated with the diagnostic measurement
within the same device, in contrast to
the conventional method of off-chip
sample prep and subsequent insertion
into a diagnostic device. A more ad-
vanced form of tissue integration with
microfluidics is tissue encapsulation,
wherein the sample is completely encap-
sulated within a microfluidic device, to
allow for full surface access. 
The immediate applications of these
approaches lie with diagnostics of tissue
slices and biopsy samples — e.g. for can-
cer — but the approaches would also be
very useful in comparative genomics and
other areas of fundamental research in-
volving heterogeneous tissue samples. 
The approach advocates and utilizes the
bottom-up customization of microfluidic
architectures to biosamples, in contrast to
the traditional top-down approach of build-
ing the architectures first and then putting
the biosamples inside. Further, as particular
embodiments of the above principle, novel
techniques of sub-sample selection and iso-
lation are presented. These techniques
would have wide applicability in fundamen-
tal research and biomedical diagnostics. 
In particular, an in situ microfluidic
technique of single-cell isolation, or multi-
ple single-cell isolations, is described, and
is performed upon tissue sections at-
tached to pathology glass slides. The tech-
nique combines the advantages of preserv-
ing the architectural integrity of the tissue
section while allowing flexibility and preci-
sion of cell selection, rapid prototyping,
and enhanced sample purity, while bene-
fiting from the experience of the patholo-
gist in the selection process. The result is a
system that would allow the rapid and reli-
able biochemical analysis and diagnosis of
pathologic processes with sensitivity ex-
tended down to the level of even a single
cell, with high levels of confidence in the
diagnostic determination. 
These techniques would allow the ex-
traction of cells and cell nuclei chosen for
their potentially pathologic origin, e.g.
cancer. The chief advantages of the pro-
posed methods are their speed, ease, reli-
ability, and capacity to select individual
cells from a tissue slice population with a
higher degree of purity and specificity.
The result is the extracted DNA can be
biochemically analyzed with a higher de-
gree of diagnostic accuracy, as the iso-
lated sub-sample would not be diluted by
unwanted material from the ambient tis-
sue. In comparison to other techniques,
the proposed methods would combine
high specificity with high speed. 
This work was done by Lawrence A. Wade
of Caltech and Emil P. Kartalov, Darryl Shi-
bata, and Clive Taylor of the University of
Southern California for NASA’s Jet Propulsion
Laboratory. Further information is con-
tained in a TSP (see page 1).
In accordance with Public Law 96-517,
the contractor has elected to retain title to this
invention. Inquiries concerning rights for its
commercial use should be addressed to:
Innovative Technology Assets Management
JPL
Mail Stop 202-233
4800 Oak Grove Drive
Pasadena, CA 91109-8099
E-mail: iaoffice@jpl.nasa.gov
Refer to NPO-47561, volume and number
of this Medical Design Briefs issue, and the
page number.


Principles, Techniques, and Applications of Tissue Microfluidics

The principle of tissue microfluidics and its resultant techniques has been applied to cell analysis. Building microfluidics to suit a particular tissue sample would allow the rapid, reliable, inexpensive, highly parallelized, selective extraction of chosen regions of tissue for purposes of further biochemical analysis. Furthermore, the applicability of the techniques ranges beyond the described pathology application. For example, they would also allow the posing and successful answering of new sets of questions in many areas of fundamental research. The proposed integration of microfluidic techniques and tissue slice samples is called "tissue microfluidics" because it molds the microfluidic architectures in accordance with each particular structure of each specific tissue sample. Thus, microfluidics can be built around the tissues, following the tissue structure, or alternatively, the microfluidics can be adapted to the specific geometry of particular tissues. By contrast, the traditional approach is that microfluidic devices are structured in accordance with engineering considerations, while the biological components in applied devices are forced to comply with these engineering presets

