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Published on: July 18, 2012
Enhanced Molecular Diagnosis of Bloodstream Candida Infection with Size-Based Inertial Sorting at Submicron
Xiaoguang Lu1, Joycelyn Jia Ming Chow1, Seok Hwee Koo2
1Pillar of Engineering Product Development, Singapore University of Technology and Design, 487372 Singapore.
Abstract:
Inertial microfluidics has been proven to be a powerful tool for high-throughput, size-based cell sorting in diverse biomedical applications. In the case of Candida-related sepsis, Candida species and major blood cells (i.e., red blood cells and white blood cells) have a size distribution of 3-5 and 6-30 μm, respectively. To effectively retrieve a majority of Candida species and remove most of the interfering blood cells for accurate molecular analysis, inertial sorting of micron-sized biological particles with submicron size difference is highly desired, but far unexplored till now. In this work, we present a new channel design for an inertial microfluidic sorting device by embedding microsquares to construct periodic contractions along a series of repeating curved units. This unique channel design allows us to enhance inertial lift force at the microsquare zone and produce localized secondary Dean flow drag force in addition to global Dean flow drag force. This inertial sorting device has successfully separated 5.5 μm particles from 6.0 μm particles with a recovery ratio higher than 80% and a purity higher than 92%, demonstrating a size-based inertial sorting at submicron resolution (i.e., 0.5 μm). We further applied this inertial sorting device to purify Candida species from whole blood sample for enhanced molecular diagnosis of bloodstream Candida infection and especially compared it with the commonly used lysis-centrifugation-based purification method (STEM method) by recovering two species of Candida (Cornus glabrata and Candida albicans) from Candida-spiked blood samples. Through quantitative polymerase chain reaction (qPCR) analysis, we found that our inertial sorting approach has nearly 3-fold improvement on the pathogen recovery than the STEM method at pathogen abundances of 103 cfu/mL and 102 cfu/mL. The present inertial sorting at submicron resolution provides a simple, rapid, and efficient pathogen purification method for significantly improved molecular diagnosis of bloodstream Candida infection.
Insights
This study introduces a novel inertial microfluidic device for precise separation of micron-sized particles, crucial for diagnosing Candida infections. The new design achieves high purity and recovery, outperforming traditional methods for Candida purification from blood samples.
Area of Science:
- Biomedical Engineering
- Microfluidics
- Cell Sorting
- Infectious Disease Diagnostics
Background:
- Inertial microfluidics enables high-throughput, size-based cell sorting for biomedical applications.
- Accurate diagnosis of *Candida*-related sepsis requires separating small *Candida* species (3-5 μm) from larger blood cells (6-30 μm).
- Submicron resolution inertial sorting for separating particles with minimal size differences remains largely unexplored.
Purpose of the Study:
- To develop and validate a novel inertial microfluidic sorting device capable of submicron particle resolution.
- To enhance pathogen purification for improved molecular diagnosis of bloodstream *Candida* infections.
- To compare the efficacy of the developed device against the lysis-centrifugation-based STEM method.
Main Methods:
- A new microfluidic channel design featuring embedded microsquares was engineered to enhance inertial lift and Dean flow drag forces.
- The device's ability to separate particles with submicron size differences was tested using 5.5 μm and 6.0 μm particles.
- The inertial sorting device was applied to purify *Candida* species (*Cornus glabrata*, *Candida albicans*) from spiked whole blood samples.
Main Results:
- Successful separation of 5.5 μm particles from 6.0 μm particles with >80% recovery and >92% purity, demonstrating submicron resolution (0.5 μm).
- The inertial sorting approach achieved nearly a 3-fold improvement in pathogen recovery compared to the STEM method at low *Candida* abundances (10³ and 10² cfu/mL).
- Quantitative polymerase chain reaction (qPCR) analysis confirmed enhanced molecular diagnosis of *Candida* from purified samples.
Conclusions:
- The novel inertial microfluidic device offers high-precision, submicron-resolution particle sorting.
- This method provides a simple, rapid, and efficient approach for purifying *Candida* from blood, significantly improving molecular diagnostic accuracy.
- The developed technology holds promise for enhanced diagnosis and management of bloodstream *Candida* infections.
