Microfabricated Multi-Frequency Particle Impedance Characterization System

Abstract

Wehave developed a microfabricated flow-through impedance characterization system capable of performing AC, multi-frequency measurements on cells and other particles. The sensor measures both the resistive and reactive impedance of passing particles, at rates of up to 100 particles per second. Its operational bandwidth approaches 10 MHz with a signal-tonoise ratio of approximately 40 dB. Partide impedance is measured at three or more frequencies simultaneously, enabling the derivation of multiple particle parameters. This constitutes an improvement to the well-established technique of DC particle sizing via the Coulter Principle. Human peripheral blood granulocyte radius, membrane capacitance, and cytoplasmic conductivity were measured (r = 4.1 f.!m, Cmem = 0.9 f.!F/cm 2 , O"int = 0.66 S/m) and were found to be consistent with published values.

Single cell dielectric spectroscopy

“…Although this method allows analysis of cell characteristics, it does not enable broad band multi-frequency analysis of cells. A multifrequency measurement system has been reported by Fuller et al [101], in which discrete mixers, filters and direct digital signal synthesis circuitry was employed. Using mixed digital and analogue application-specific integrated circuits (ASICs), the system can measure up to eight frequencies simultaneously.…”

“…One method, patented by Liu et al [102] is a pulsed-FFT measurement technique. However, Fuller et al [101] pointed out a drawback with this technique. Since the energy of the excitation signal is spread across a wide band of frequencies, rather than concentrated at a single measurement frequency, the signal-to-noise ratio of the system is much worse than a discrete frequency system.…”

Integrated Coulter counter based on 2-dimensional liquid aperture control

“…For many medical and scientific applications, the diameter of the Coulter aperture ranges from approximately 30 to 200 m. Because of the small dimensions involved, integrated circuit technology has been used to fabricate the Coulter aperture [2,3] and even complete integrated Coulter counters without [4][5][6] and with hydrodynamic focussing [3]. However, these devices still use a fixed Coulter aperture, thereby having to make the trade-off between sensitiv-ity and the chance of clogging: the smaller the aperture the higher the sensitivity, but the larger the chance of clogging.…”

High speed multi-frequency impedance analysis of single particles in a microfluidic cytometer using maximum length sequences

“…[1][2][3]9,10 The disadvantage of this approach is that scanning the frequency can take several seconds, therefore high speed multi-frequency analysis of moving particles is not possible. One solution involves probing the sample with multi-frequencies simultaneously, as reported by Fuller et al 11 These authors used discrete mixers, filters and direct digital signal synthesis circuits with mixed digital and analog application-specific integrated circuit (ASIC) to measure eight frequencies simultaneously. However, the system is complicated and requires a large amount of mixed-signal hardware.…”

“…12 However, the latter method suffers from the disadvantage that the energy of the excitation signal is spread across a wide band of frequencies rather than concentrated at the specific measurement frequency. 11 Since a short duration pulse cannot deliver enough energy into the system, the signal to noise ratio (SNR) of the pulse-FFT method is worse than the classical discrete frequency system. MLS is a pseudo-random binary sequence (PRBS) and exhibits a uniform power spectral density over a wide frequency band, similar to white noise.…”