Researchers Devise 3D Printing Method for Cost-Effective Preparation of Biochips

Microfluidics is the backbone of important research in clinical diagnostics, drug discovery, health care, and medicine. However, in the area of biology, 3D printed microfluidics platforms, which are essentially small-scale plumbing systems on a chip, have helped researchers understand and analyze sensitive bioanalytical systems.

There is currently a great need to be able to reduce the feature diameters in biological arrays, which would in turn increase how many probes are on the surface. However, high-energy beams are necessary for most nanolithography methods, which can denature or destroy soft matter.

A team of researchers from the Advanced Science Research Center (ASRC) at the Graduate Center of the City University of New York (CUNY) have been studying how 3D printing and microfluidics can be combined to develop a more cost-effective, efficient way to prepare microarrays, or biochips, which screen for and analyze biological changes in bioterrorism agents, disease development, and research involving biological components.

CUNY, the public university system of New York City, is the largest urban university in the US. Last month, a collaborative team of researchers from the university’s ASRC Nanoscience Initiative, the Beacon School, and Hunter College, published a paper, titled “Massively Multiplexed Tip-Based Photochemical Lithography under Continuous Capillary Flow,” in the Chem journal.

The paper’s summary reads, “Multiplexed microarrays—where different biological probes are spatially encoded onto a surface into spots with micrometer-scale diameters—have facilitated the rapid advancement of ‘omics’ research. Further miniaturization of feature diameters could increase the number of probes in a microarray, reduce the sample required for analysis, and decrease costs. Tip-based lithography (TBL) has gained popularity for patterning delicate, biologically active materials, but no versatile TBL-based multiplexing strategy has been devised. Here, we combine microfluidics, beam pen lithography, and photochemical surface reactions to create multiplexed arrays. For proof of concept, the thiol-ene reaction was optimized, and the reaction kinetics were analyzed. Subsequently, we created several patterns containing multiple fluorescent alkenes, where each pattern was designed to demonstrate a different capability of this instrument. This patterning strategy is a powerful approach to studying and optimizing organic reactions on surfaces and creating massively multiplexed arrays and, as such, could provide an entirely new approach for miniaturizing biochips or understanding interfacial reactivity.”

Arrays of nanoscopic tips are used in TBL technology to pattern reagents on a surface without causing any harm, but there isn’t a versatile multiplexing strategy. In the paper, the researchers explain how they developed a new biochip 3D printing technique by combining microfluidics, beam-pen, or tip-based, lithography, and photochemical surface reactions.

Adam Braunschweig

“This is essentially a new nanoscale printer that allows us to imprint more complexity on the surface of biochip than any of the currently available commercial technologies. It will help us to gain much better understanding of how cells and biological pathways work,” said Adam Braunschweig, lead researcher and associate professor with the Nanoscience Initiative.

In the team’s new method, a biochip’s surface is first exposed to specific organic reagents. Then, the immobilized reagents are forced to adhere to the biochip’s surface by a tightly focused beam of light. In doing so, scientists are able to expose one chip multiple times to the same, or different, factors, and imprint the resulting reactions onto different sections of the chip. This leads to a biochip which is able to, according to CUNY, “accommodate more probes than is achievable with current commercial platforms.”

Now, the research team is looking to fine-tune its new 3D printing biochip approach.

ASRC Research Associate Carlos Carbonell, the paper’s lead author, explained, “We want to be able to record even more complex surface interactions and reduce our resolution down to a single molecule. This technique gives rise to a new method of microarray creation that should be useful to the entire field of biological ‘omics’ research.”

Applications for the team’s 3D printing platform include preparing gene, glycan, and protein chips that can advance amics research, in addition to having developed, according to the paper, “a new tool for probing interfacial reactivity.”

The tool helps researchers reliably 3D print on the length scale of biological interactions on multiple delicate materials, like metals, lipids, and glasses, without having to set foot in a clean room. Scientists can also lower the cost of biochip-facilitated research by fitting more reactive probes onto single chips.

Co-authors of the paper include Carbonell, Daniel J. Valles, Alexa M. Wong, Mei Wai Tsui, Moussa Niang, and Braunschweig.

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[Source/: Tech Xplore / Images: CUNY]