Magnetic separation of acoustically focused cancer cells from blood for magnetographic templating and analysis

Abstract

Liquid biopsies hold enormous promise for the next generation of medical diagnoses. At the forefront of this effort, many are seeking to capture, enumerate and analyze circulating tumor cells (CTCs) as a means to prognosticate and develop individualized treatments for cancer. Capturing these rare cells, however, represents a major engineering challenge due to their low abundance, morphology and heterogeneity. A variety of microfluidic tools have been developed to isolate CTCs from drawn blood samples; however, few of these approaches offer a means to separate and analyze cells in an integrated system. We have developed a microfluidic platform comprised of three modules that offers high throughput separation of cancer cells from blood and on-chip organization of those cells for streamlined analyses. The first module uses an acoustic standing wave to rapidly align cells in a contact-free manner. The second module then separates magnetically labeled cells from unlabeled cells, offering purities exceeding 85% for cells and 90% for binary mixtures of synthetic particles. Finally, the third module contains a spatially periodic array of microwells with underlying micromagnets to capture individual cells for on-chip analyses (e.g., staining, imaging and quantification). This array is capable of capturing with accuracies exceeding 80% for magnetically labeled cells and 95% for magnetic particles. Overall, by virtue of its holistic processing of complex biological samples, this system has promise for the isolation and evaluation of rare cancer cells and can be readily extended to address a variety of applications across single cell biology and immunology.

An integrated enrichment system to facilitate isolation and molecular characterization of single cancer cells from whole blood

“…Our enrichment system in-line with a sorter uses magnetic depletion and acoustic cell separation technologies to enrich for rare cancer cells in a one-step process. This confirms our integrated rare cell enrichment and isolation system is suitable for isolation of CTCs that are variable in size (10,(30)(31)(32). Others have shown this approach to be useful in clinical studies isolating and characterizing rare cells (27)(28)(29).…”

“…S4). This confirms our integrated rare cell enrichment and isolation system is suitable for isolation of CTCs that are variable in size (10,(30)(31)(32). By combining the two technologies we are able to simplify the enrichment process for cell sorting and demonstrate a higher cancer cell recovery rate compared with traditional enrichment processes (Fig.…”

Advances in Magnetic Nanoparticles for Biomedical Applications

“…The last module integrates an array of microwells with underlying micromagnets to capture individual cells for on‐chip analysis. The high capture efficiency of 80% of magnetically labeled cells demonstrates the potential of this system not just for the isolation and evaluation of rare cancer cells, as it can be readily extended to address a variety of applications across single cell biology and immunology . Extensive reviews of the latest advances in microfluidic rare cell separation and processing can be found in refs.…”

Recent Advances and Future Perspectives on Microfluidic Liquid Handling

“…The effect of parameters, such as acoustic energy density and initial vertical location, on the displacement of microparticles were examined with this model. Shields et al [ 75 ] designed a multi-stage microfluidic platform for separation of cancer cells from blood. In the first module, the acoustic standing wave is exploited for immediate alignment of cells.…”