Electric impedance microflow cytometry for characterization of cell disease states.
The electrical properties of biological cells have connections to their pathological states. Here we present an electric impedance microflow cytometry (EIMC) platform for the characterization of disease states of single cells. This platform entails a microfluidic device for a label-free and non-invasive cell-counting assay through electric impedance sensing. We identified a dimensionless offset parameter δ obtained as a linear combination of a normalized phase shift and a normalized magnitude shift in electric impedance to differentiate cells on the basis of their pathological states. This paper discusses a representative case study on red blood cells (RBCs) invaded by the malaria parasite Plasmodium falciparum. Invasion by P. falciparum induces physical and biochemical changes on the host cells throughout a 48-h multi-stage life cycle within the RBC. As a consequence, it also induces progressive changes in electrical properties of the host cells. We demonstrate that the EIMC system in combination with data analysis involving the new offset parameter allows differentiation of P. falciparum infected RBCs from uninfected RBCs as well as among different P. falciparum intraerythrocytic asexual stages including the ring stage. The representative results provided here also point to the potential of the proposed experimental and analysis platform as a valuable tool for non-invasive diagnostics of a wide variety of disease states and for cell separation.
Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
E
E
Du
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Sungjae
S
Ha
Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Monica
M
Diez-Silva
Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Ming
M
Dao
Department of Materials Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Subra
S
Suresh
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Anantha P
AP
Chandrakasan
D017097:Electric Impedance; D004912:Erythrocytes / Q000166:cytology* / Q000469:parasitology*; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D010963:Plasmodium falciparum / Q000502:physiology