Office of Technology Transfer – University of Michigan

Label-Free High Throughput Microfluidic Device for Size-Based Separation of Cells

Technology #5558

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Researchers
Sunitha Nagrath
Managed By
Kristen Wolff
Senior Licensing Specialist, Medical Devices 734-647-5604
Patent Protection
US Patent Pending

Circulating tumor cells (CTCs) are small, rare cells that have shed from a primary tumor and circulate in the bloodstream. CTCs can cause subsequent growth of additional tumors (metastasis) in other organs, which has been found to trigger a mechanism that is responsible for many cancer-related deaths. Cancer research has demonstrated that CTCs derive from clones in the primary tumor, and recently it has been demonstrated that these circulating tumor cells reflect molecular features of cells within tumor masses. Therefore, CTCs are essentially a “liquid biopsy” which reveals metastasis in action and provides important information about a patient’s disease status. Proper analysis of CTCs from blood samples could be an invaluable tool for early stage detection of cancer as well as recurrence monitoring. The biomarkers market was valued at $3.5 billion in 2004 and increased to $13 billion in 2011 at a Compound Annual Growth Rate (CAGR) of 20.1%. The majority of revenue is generated through the application of biomarkers in the discovery, testing and prescription of oncology therapeutics, making it one of the biggest therapeutic areas.

The present challenge lies in the detection of rare cells such as CTCs. CTCs tend to only be present in an amount of 1 CTC per 1 billion blood cells. Many current strategies for isolating CTCs are limited to complex analytic approaches that are typically very low yield and low purity which affects the sensitivity and accuracy of detection. Many existing technologies rely on size based separation techniques since CTCs from solid tumors tend to be larger in size compared to typical red blood cells. These methods usually pass CTCs through pores etched in membranes in order to trap the CTCs on the membrane. However, these techniques tend to suffer from clogging of pores and pressure drops in devices that include such membranes due to the buildup of cells on the membrane. Other technologies that use antibody-based capture have difficulty in retrieving live cells for downstream analysis. These methods are time-consuming for both preparation and sample processing, and also suffer from low throughput, which hinder its utilization in clinic.

Label-free high throughput microfluidic device for size-based separation of cells

This solution comprises a microfluidic device and novel separation technique to isolate rare cells such as CTCs from liquid. The microfluidic device uses an inlet for receiving the fluid sample, a labyrinth channel structure in fluid communication with the inlet, and an outlet in fluid communication with the labyrinth channel structure for collecting the rare cells separated from the other cells in the fluid sample. The labyrinth considers cell-specific flow rate as well as the wall curvature in order to leverage inertial and drag forces to move selected particles from the center into directed outlets specific for size, thus capturing the desired CTCs.

Applications

• Separation of rare cells from liquid media
• Isolation and detection of CTCs from the blood stream

Advantages

• High throughput (2mL / min)
• High recovery and specificity
• Label-free (non immune-affinity based)