Portable devices with advantages of rapid,on-site,user-friendly and cost-effective assessment are highly demanded for applications in the field of first responders in disaster situations,healthcare protection at home,poorly equipped medical test in rural areas,as well as environmental monitoring in field.However,only a limited number of quantitative portable devices are commercially available,among which personal glucose meter (PGM) is the most successful example and has been the most widely used.But PGM can only detect blood glucose as the unique target.Herein,we described a novel design by combining glucoamylase-trapped DNA-crosslinked hydrogel with PGM to build a handheld "sweet" hydrogel-PGM sensor (SH-PGM) and achieved cheap,fast,portable,user-friendly,equipment-free and quantitative detection of various non-glucose targets.As illustrated in Fig.1,the hydrogel was crosslinked by aptamer and its partly complementary DNA (Strand-A and Strand-B).Upon targets introduction,the hydrogel collapses because of the formation of aptamer-target complex and glucoamylase is released,which,as an element of enzymatic signal amplification and signal transduction,can catalyze the hydrolysis of the outside amylose to produce D-glucose for PGM quantitative readout,as illustrated in Fig.1.By optimizing of enzyme,hydrogel and reaction factors,sensitive,selective and quantitative detection of cocaine was achieved with detection limit of 3.8 μM (1.2 μg/mL) and 0~500 μM linear detection range (Fig.2),as well as similar results in complex body fluids such as urine (Fig.3A) and plasma (Fig.3B),which had a good agreement with standard method such as LC/MS (Fig.4).By simply replacing the crosslinking cocaine aptamer to an ATP aptamer,selective and sensitive ATP quantitation was further demonstrated in Fig.5,suggesting the general applicability of the method.Therefore,the SH-PGM system reported here has the potential to be used by the public for portable and quantitative detection of a wide range of targets.