20 NASA Tech Briefs, August 2011
cific application could be performed,
which would then match the characteris-
tics of the antenna with the protein sol-
der and tissue to best effect wound clo-
sure. An additional area of interest with
potential benefit that remains to be vali-
dated is whether microwave energy can
effectively kill bacteria in and around
the wound. Thus, this may be an effi-
cient method for simultaneously steriliz-
ing and closing wounds.
Using microwave energy to seal
wounds has a number of advantages
over lasers, which are currently in exper-
imental use in some hospitals. Laser tis-
sue welding is unsuitable for emergency
use because its large, bulky equipment
cannot be easily moved between operat-
ing rooms, let alone relocated to field
sites where emergencies often occur. In
addition, this approach is highly de-
pendent on the uniformity and thick-
ness of the protein solder as well as the
surgeon’s skills. In contrast, the use of
microwave energy is highly tolerant of
the thickness of the protein solder, level
of fluids in and around the wound, and
other parameters that can adversely af-
fect the outcome of laser welding. How-
ever, controlling the depth of penetra-
tion of the microwave energy into the
wound is critical for achieving effective
wound sealing without damaging the ad-
jacent tissue. In addition, microspheres
that encapsulate metallic cores could
also be incorporated into the protein
solder to further control the depth of
penetration of the microwave energy.
This work was performed by G. Dickey
Arndt, Phong H. Ngo, Chau T. Phan, and
Diane Byerly of Johnson Space Center; John
Dusl of Jacobs Sverdrup; Marguerite A. Sog-
nier of Universities Space Research Associa-
tion; and Jim Carl of Advanced Electromag-
netics. For further information, contact the
JSC Innovation Partnerships Office at (281)
483-3809.
This invention is owned by NASA, and a
patent application has been filed. Inquiries
concerning nonexclusive or exclusive license
for its commercial development should be ad-
dressed to the Patent Counsel, Johnson Space
Center, (281) 483-1003. Refer to MSC-
24238-1.
Principles, Techniques, and Applications of 
Tissue Microfluidics 
This technique can be used in the diagnosis of diseases such as cancer. 
NASA’s Jet Propulsion Laboratory, Pasadena, California 
The principle of tissue microfluidics
and its resultant techniques has been
applied to cell analysis. Building mi-
crofluidics to suit a particular tissue
sample would allow the rapid, reliable,
inexpensive, highly parallelized, selec-
tive extraction of chosen regions of tis-
sue for purposes of further biochemical
analysis. Furthermore, the applicability
of the techniques ranges beyond the de-
scribed pathology application. For ex-
ample, they would also allow the posing
and successful answering of new sets of
questions in many areas of fundamental
research. 
The proposed integration of mi-
crofluidic techniques and tissue slice
samples is called “tissue microfluidics”
because it molds the microfluidic ar-
chitectures in accordance with each
particular structure of each specific tis-
sue sample. Thus, microfluidics can be
built around the tissues, following the
tissue structure, or alternatively, the
microfluidics can be adapted to the
specific geometry of particular tissues.
By contrast, the traditional approach is
that microfluidic devices are struc-
tured in accordance with engineering
considerations, while the biological
components in applied devices are
forced to comply with these engineer-
ing presets. 
The proposed principles represent a
paradigm shift in microfluidic technol-
ogy in three important ways: 
• Microfluidic devices are to be directly
integrated with, onto, or around tissue
samples, in contrast to the conven-
tional method of off-chip sample ex-
traction followed by sample insertion
in microfluidic devices. 
• Architectural and operational princi-
ples of microfluidic devices are to be
subordinated to suit specific tissue
structure and needs, in contrast to the
conventional method of building de-
vices according to fluidic function
alone and without regard to tissue
structure. 
• Sample acquisition from tissue is to be
performed on-chip and is to be inte-
grated with the diagnostic measure-
ment within the same device, in con-
trast to the conventional method of
off-chip sample prep and subsequent
insertion into a diagnostic device. A
more advanced form of tissue integra-
tion with microfluidics is tissue encap-
sulation, wherein the sample is com-
pletely encapsulated within a
microfluidic device, to allow for full
surface access. 
The immediate applications of these
approaches lie with diagnostics of tissue
slices and biopsy samples — e.g. for can-
cer — but the approaches would also be
very useful in comparative genomics and
other areas of fundamental research in-
volving heterogeneous tissue samples. 
The approach advocates and utilizes
the bottom-up customization of mi-
crofluidic architectures to biosamples,
in contrast to the traditional top-down
approach of building the architectures
first and then putting the biosamples in-
side. Further, as particular embodiments
of the above principle, novel techniques
of sub-sample selection and isolation are
presented. These techniques would have
wide applicability in fundamental re-
search and biomedical diagnostics. 
In particular, an in situ microfluidic
technique of single-cell isolation, or
multiple single-cell isolations, is de-
scribed, and is performed upon tissue
sections attached to pathology glass
slides. The technique combines the ad-
vantages of preserving the architec-
tural integrity of the tissue section
while allowing flexibility and precision
of cell selection, rapid prototyping,
and enhanced sample purity, while
benefiting from the experience of the
pathologist in the selection process.
The result is a system that would allow
the rapid and reliable biochemical
analysis and diagnosis of pathologic
