Optoelectrochemical biorecognition by optically transparent highly conductive graphene-modified fluorine-doped tin oxide substrates.

Both optical and electrochemical graphene-based sensors have gone through rapid development, reaching high sensitivity at low cost and with fast response time. However, the complex validating biochemical operations, needed for their consistent use, currently limits their effective application. We propose an integration strategy for optoelectrochemical detection that overcomes previous limitations of these sensors used separately. We develop an optoelectrochemical sensor for aptamer-mediated protein detection based on few-layer graphene immobilization on selectively modified fluorine-doped tin oxide (FTO) substrates. Our results show that the electrochemical properties of graphene-modified FTO samples are suitable for complex biological detection due to the stability and inertness of the engineered electrodic interface. In addition, few-layer immobilization of graphene sheets through electrostatic linkage with an electrochemically grafted FTO surface allows obtaining an optically accessible and highly conductive platform. As a proof of concept, we used insulin as the target molecule to reveal in solution. Because of its transparency and low sampling volume (a few microliters), our sensing unit can be easily integrated in lab-on-a-chip cell culture systems for effectively monitoring subnanomolar concentrations of proteins relevant for biomedical applications.

In vivo induction of myeloid suppressor cells and CD4(+)Foxp3(+) T regulatory cells prolongs skin allograft survival in mice.

Natural CD4(+)Foxp3(+) T regulatory (Treg) cells can promote transplantation acceptance across major histocompatibility complex (MHC) barriers, while myeloid-derived suppressor cells (MDSCs) inhibit effector T-cell responses in tumor-bearing mice. One outstanding issue is whether combining the potent suppressive function of MDSCs with that of Treg cells might synergistically favor graft tolerance. In the present study, we evaluated the therapeutic potential of MDSCs and natural Treg cells in promoting allograft tolerance in mice by utilizing immunomodulatory agents to expand these cells in vivo. Upon administration of recombinant human granulocyte-colony stimulating factor (G-CSF; Neupogen), or interleukin-2 complex (IL-2C), Gr-1(+)CD11b(+) MDSCs or CD4(+)Foxp3(+) Treg cells were respectively induced at a high frequency in the peripheral lymphoid compartments of treated mice. Interestingly, induced MDSCs exhibited a more potent suppressive function in vitro when compared to MDSCs from naive mice. Furthermore, in vivo coadministration of Neupogen and IL-2C induced MDSCs at percentages that were higher than those seen when either agent was administered alone, suggesting an additive effect of the two drugs. Although treatment with either IL-2C or Neupogen led to a significant delay of MHC class II disparate allogeneic donor skin rejection, the combinatorial treatment was superior to either alone. Importantly, histological assessment of surviving grafts revealed intact morphology and minimal infiltrates at 60 days posttransplant. Collectively, our findings demonstrate that concurrent induction of MDSCs and Tregs is efficacious in downmodulating alloreactive T-cell responses in a synergistic manner and highlight the therapeutic potential of these naturally occurring suppressive leukocytes to promote transplantation tolerance.