Rapid and Label-Free Separation of Burkitt's Lymphoma Cells from Red Blood Cells by Optically-Induced Electrokinetics

Abstract

Early stage detection of lymphoma cells is invaluable for providing reliable prognosis to patients. However, the purity of lymphoma cells in extracted samples from human patients' marrow is typically low. To address this issue, we report here our work on using optically-induced dielectrophoresis (ODEP) force to rapidly purify Raji cells' (a type of Burkitt's lymphoma cell) sample from red blood cells (RBCs) with a label-free process. This method utilizes dynamically moving virtual electrodes to induce negative ODEP force of varying magnitudes on the Raji cells and RBCs in an optically-induced electrokinetics (OEK) chip. Polarization models for the two types of cells that reflect their discriminate electrical properties were established. Then, the cells' differential velocities caused by a specific ODEP force field were obtained by a finite element simulation model, thereby established the theoretical basis that the two types of cells could be separated using an ODEP force field. To ensure that the ODEP force dominated the separation process, a comparison of the ODEP force with other significant electrokinetics forces was conducted using numerical results. Furthermore, the performance of the ODEP-based approach for separating Raji cells from RBCs was experimentally investigated. The results showed that these two types of cells, with different concentration ratios, could be separated rapidly using externally-applied electrical field at a driven frequency of 50 kHz at 20 Vpp. In addition, we have found that in order to facilitate ODEP-based cell separation, Raji cells' adhesion to the OEK chip's substrate should be minimized. This paper also presents our experimental results of finding the appropriate bovine serum albumin concentration in an isotonic solution to reduce cell adhesion, while maintaining suitable medium conductivity for electrokinetics-based cell separation. In short, we have demonstrated that OEK technology could be a promising tool for efficient and effective purification of Raji cells from RBCs.

Rapid Assembly of Carbon Nanoparticles Into Electrical Elements by Optically-Induced Electroosmotic Flow

“…The 50-nm-diameter CNPs (Sigma-Aldrich, U.S.A.) were suspended in deionized (DI) water and bovine serum albumin (BSA) with a conductivity of 1 × 10 −3 S/m (measured using the Cond 3110 conductivity meter). The purpose of adding BSA into the solution was described and discussed in our previous study [19]. Then, 18 μL of the CNP solution was injected into the OEK microfluidics chip by the micropump.…”

Dielectrophoretic behavior of a single cell when manipulated by optoelectronic tweezers: A study based on COMSOL ALE simulations

“…The sphere accelerated to the edge of the illuminated area as the electric field strength increases. To compare with them, sphere velocities about both of methods have the same order of magnitudes for the Raji and blood red cells referring to Liang's research [17,18]. Because the electrohydronamic flow is neglected, the velocity of sphere is less than Liang's simulation results.…”

Micro and Nano Manipulation and Assembly by Optically Induced Electrokinetics

“…Static light patterns used to trigger the ODEP force can be generated through a photomask [22], a diaphragm [31], or a single focused laser spot [25,32]. Dynamic or programmable manipulation can be achieved by a DMD [18,33,34], a projector [35,36], or a liquid-crystalbased spatial light modulator [37,38]. Additional optical components, including an objective lens, are usually needed to focus light patterns on to the photosensitive layer to obtain a resolution of 1-20 μm [19].…”

“…If the particles are nonhomogeneous, for example, biological cells, the CM factor requires a modification during manipulation [36,49,50].…”

“…Hwang et al [96] managed to differentiate normal oocytes from nutrient-starved abnormal oocytes on the basis of positive ODEP force and the reduction in friction force caused by the balance of gravity and the pulling-up component of the ODEP force (Figure 2.15b). Liang et al [36] reported a rapid negative ODEP force-based method for purifying Raji cell from red blood cells using a label-free process (Figure 2.15c).…”