Efficient Simultaneous Detection of Metabolites Based on Electroenzymatic Assembly Strategy

Objective and Impact Statement:We describe an electroenzymatic mediator(EM)sensor based on an electroenzymatic assembly peak separation strategy,which can efficiently realize the simultaneous detection of 3 typical cardiovascular disease(CVD)metabolites in 5μl of plasma under one test.This work has substantial implications toward improving the efficiency of chronic CVD assessment.Introduction:Monitoring CVD of metabolites is strongly associated with disease risk.Independent and time-consuming detection in hospitals is unfavorable for chronic CVD management.Methods:The EM was flexibly designed by the cross-linking of electron mediators and enzymes,and 3 EM layers with different characteristics were assembled on one electrode.Electrons were transferred under tunable potential;3 metabolites were quantitatively detected by 3 peak currents that correlated with metabolite concentrations.Results:In this study,the EM sensor showed high sensitivity for the simultaneous detection of 3 metabolites with a lower limit of 0.01 mM.The linear correlation between the sensor and clinical was greater than 0.980 for 242 patients,and the consistency of risk assessment was 94.6%.Conclusion:Metabolites could be expanded by the EM,and the sensor could be a promising candidate as a home healthcare tool for CVD risk assessment.

Integrated microdevice with a windmill-like hole array for the clog-free,efficient,and self-mixing enrichment of circulating tumor cells

Circulating tumor cells(CTCs)have tremendous potential to indicate disease progression and monitor therapeutic response using minimally invasive approaches.Considering the limitations of affinity strategies based on their cost,effectiveness,and simplicity,size-based enrichment methods that involve low-cost,label-free,and relatively simple protocols have been further promoted.Nevertheless,the key challenges of these methods are clogging issues and cell aggregation,which reduce the recovery rates and purity.Inspired by the natural phenomenon that the airflow around a windmill is disturbed,in this study,a windmill-like hole array on the SU-8 membrane was designed to perturb the fluid such that cells in a fluid would be able to self-mix and that the pressure acting on cells or the membrane would be dispersed to allow a greater velocity.In addition,based on the advantages of fluid coatings,a lipid coating was used to modify the membrane surface to prevent cell aggregation and clogging of the holes.Under the optimal conditions,recovery rates of 93%and 90%were found for A549 and HeLa cells in a clinical simulation test of our platform with a CTC concentration of 20-100 cells per milliliter of blood.The white blood cell(WBC)depletion rate was 98.7%(n=15),and the CTC detection limit was less than 10 cells per milliliter of blood(n=6).Moreover,compared with conventional membrane filtration,the advantages of the proposed device for the rapid(2 mL/min)and efficient enrichment of CTCs without clogging were shown both experimentally and theoretically.Due to its advantages in the efficient,rapid,uniform,and clog-free enrichment of CTCs,our platform offers great potential for metastatic detection and therapy analyses.