Thermo-responsive imprinted hydrogel with switchable sialic acid recognition for selective cancer cell isolation from blood

In this work,a sialic acid(SA)-imprinted thermo-responsive hydrogel layer was prepared for selective capture and release of cancer cells.The SA-imprinting process was performed at 37℃ using thermo-responsive functional monomer,thus generating switchable SA-recognition sites with potent SA binding at 37℃and weak binding at a lower temperature(e.g.,25℃).Since SA is often overexpressed at the glycan terminals of cell membrane proteins or lipids,the SA-imprinted hydrogel layer could be used for selective cancer cell recognition.Our results confirmed that the hydrogel layer could efficiently capture cancer cells from not only the culture medium but also the real blood samples.In addition,the captured cells could be non-invasively released by lowing the temperature.Considering the non-invasive processing mode,considerable capture efficiency,good cell selectivity,as well as the more stable and durable SA-imprinted sites compared to natural antibodies or receptors,this thermo-responsive hydrogel layer could be used as a promising and general platform for cell-based cancer diagnosis.

Programmable Analytical Feature of Ratiometric Electrochemical Biosensor by Alternating the Binding Site of Ferrocene to DNA Duplex for the Detection of Aflatoxin B1

Ratiometric biosensor is among the promising strategies for the advanced analysis;its applicability in multiple scenarios,however,is seriously limited for the fixed analytical feature.Here,we reported ratiometric electrochemical biosensors with programmable analytical feature by alternating the binding site of ferrocene(Fc)to DNA duplex for the detection of aflatoxin B1(AFB1).DNA duplex was synthesized with AFB1 aptamer and its complementary DNA(cDNA)with Fc molecular tagged on aptamer or cDNA.For analysis,aptamer-AFB1 complex stripped from the electrode,and free cDNA triggered hybridization chain reaction to produce double-stranded DNA for methylene blue(MB)absorption.In this way,redox currents of Fc(I_(Fc))and absorbed MB(I_(MB))at the electrode were collected to produce the ratiometric signal of I_(MB)/I_(Fc)as a yardstick for AFB1.When Fc was tagged on aptamer,IFc decreased with higher concentration of AFB1(C_(AFB1)),the resultant biosensor allowed detection with an On/Off(I_(MB)/I_(Fc))mode;when Fc was tagged on cDNA,I_(Fc) kept constant as C_(AFB1)varying,offering an On/Constant(I_(MB)/I_(Fc))mode for the detection.Consequently,biosensor with On/Off mode showed a linear range of 0.1—100 pg/mL with a limit of detection(LOD)of 0.0650 pg/mL,while biosensor with On/Constant mode offered a wider linear rang of 1—10000 pg/mL but a relatively poor LOD of 0.330 pg/mL.Our work revealed the vital importance of binding site of probes to DNA,and this principle can endow ratiometric biosensor with programmable analytical feature(e.g.,linear range,LOD),allowing detections in various scenarios.