Researchers have invented a technique that uses inexpensive paper to make “microfluidic” devices for rapid medical diagnostics and chemical analysis. To demonstrate the new concept, the researchers created paper strips containing arrays of dots dipped in luminol, a chemical that turns fluorescent blue when exposed to blood. Blood was then sprayed on the strips, showing the presence of hemoglobin. (Birck Nanotechnology Center, Purdue University) |
Researchers
have invented a technique that uses inexpensive paper to make
“microfluidic” devices for rapid medical diagnostics and chemical
analysis.
The
innovation represents a way to enhance commercially available
diagnostic devices that use paper-strip assays like those that test for
diabetes and pregnancy.
“With
current systems that use paper test strips you can measure things like
pH or blood sugar, but you can’t perform more complex chemical assays,”
said Babak Ziaie,
a Purdue University professor of electrical and computer engineering
and biomedical engineering. “This new approach offers the potential to
extend the inexpensive paper-based systems so that they are able to do
more complicated multiple analyses on the same piece of paper. It’s a
generic platform that can be used for a variety of applications.”
Findings are detailed in a research paper published online this week in the journal Lab on a Chip.
Current
lab-on-a-chip technology is relatively expensive because chips must be
specifically designed to perform certain types of chemical analyses,
with channels created in glass or plastic and tiny pumps and valves
directing the flow of fluids for testing.
The
chips are being used for various applications in medicine and research,
measuring specific types of cells and molecules in a patient’s blood,
monitoring microorganisms in the environment and in foods, and
separating biological molecules for laboratory analyses. But the chips,
which are roughly palm-size or smaller, are difficult to design and
manufacture.
The
new technique is simpler because the testing platform will be contained
on a disposable paper strip containing patterns created by a laser. The
researchers start with paper having a hydrophobic – or water-repellant –
coating, such as parchment paper or wax paper used for cooking.
“We
can buy this paper at any large discount retail store,” Ziaie said.
“These patterns can be churned out in the millions at very low cost.”
A
laser is used to burn off the hydrophobic coatings in lines, dots and
patterns, exposing the underlying water-absorbing paper only where the
patterns are formed.
“Since
the hydrophobic agent is already present throughout the thickness of
the paper, our method creates islands of hydrophilic patterns,” Ziaie
said. “This modified surface has a highly porous structure, which helps
to trap and localize chemical and biological aqueous reagents for
analysis. Furthermore, we’ve selectively deposited silica microparticles
on patterned areas to allow diffusion from one end of a channel to the
other.”
Those
microparticles help to wick liquid to a location where it would combine
with another chemical, called a reactant, causing it to change colors
and indicating a positive or negative test result.
Having
a patterned hydrophilic surface is needed for many detection methods in
biochemistry, such as enzyme-linked immunosorbent assay, or ELISA, used
in immunology to detect the presence of an antibody or an antigen in a
sample, Ziaie said.
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To
demonstrate the new concept, the researchers created paper strips
containing arrays of dots dipped in luminol, a chemical that turns
fluorescent blue when exposed to blood.
“Then
we sprayed blood on the strips, showing the presence of hemoglobin,”
said Ziaie, whose research is based at the Birck Nanotechnology Center
in the university’s Discovery Park. “This is just a proof of concept.”
Laser
modification is known to alter the “wettability” of materials by
causing structural and chemical changes to surfaces. However, this
treatment has never before been done on paper, he said.
The
researchers performed high-resolution imaging and spectroscopic
analysis to study the mechanism behind the hydrophobic-hydrophilic
conversion of laser-treated parchment paper.
The new approach is within a research area called paper microfluidics.
“Other techniques in paper microfluidics are more complicated,” Ziaie said.
For
example, other researchers have developed a method that lays down lines
of wax or other hydrophobic material on top of untreated, hydrophilic
paper.
“Our
process is much easier because we just use a laser to create patterns
on paper you can purchase commercially and it is already impregnated
with hydrophobic material,” Ziaie said. “It’s a one-step process that
could be used to manufacture an inexpensive diagnostic tool for the
developing world where people can’t afford more expensive analytical
technologies.”
The
strips might be treated with chemicals that cause color changes when
exposed to a liquid sample, with different portions of the pattern
revealing specific details about the content of the sample. One strip
could be used to conduct dozens of tests, he said.
The
strips might be inserted into an electronic reader, similar to
technology used in conventional glucose testers. Color changes would
indicate the presence or absence of specific chemical compounds.
The
research paper was written by graduate students Girish Chitnis, Zhenwen
Ding and Chun-Li Chang; Cagri A. Savran, an associate professor of
mechanical engineering, biomedical engineering and electrical and
computer engineering; and Ziaie.
The
National Science Foundation funded the work. The researchers have
patented the technique and it is available for licensing through the
Purdue Research Foundation Office of Technology Commercialization (http://www.prf.org/otc).
