Enhanced Cell Capture on Functionalized Graphene Oxide Nanosheets through Oxygen Clustering

Abstract

With the global rise in incidence of cancer and infectious diseases, there is a need for the development of techniques to diagnose, treat, and monitor these conditions. The ability to efficiently capture and isolate cells and other biomolecules from peripheral whole blood for downstream analyses is a necessary requirement. Graphene oxide (GO) is an attractive template nanomaterial for such biosensing applications. Favorable properties include its two-dimensional architecture and wide range of functionalization chemistries, offering significant potential to tailor affinity toward aromatic functional groups expressed in biomolecules of interest. However, a limitation of current techniques is that as-synthesized GO nanosheets are used directly in sensing applications, and the benefits of their structural modification on the device performance have remained unexplored. Here, we report a microfluidic-free, sensitive, planar device on treated GO substrates to enable quick and efficient capture of Class-II MHC-positive cells from murine whole blood. We achieve this by using a mild thermal annealing treatment on the GO substrates, which drives a phase transformation through oxygen clustering. Using a combination of experimental observations and MD simulations, we demonstrate that this process leads to improved reactivity and density of functionalization of cell capture agents, resulting in an enhanced cell capture efficiency of 92 ± 7% at room temperature, almost double the efficiency afforded by devices made using as-synthesized GO (54 ± 3%). Our work highlights a scalable, cost-effective, general approach to improve the functionalization of GO, which creates diverse opportunities for various next-generation device applications.

Oxygen Clusters Distributed in Graphene with “Paddy Land” Structure: Ultrahigh Capacitance and Rate Performance for Supercapacitors

“…Graphene oxide (GO), an atom‐thick sheet of carbon functionalized with rich and interactive oxygen‐containing groups, is unsuitable for application in supercapacitors due to its poor conductivity . The theoretical calculations demonstrate that oxygen functional groups in GO can distribute on the carbon network in the form of clustered structure under certain conditions, indicating the existence of sp 3 carbon with oxygen groups distributed in graphitic domains (sp 2 carbon). It is worth mentioning that the as‐synthesized RGO with different oxygen concentrations of 5–30 at% depends on the reduction of GO under mild or harsh conditions, but the increased electrical conductivity of RGO comes at the expense of the decreased oxygen content .…”

Microfluidics and Nanomaterial-based Technologies for Circulating Tumor Cell Isolation and Detection

“…This linkage was found to have a high degree of mechanical stability and also demonstrates that click reactions can occur without interfering with natural biochemical processes that occur in organisms in vivo, which is tremendously beneficial for future diagnostic applications. Previously, a research group had used GO as a substrate in combination with single-domain antibody, protein modification, and click chemistry technologies so that the antibody can be immobilized unidirectional on the GO substrate, thereby establishing a functional device that can rapidly capture a small number of specific cells from the blood [100]. Other related studies have demonstrated that when antibodies are immobilized to a substrate by click chemistry, target specificity and sensitivity are greatly enhanced in addition to effectively maintaining the activity of the biological probe [101,102] (Figure 7A-D).…”

Optimizing Circulating Tumor Cells’ Capture Efficiency of Magnetic Nanogels by Transferrin Decoration

“…In addition, several nanomaterials such as carbon nanotubes [15], graphene-oxide nanosheets [16], nanowires and magnetic nanoparticles [17][18][19][20][21] have been investigated for the capture of CTCs.…”