Multivalent interaction-based carbohydrate biosensors for signal amplification

Abstract

Multivalent interaction between boronic acids immobilized on Quartz Crystal Microbalance (QCM) sensor surface and the carbohydrates modified Au -nanoparticle (AuNP) has been demonstrated for the development of a sensitive carbohydrate biosensor. Briefly, a boronic acidcontaining polymer (boropolymer) as multivalent carbohydrate receptor was oriented immobilized on the cysteamine coated electrode through isourea bond formation. Carbohydrates were conjugated to AuNPs to generate a multivalent carbohydrates moiety to amplify the response signal. Thus, the binding of the carbohydrate conjugated AuNPs to the boropolymer surface are multivalent which could simultaneously increase the binding affinity and specificity. We systematically studied the binding between five carbohydrate conjugated AuNPs and the boropolymer. Our studies show that the associate constant (K a ) was in the order of fucose < glucose < mannose < galactose < maltose. A linear response in the range from 23 µM to 3.83 mM was observed for mannose conjugated AuNPs and the boropolymer recognition elements, with the lower detection limit of 1.5 µM for the carbohydrate analytes. Furthermore, the multivalent binding between carbohydrates and boronic acids are reversible and allow the regeneration of boropolymer surface by using 1M acetic acid so as to sequentially capture and release the carbohydrate analytes.

Electrochemical biosensor for detection of DNA hydroxymethylation based on glycosylation and alkaline phosphatase catalytic signal amplification

“…As a result, the glucosyl group was covalently modified on the hydroxymethyl of target DNA. It is well known that boronic acid can covalently bind with 1,2-or 1,3-diol group of the carbohydrates (such as glucose) to form esters in alkaline solution, thus boronic acid and its derivatives (such as 3-aminophenylboronic acid, 4-aminophenylboronic acid, 4-mercaptophenylboronic acid) have been widely applied in electrochemical sensor for immobilizing glycoprotein, antibody and enzymes [27][28][29][30][31][32]. In this work, we selected PDBA as bridging agent and ALP capturing reagent.…”

Applying Multivalent Biomolecular Interactions for Biosensors

“…For many targets and receptors, therefore, enhanced binding affinities by multivalency have been used to improve the detection limits of diverse biosensors. For example, multivalent sialic acids with strong lectin binding affinities provided an improved limit‐of‐detection (i.e., sensitivity) . Multivalent binding between complementary DNAs also offers superior DNA hybridization.…”

“…For example, multivalent sialic acids with strongl ectin binding affinities provided an improved limit-of-detection( i.e.,s ensitivity). [31] Multivalent binding betweenc omplementary DNAs also offers superior DNA hybridization. Intact microRNAsw ere measured down to attomolar concentrations by multivalent hybridization between three pieces of DNA/RNA fragments.…”

A Survey of the 2010 Quartz Crystal Microbalance Literature

“…The ability of surfaces comprised of boropolymers with O‐cyanate modified ends to bind carbohydrates was determined and the surface construction was confirmed by QCM and AFM (Chalagalla et al ., ). Boronic acid surfaces on a QCM sensor were used to detect sugars attached to gold nanoparticles (fucose, glucose, mannose, galactose and maltose) (Wang et al ., ) with the nanoparticles used to amplify the sensor response.…”