Integrative Magneto-Microfluidic Separation of Immune Cells Facilitates Clinical Functional Assays
Hee Sik Shin1, Jeehun Park2, Seung Yeop Lee3
1Department of Electrical Engineering, Hanyang University, Seoul, 04763, Republic of Korea.
Insights
A novel magneto-microfluidic chip rapidly isolates natural killer (NK) cells from whole blood. This technology simplifies immune cell analysis for improved clinical diagnosis and disease monitoring.
Area of Science:
- Immunology
- Microfluidics
- Biomedical Engineering
Background:
- Analyzing natural killer (NK) cell function is crucial for clinical diagnosis but is complicated by their interaction with other immune cells.
- Existing methods require complex sample preparation, including cell isolation, red blood cell (RBC) removal, and buffer exchange.
Purpose of the Study:
- To develop an integrated, self-powered magneto-microfluidic cell separation (SMS) chip for rapid and high-purity isolation of NK cells.
- To streamline sample preparation for downstream functional analysis of NK cells.
Main Methods:
- The SMS chip utilizes an iron sphere-filled reservoir to intensify magnetic field gradients for immuno-magnetic cell selection.
- Size-selective separation via a microfluidic lattice removes excess RBCs and performs buffer exchange.
- Self-powered microfluidic pumping enables rapid NK cell isolation within 40 minutes.
Main Results:
- The SMS chip successfully isolated high-purity NK cells from whole blood samples.
- The isolated NK cells were analyzed for functional activities, revealing potential abnormalities in hepatocellular cancer patients.
- The chip demonstrated ease of use, rapid sorting, and minimal blood volume requirements.
Conclusions:
- The developed SMS chip offers a simplified, rapid, and efficient method for NK cell isolation and functional analysis.
- This technology has the potential to facilitate cell-based diagnostics by enabling the use of immune cell subtypes.
- The SMS chip can aid in identifying immune cell functional abnormalities for improved disease diagnosis and monitoring.
Abstract:
Accurately analyzing the functional activities of natural killer (NK) cells in clinical diagnosis remains challenging due to their coupling with other immune effectors. To address this, an integrated immune cell separator is required, which necessitates a streamlined sample preparation workflow including immunological cell isolation, removal of excess red blood cells (RBCs), and buffer exchange for downstream analysis. Here, a self-powered integrated magneto-microfluidic cell separation (SMS) chip is presented, which outputs high-purity target immune cells by simply inputting whole blood. The SMS chip intensifies the magnetic field gradient using an iron sphere-filled inlet reservoir for high-performance immuno-magnetic cell selection and separates target cells size-selectively using a microfluidic lattice for RBC removal and buffer exchange. In addition, the chip incorporates self-powered microfluidic pumping through a degassed polydimethylsiloxane chip, enabling the rapid isolation of NK cells at the place of blood collection within 40 min. This chip is used to isolate NK cells from whole blood samples of hepatocellular cancer patients and healthy volunteers and examined their functional activities to identify potential abnormalities in NK cell function. The SMS chip is simple to use, rapid to sort, and requires small blood volumes, thus facilitating the use of immune cell subtypes for cell-based diagnosis.


