Hydrodynamic Tweezers:  1. Noncontact Trapping of Single Cells Using Steady Streaming Microeddies

Abstract

A key need for dynamic single-cell measurements is the ability to gently position cells for repeated measurements without perturbing their behavior. We describe a new method that uses a gentle secondary flow to trap and suspend single cells, including motile cells, at predictable locations in 3-D. Trapped cells can be more dense or less dense than the surrounding medium. The cells are suspended without surface contact in one of four steady streaming eddies created by audible-frequency fluid oscillation (< or =1000 Hz) in a microchannel containing a single fixed cylinder (radius = 125 microm). Comparison of measured trap locations to computations of the eddy flow show that each trap is located near the eddy center, and the location is controlled via the oscillation frequency. We use the motile phytoplankton cell (Prorocentrum micans) to experimentally measure the trapping force, which is controlled via the oscillation amplitude. Trapping forces up to 30 pN are generated while exerting moderate shear stresses (shear stresses < or = 1.5 N/m2) on the trapped cell. The magnitude of this trapping force is comparable to that of optical tweezers or dielectrophoretic traps, without requiring an external field outside the physiological range for cells (the shear stresses are comparable to those found in arterial blood flow). The unique combination of predictable 3-D positioning, insensitivity to cell and medium properties, strong adjustable trapping forces, and a gentle fluid environment makes hydrodynamic tweezers a promising new option for noncontact trapping of single cells in suspension.

Hydrodynamic trap for single particles and cells

“…Over the past two decades, a diverse set of methods based on optical, 1 electrokinetic, 2,3 magnetic, 4,5 acoustic, 6 and hydrodynamic forces [7][8][9][10][11][12] has been developed to confine and manipulate microscale and nanoscale particles in aqueous solution through direct control of particle position and velocity. Overall, these methods have been used to investigate a widearray of physical and biological problems, and each method exhibits a clear set of advantages and limitations as tools for studying living cells and biological systems.…”

“…Hydrodynamic forces have been used in both contact-based 12 and noncontact [7][8][9][10][11] methods to confine and manipulate particles. Contact-based methods are efficient in trapping very large numbers of particles to form dynamic arrays for high-throughput studies, albeit with limited ability for fine-scale manipulation of single particles.…”

“…Noncontact methods currently rely on either stagnation point flows [7][8][9][10] or microeddies. 11 Particle confinement based on stagnation point flows can provide high resolution manipulation of single particles. However, previous work has mainly focused on trapping macroscopic ͑millimeter-sized͒ particles in aqueous solutions 7 or confinement of microscopic ͑micron-sized͒ particles in highly viscous solutions.…”

Exploitation of physical and chemical constraints for three-dimensional microtissue construction in microfluidics

“…We have reported a microfluidic 3D hepatocyte chip ͑Hepa Tox Chip͒ in which IC 50 values of five drugs calculated from the chip correlate well with the in vivo toxicity data. 42 The Hepa Tox Chip has eight parallel cell culture channels that are independently connected to outputs of a linear concentration gradient generator yielding eight different drug concentrations.…”

“…2͑d͔͒. Lutz et al 50 generated steady streams to trap cells by allowing oscillations ͑produced by an audible frequency of ϳ1000 Hz͒ inside a microchannel to interact with a fixed cylinder. In the microvortices, cells experience very low-shear stress ͑ϳ10 −2 N / m 2 ͒; the trapping efficiency is high; the trapping forces are adjustable; and the method is insensitive to the cell type or media properties.…”