processes with sensitivity extended
down to the level of even a single cell,
with high levels of confidence in the di-
agnostic determination. 
These techniques would allow the ex-
traction of cells and cell nuclei chosen
for their potentially pathologic origin,
https://ntrs.nasa.gov/search.jsp?R=20120006648 2019-08-30T19:52:48+00:00Z
NASA Tech Briefs, August 2011 21
A process has been developed that can
confer novel properties, such as metal re-
sistance, to a host bacterium. This same
process can also be used to produce
RNAs and peptides that have novel prop-
erties, such as the ability to bind particu-
lar compounds. It is inherent in the
method that the peptide or RNA will be-
have as expected in the target organism.
Plasmid-born mini-gene libraries coding
for either a population of combinatorial
peptides or stable, artificial RNAs carry-
ing random inserts are produced. These
libraries, which have no bias towards any
biological function, are used to trans-
form the organism of interest and to
serve as an initial source of genetic varia-
tion for stress-driven evolution. 
The transformed bacteria are propa-
gated under selective pressure in order
to obtain variants with the desired prop-
erties. The process is highly distinct
from in vitro methods because the vari-
ants are selected in the context of the
cell while it is experiencing stress.
Hence, the selected peptide or RNA will,
by definition, work as expected in the
target cell as the cell adapts to its pres-
ence during the selection process. Once
the novel gene, which produces the
sought phenotype, is obtained, it can be
transferred to the main genome to in-
crease the genetic stability in the organ-
ism. Alternatively, the cell line can be
used to produce novel RNAs or peptides
with selectable properties in large quan-
tity for separate purposes. The system al-
lows for easy, large-scale purification of
the RNAs or peptide products.
Stress-Driven Selection of Novel Phenotypes
A methodology allows the experimental design of novel peptides and RNAs 
that have desired properties.
Lyndon B. Johnson Space Center, Houston, Texas
The aim of tissue engineering (TE) is
to restore tissue and organ functions
with minimal host rejection. TE is seen
as a future solution to solve the crisis of
donor organs for transplant, which faces
a shortage expected only to increase in
the future. In this innovation, a flexible
and configurable scaffold has been con-
ceived that mechanically stresses cells
that are seeded on it, stimulating them
to increased growth. 
The influence of mechanical stress/
loading on cell growth has been ob-
served on all forms of cells. For exam-
ple, for cartilages, studies in animals, tis-
sue explants, and engineered tissue
scaffolds have all shown that cartilage
cells (chondrocytes) modify their extra-
cellular matrix in response to loading.
The chondrocyte EMC production re-
sponse to dynamics of the physical envi-
ronment (in vivo cartilage develop-
ment) illustrates a clear benefit (better
growth) when stressed. It has been
shown that static and dynamic compres-
sion regulates PRG4 biosynthesis by car-
tilage explants. 
Mechanical tissue stimulation is bene-
ficial and (flexible) scaffolds with mov-
able components, which are able to in-
duce mechanical stimulation, offer
advantages over the fixed, rigid scaffold
design. In addition to improved cell
growth from physical/mechanical stimu-
lation, additional benefits include the
ability to increase in size while preserv-
ing shape, or changing shape.
By making scaffolds flexible, allowing
relative movement between their com-
ponents, adding sensing (e.g., for de-
tecting response of cells to drug release
and to mechanical actions), building
controls for drug release and move-
ment, and building even simple algo-
rithms for mapping sensing to action,
these structures can actually be made
into biocompatible and biodegradable
robots. Treating them as robots is a per-
spective shift that may offer advantages
in the design and exploitation of these
structures of the future.
This work was done by Adrian Stoica of Cal-
tech for NASA’s Jet Propulsion Laboratory. For
more information, contact iaoffice@jpl.nasa.gov.
This invention is owned by NASA, and a
patent application has been filed. Inquiries con-
cerning nonexclusive or exclusive license for its
commercial development should be addressed to
the Patent Counsel, NASA Management Of-
fice–JPL. Refer to NPO-47142.
Robotic Scaffolds for Tissue Engineering and Organ Growth 
Biocompatible and biodegradable smart scaffolds could reconfigure their shape and size to
accommodate organ development. 
NASA’s Jet Propulsion Laboratory, Pasadena, California 
e.g. cancer. The chief advantages of the
proposed methods are their speed, ease,
reliability, and capacity to select individ-
ual cells from a tissue slice population
with a higher degree of purity and speci-
ficity. The result is the extracted DNA
can be biochemically analyzed with a
higher degree of diagnostic accuracy, as
the isolated sub-sample would not be di-
luted by unwanted material from the
ambient tissue. In comparison to other
techniques, the proposed methods
would combine high specificity with
high speed. 
This work was done by Lawrence A. Wade
of Caltech and Emil P. Kartalov, Darryl Shi-
bata, and Clive Taylor of the University of
Southern California for NASA’s Jet Propulsion
Laboratory. Further information is contained
in a TSP (see page 1).
In accordance with Public Law 96-517,
the contractor has elected to retain title to this
invention. Inquiries concerning rights for its
commercial use should be addressed to:
Innovative Technology Assets Management
JPL
Mail Stop 202-233
4800 Oak Grove Drive
Pasadena, CA 91109-8099
E-mail: iaoffice@jpl.nasa.gov
Refer to NPO-47561, volume and number
of this NASA Tech Briefs issue, and the
page number.


Principles, Techniques, and Applications of Tissue Microfluidics

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