New York Genome Center Researchers Create Low-Cost Open Source 3D Printed Device for Single-Cell Analysis

So many of the benefits of 3D printing—and often all of them—allow for innovative strides to be made in a variety of industries today. Some of the most undeniable and significant impacts are being made in the medical field though, as researchers and manufacturers become more interested in manipulating the 3D realm to bioprint, create laboratory and medical devices, and more. As researchers continue to delve deeper on the cellular level, they also continue to become more successful in improving the quality of lives for patients around the world, including work with microfluidic devices.

Now, researchers at both the New York Genome Center (NYGC) and New York University (NYU) have developed a method for more affordable, widespread single-cell analysis, with the creation of a 3D printed microfluidic controller. This portable device, about the size of a tissue box, has already been used to study individuals with rheumatoid arthritis (RA) at the Hospital for Special Surgery (HSS), a leader in RA research and treatment.

“Most commercial microfluidic instruments are very costly; as a result, not every lab has access to exciting technology for single-cell analysis. We designed the instrument to perform droplet microfluidics and in particular Drop-seq, a massively parallel technology for single cell RNA-sequencing,” said William Stephenson PhD, Senior Research Engineer in the NYGC’s Technology Innovation Lab, who led the development of the instrument and is a lead author on the study.

The study, along with an explanation regarding the new device, is outlined fully in a recently published paper, ‘Single-cell RNA-seq of rheumatoid arthritis synovial tissue using low-cost microfluidic instrumentation.’ The researchers were able to sequence a total of 20,387 single cells, resulting in 13 transcriptomically distinct clusters.

“This dataset gave us the opportunity to identify individual subpopulations of cells that could drive the progression of RA, even if they have not been previously characterized,” said Rahul Satija PhD, a Core Faculty Member at NYGC, Assistant Professor of Biology at NYU, and senior author on the study.

The device is not only simple to use but is open source and will work in a range of different experiments using droplet microfluidics.

“The instrument is comprised of electronic and pneumatic components affixed to a 3D printed frame. The entire system is operated through software control using a graphical user interface on a touchscreen. Requiring only a standard wall power outlet, the instrument has an extremely small footprint; small enough to fit on a bench top or in a biocontainment hood,” state the researchers in their paper.

“The total cost of materials to construct an instrument is approximately $575. This represents an approximately 20-fold and 200-fold reduction in cost compared to a research-level, syringe-pump based microfluidic setup, and a commercial microfluidic platform, respectively.”

During the study, the scientists were particularly fascinated by how different the gene expression patterns were displayed in the 13 groups.

“Roughly an hour after surgical excision, individual cells from patient tissues were labeled for single-cell sequencing. From this work, we have classified unrecognized fibroblast subtypes that may prove to be important drug targets for our RA patients,” said Laura Donlin, Co-Director of the HSS Precision Medicine Lab and Assistant Professor at Weill Cornell Medicine, and a lead author on the study.

With flow cytometry, the team was able to confirm the existence of these new groups, along with realizing that they exhibited ‘distinct localization patterns’ with the joint tissue in RA patients.

As the researchers continue to work on creating a full cell atlas for synovial tissue, they also plan to:

• Collect data from other patients suffering from rheumatoid arthritis
• Explore samples displaying conditions like psoriatic arthritis and osteoarthritis
• Use a specialized technique (CITE-seq) to classify cell types by evaluationg surface proteins
• Examine samples such as those indicating infectious disease—taking on research that would be more difficult in a standard lab

“We hope that this instrument lowers the hurdles associated with performing single-cell transcriptome profiling experiments in basic research and clinical settings,” Dr. Stephenson said.

NYGC is a non-profit learning and research institution focused on both biomedical research and clinical care. The goal of the work produced at NYGC is ultimately to use genomic research for creating improved diagnostics, therapeutics, and treatments for diseases found in the human race. Read more about NYGC here.

Further instructions regarding the controller can be found here, along with assembly manuals. Study authors included William Stephenson, Laura T. Donlin, Andrew Butler, Cristina Rozo, Bernadette Bracken, Ali Rashidfarrokhi, Susan M. Goodman, Lionel B. Ivashkiv, Vivian P. Bykerk, Dana E. Orange, Robert B. Darnell, Harold P. Swerdlow and Rahul Satija.

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