In this study, the asymmetrically modified gold nanoparticles (AuNPs) with relatively large size are proposed for
highly sensitive detection of melamine in raw milk. At first, we found that the sensitivity of colorimetric detection
of melamine based on the conventional citrate-stabilized AuNPs could be significantly increased (limit of
detection by visual observation: from 1 μmol L−1 to 1 nmol L−1) via enlarging the size of AuNPs (from 13 to
42 nm). However, the large-sized AuNPs are unstable in the solution, and the accuracy of relevant aggregationbased
colorimetric detection method is dramatically decreased due to the rapid evanishment of the color of
solution caused by the precipitation of large-scaled AuNPs aggregates after introducing melamine. In view of this
limitation, the stabilizing agent polyethylene glycol (PEG) is introduced onto the selected area at the surface of
AuNPs to stabilize the large-sized AuNPs sensor and further adjust the aggregation behavior in an oriented and
controllable manner. As a result, the addition of melamine into asymmetrically PEGylated AuNPs with large size
could still induce a color change from purple to blue, but the color change could be maintained in aqueous
solution for a long time. This improvement is mainly caused by forming stable and oriented oligomers of AuNPs
taking advantage of the asymmetrical modification of AuNPs with PEG chain in this system. Such a way of
aggregation leads to remarkably enhanced long-term stability and an at least 2 orders of magnitude wider
dynamic detection range (1.05 nmol L−1 to 1 mmol L−1) compared with conventional AuNPs sensors. Finally,
such a novel asymmetrically modified AuNPs sensor is successfully applied to detect melamine in the raw milk
with the satisfactory spiked recovery from 99.6% to 103.7% and RSD of about 3.0%. This work provides a
sensitive and reliable method to detect melamine in pretreated milk, indicating a new avenue to make innovation
on colorimetric sensors for real sample detection.