Review article examines how microfluidic analysis of whole blood could improve cancer cell detection
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Blood is a rich source of diagnostic information, but analyzing untreated whole blood in microfluidic devices remains technically challenging. A review article by UIC researchers examines those challenges and identifies opportunities to improve the isolation of rare cells, including circulating tumor cells.
Whole blood is difficult to move through microscale channels because its many cells and proteins can disrupt flow, clog devices, or undergo unintended changes during processing. In the review, researchers from UIC’s Richard and Loan Hill Department of Biomedical Engineering evaluate the advantages, challenges, and future directions of blood microfluidics. Blood microfluidics uses microscale channels to manipulate small blood samples for rapid diagnostics and cellular analysis. Many researchers use diluted or preprocessed blood because it is easier to work with than untreated whole blood.
Richard and Loan Hill Professor Ian Papautsky and BME doctoral student Sana Sheybanikashani recently published their invited review in Lab on a Chip.
The article examines key aspects of working with whole blood in microfluidic devices, including blood components, how the cells and blood components interact within the devices, and how investigators work with blood on chips, including animal blood. It also assesses where the field is in terms of how researchers are working with whole blood on microfluidic devices.
Sheybanikashani said that the review became broader in scope during the writing process. The article synthesizes published research on whole blood preparation and processing, compares commonly used techniques, identifies unresolved challenges, and outlines future directions for the field.
After realizing that researchers in the blood microfluidics space more often work with diluted blood than whole blood, Sheybanikashani and Papautsky were motivated to investigate how devices could analyze whole blood more directly. They hope this work will help streamline the process of liquid biopsy, taking a blood draw directly from a patient to a chip for analysis.
Circulating tumor cells, or CTCs, are cancer cells that are shed from primary or metastatic tumors into the bloodstream. Their presence and characteristics can provide information about disease progression, treatment response, and the risk of recurrence. The two researchers are looking into the streamlined process because the standard diluted blood process not only takes extra time because of additional processing, but can also damage the CTCs because they’re very rare and fragile.
Papautsky’s previous work on separation of pancreatic CTCs from healthy blood cells shaped the approach he and Sheybanikashani took while approaching the review article.
“Based on Sheybanikashani’s now extensive knowledge of how to work with blood microfluidic devices, she’s working to improve our device designs for CTC isolation,” Papautsky said.
“Our devices are not optimized for detecting intact CTC clusters because they are larger and can dissociate during processing,” Sheybanikashani said. “We’re developing better approaches to ensure these clusters remain intact to later separate and analyze them.”
So that would also affect how these different techniques can change the outcomes of microfluidic isolation.
Papautsky and Sheybanikashani are working on isolation of CTC clusters in clinical samples. Conventional sample preparation may involve RBC lysis, blood dilution, and additional handling steps before CTC clusters can be isolated for downstream analysis. She added that from a lab perspective, if the CTCs remain intact, using them for downstream analyses would aid researchers in looking at patient or tumor status in future research.
“Part of my PhD project focuses on separating CTCs in blood samples,” Sheybanikashani said. “My current research is based on the isolation of CTCs in clusters, which are highly metastatic, where previous research focused on single CTCs.”
Previous studies suggest that CTC clusters may have substantially greater metastatic potential than individual CTCs.