TY - JOUR
T1 - Rapid Isolation and Concentration of Pathogenic Fungi Using Inertial Focusing on a Chip-Based Platform
AU - Fuchs, Beth Burgwyn
AU - Eatemadpour, Soraya
AU - Martel-Foley, Joseph M.
AU - Stott, Shannon
AU - Toner, Mehmet
AU - Mylonakis, Eleftherios
N1 - Funding Information:
BF received funding for this research from the Rhode Island Foundation and The Eppley Foundation for Research, and NIH award 1P20GM121344. This work was partially supported by NIH P41 (EB002503) Biotechnology Resource Center (MT). We appreciate the technical support that was provided by Octavio Hurtado and Sezgi Nuzumlali.
Publisher Copyright:
© Copyright © 2019 Fuchs, Eatemadpour, Martel-Foley, Stott, Toner and Mylonakis.
PY - 2019/2/12
Y1 - 2019/2/12
N2 - Systemic Candida infections remain a leading cause of nosocomial infections in the United States and worldwide. Many challenges remain in achieving rapid, direct diagnosis of fungal bloodstream infections due to limitations of conventional diagnostic methods that continue to demonstrate poor sensitivity, prolonged culture times that lead to delayed treatment, and detection variability between tests that compromises result reproducibility. Despite advancements in technology, mortality, and cost of care presented by blood stream infection with Candida spp. (candidemia) continues to rise and there is an urgent need for the development of novel methods to accurately detect Candida species present within the blood. This is especially true when patients are infected with drug resistant strains of Candida where accurate and immediate therapeutic treatment is of the importance. This study presents a method of separating fungal cells from lysed blood using inertial forces applied through microfluidics in order to abbreviate the time required to achieve a diagnosis by mitigating the need to grow blood cultures. We found that C. albicans can segregate into a focused stream distinct from white blood cells isolated within the Inertial Fungal Focuser (IFF) after red blood cell lysis. As a result of the focusing process, the collected cells are also concentrated 2.86 times. The same IFF device is applicable to non-albicans species: Candida parapsilosis, Candida glabrata, and Candida tropicalis, providing both isolation from lysed blood and a reduction in solution volume. Thus, the devised platform provides a means to isolate medically significant fungal cells from blood and concentrate the cells for further interrogation.
AB - Systemic Candida infections remain a leading cause of nosocomial infections in the United States and worldwide. Many challenges remain in achieving rapid, direct diagnosis of fungal bloodstream infections due to limitations of conventional diagnostic methods that continue to demonstrate poor sensitivity, prolonged culture times that lead to delayed treatment, and detection variability between tests that compromises result reproducibility. Despite advancements in technology, mortality, and cost of care presented by blood stream infection with Candida spp. (candidemia) continues to rise and there is an urgent need for the development of novel methods to accurately detect Candida species present within the blood. This is especially true when patients are infected with drug resistant strains of Candida where accurate and immediate therapeutic treatment is of the importance. This study presents a method of separating fungal cells from lysed blood using inertial forces applied through microfluidics in order to abbreviate the time required to achieve a diagnosis by mitigating the need to grow blood cultures. We found that C. albicans can segregate into a focused stream distinct from white blood cells isolated within the Inertial Fungal Focuser (IFF) after red blood cell lysis. As a result of the focusing process, the collected cells are also concentrated 2.86 times. The same IFF device is applicable to non-albicans species: Candida parapsilosis, Candida glabrata, and Candida tropicalis, providing both isolation from lysed blood and a reduction in solution volume. Thus, the devised platform provides a means to isolate medically significant fungal cells from blood and concentrate the cells for further interrogation.
KW - Candida
KW - IFF
KW - cell separation
KW - fungal diagnostics
KW - fungi
KW - inertial focusing
KW - microfluidics
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U2 - 10.3389/fcimb.2019.00027
DO - 10.3389/fcimb.2019.00027
M3 - Article
C2 - 30809512
AN - SCOPUS:85073684015
SN - 2235-2988
VL - 9
JO - Frontiers in cellular and infection microbiology
JF - Frontiers in cellular and infection microbiology
M1 - 27
ER -