Abstract
We present the first in-depth system integration study of in-plane hydrodynamic focusing in a microfluidic impedance cytometry lab-on-a-chip. The method relies on constricting the detection volume with non-conductive sheath flows and characterizing particles or cells based on changes in impedance. This approach represents an avenue of overcoming current limitations in sensitivity with translating cytometers to the point of care for rapid, low-cost blood analysis. While examples of integrated devices are present in the literature, no systematic study of the interplay between hydrodynamics and electrodynamics has been carried out as of yet. We develop analytical and numerical models to describe the impedimetric response of the sensor as a function of cellular characteristics, physical flow properties, and device geometry. We fabricate a working prototype lab-on-a-chip for experimental validation using latex particles. We find that ionic diffusion can be a critical limiting factor even at high Péclet number. Moreover, we explore geometric variations, revealing that the ionic diffusion-related distance between the center of the hydrodynamic focusing junction and the impedance measurement electrodes plays a dominant role. With our device, we demonstrate over fivefold enhancement in impedance signals and population separation with in-plane hydrodynamic focusing. It is only through such in-depth system studies, in both models and experiments, that optimal utilization of microsystem capabilities becomes possible.
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Abbreviations
- ⌀ (µm):
-
Cell diameter
- VA (µm):
-
Virtual aperture width
- Q s, Q f (µl/h):
-
Flow rates of sample and focus streams
- FR (1):
-
Flow ratio (sample flow over total flow)
- Z, Z empty (Ω):
-
Impedance, empty channel impedance
- |ΔZ| (%):
-
Relative change in impedance (impedance signal)
- Δ|ΔZ| (%):
-
Population separation
- δ (%):
-
Population spread
- w, w fc (µm):
-
Center (sample) and focus channel width
- h (µm):
-
Channel height
- l, g (µm):
-
Microelectrode length and gap
- d (µm):
-
Distance from focus junction to electrode
- med, el, DI, ion, cell, mem, cyt :
-
Subscripts denoting: medium, electrolyte component of medium, DI water component of medium, ions in the medium, cells in the medium, membrane component of cell, cytosol component of cell
- P, V (µm3):
-
Particle and electrical interaction volume
- Π (1):
-
Volume fraction of particle in electrical interaction volume
- σ (S/m):
-
Conductivity
- ε (F/m):
-
Permittivity
- C (1):
-
Normalized concentration
- IS (M):
-
Ionic strength
- λ D (µm):
-
Debye length
- C offset, C amp (1):
-
Concentration profile fit parameters
- s p, s s (µm):
-
Concentration profile fit parameters
- f, f s (Hz):
-
Signal and sampling frequency
- Pe, Re (1):
-
Péclet number, Reynolds number
- RMSE (%):
-
Root-mean-square error
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Acknowledgments
The authors would like to thank the Robert W. Deutsch Foundation and the Maryland Innovation Initiative for financial support. The authors also appreciate the support of the Maryland NanoCenter and its FabLab. The authors wish to thank Robert Dietrich for useful discussions.
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This research was performed while H. Ben-Yoav was at the MEMS Sensors and Actuators Laboratory (MSAL), Institute for Systems Research, Department of Electrical and Computer Engineering, University of Maryland, College Park, MD 20742, USA.
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Winkler, T.E., Ben-Yoav, H. & Ghodssi, R. Hydrodynamic focusing for microfluidic impedance cytometry: a system integration study. Microfluid Nanofluid 20, 134 (2016). https://doi.org/10.1007/s10404-016-1798-y
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DOI: https://doi.org/10.1007/s10404-016-1798-y