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Rapid and Sensitive Detection of Cancer Cells Based on the Photothermal Effect of Graphene Functionalized Magnetic Microbeads Hongyan Zhang, Zhen Zhang, Yanhong Wang, Chuanchen Wu, Qingling Li, and Bo Tang ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.6b09490 • Publication Date (Web): 14 Oct 2016 Downloaded from http://pubs.acs.org on October 16, 2016
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ACS Applied Materials & Interfaces
Rapid and Sensitive Detection of Cancer Cells Based on the Photothermal Effect of Graphene Functionalized Magnetic Microbeads Hongyan Zhang,†,‡,§ Zhen Zhang,‡,§ Yanhong Wang,‡ Chuanchen Wu,‡ Qingling Li†, Bo Tang,*,† †
College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation
Center of Functionalized Probes for Chemical Imaging, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan, 250014, PR China. ‡
College of Life Science, Shandong Normal University, Jinan, 250014, PR China.
KEYWORDS: cancer cell, graphene oxide, photothermal effect, magnetic microbead, membrane
ABSTRACT: A strategy based on immune-graphene oxide (GO)-magnetic microbead complex for the sensitive, rapid, portable and low-cost detection of cancer cells was developed. The high efficiency cell capture and high sensitive thermal contrast detection could be simultaneously achieved using magnetic microbeads and the photothermal effect of GOs. The temperature variation caused by irradiating the GOs with a laser was used to establish the standard curve of temperature variation and cancer cell number. Under optimal conditions, the limit of detection
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could reach 100 cells. 4T1 cells spiked in human blood could be successfully detected in 1.5 hours, and the recovery was between 90.8% and 116.5%.
INTRODUCTION In the past decades, paper- (or membrane-) based methods for the rapid detection of cancer cells have been developed steadily1-7. These methods are known for the rapid, portable, sensitive, and low-cost detection of cancer cells. As we know, the limit of detection for cancer cells could achieve 4000 cells by naked eyes on a lateral flow device1 and 500 cells·mL-1 with instrumentation based on surface plasmon resonance spectroscopy8, which needs to be further improved. Dovichi and Harris 9, 10 first applied photothermal effect to detection methods, thermal lens effect induced by laser was used for calorimetric trace analysis. Qin et al 11 applied the photothermal effect of gold nanoparticles (GNPs) to lateral flow strip assays, and established a linear relationship between the analyte’s concentration and the temperature variation. The analytical sensitivity was extended by 32-fold. Recently, a photothermal paper sensor for the selective and sensitive detection of 2,4,6 trinitrotoluene (TNT) down to 14 ng/cm2 was reported.12 To date, we found only these four reports using the photothermal effect for detection from PubMed database. Application of a new material with better photothermal effect could improve the sensitivity of the detection method. Graphene oxides (GOs) also have commendable photothermal effect,13, 14 which have been utilized for the thermal therapy of malignant tumors.15-21 Our research team has reported a novel paper-based dot immune-graphene-gold filtration assay based on the photothermal effect of GO-Au nanocomposite for the detection of breast cancer cells as a short communication. 22 In this paper, the photothermal effects of GOs and GNPs were investigated
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detailedly, and the method of membrane filtration combined with magnetic separation established by our team23 was introduced to achieve higher sensitivity. The above-mentioned method of membrane filtration combined with magnetic separation was established using a size-amplified immune magnetic microbead strategy to realize the rapid detection of circulating tumor cells (CTCs) with a high capture efficiency and high purity.23 Direct microscopic counting was used to detect the CTCs after the incubation and capture procedure. This method was suitable for the detection of samples with a small number of cancer cells.23 However, the number of CTCs in some middle-advanced patients could reach several hundred and even thousands. 24 At this point, direct microscopic counting was sometimes timeconsuming, laborious and not easy to achieve. Thus, a strategy based on the photothermal effect of graphene functionalized on magnetic microbeads was presented. The cell capture and thermal contrast detection could be simultaneously achieved using magnetic microbeads and the photothermal effect of GOs. This strategy was suited to samples with a relatively large number of cancer cells and could be used as a supplement to the microscopic counting method. These two methods had the same incubation and capture procedures but different detection modes; thus, the samples, after incubation and capture, could firstly be observed under an optical microscope. If the number of cells was small (
