Abstract

This paper develops a dielectrophoretic (DEP) chip with multi-layer electrodes and a micro-cavity array for programmable manipulations of cells and impedance measurement. The DEP chip consists of an ITO top electrode, flow chamber, middle electrode on an SU-8 surface, micro-cavity arrays of SU-8 and distributed electrodes at the bottom of the micro-cavity. Impedance sensing of single cells could be performed as follows: firstly, cells were trapped in a micro-cavity array by negative DEP force provided by top and middle electrodes; then, the impedance measurement for discrimination of different stage of bladder cancer cells was accomplished by the middle and bottom electrodes. After impedance sensing, the individual releasing of trapped cells was achieved by negative DEP force using the top and bottom electrodes in order to collect the identified cells once more. Both cell manipulations and impedance measurement had been integrated within a system controlled by a PC-based LabVIEW program. In the experiments, two different stages of bladder cancer cell lines (grade III: T24 and grade II: TSGH8301) were utilized for the demonstration of programmable manipulation and impedance sensing; as the results show, the lower-grade bladder cancer cells (TSGH8301) possess higher impedance than the higher-grade ones (T24). In general, the multi-step manipulations of cells can be easily programmed by controlling the electrical signal in our design, which provides an excellent platform technology for lab-on-a-chip (LOC) or a micro-total-analysis-system (Micro TAS).

Highlights

  • Bladder cancer is reported as the fourth most common type of cancer in men and the eighth most common one in women

  • We propose a system-level biochip for cell manipulations and impedance sensing in a 3 × 3 array by PC-based programming control and data acquisition

  • The cells moved to the middle electrode surface upon SU-8, the corresponding frequency was denoted as the upper bound of cross-over frequency

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Summary

Introduction

Bladder cancer is reported as the fourth most common type of cancer in men and the eighth most common one in women. During the diagnosis of bladder cancer, the identification of the grade needs to be taken into account when deciding the treatment. Cystoscopy is the surest way to examine the grade of bladder cancer from a biopsy of the lining of the bladder; the patient may need anesthesia for this procedure. A high accuracy, non-invasive and in vitro method for the determination of the stage of bladder cancer is necessary to help bladder cancer patients. There has been considerable and growing interest in an electrical detection method and dielectrophoretic (DEP) manipulations for cell-based biochips because both are intrinsically electrical and microfluidic compatible. In 1999, Milner et al [1] proposed an impedance technique for detecting a dielectrophoretic collection of microbiological particles by two coplanar microelectrodes

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