A biomimetic sensor surface to detect anti-β2-glycoprotein-I antibodies as a marker for antiphospholipid syndrome

Abstract

A biomimetic sensor has been developed, that allows for quantification of autoantibodies related to the antiphospholipid syndrome (APS). Autoantibodies directed against the β(2)-glycoprotein-I (β(2)GP-I) are known as the best markers for diagnosis of APS, however, detection of such antibodies is still a challenge. The epitopes of β(2)GP-I are exposed upon binding to negatively charged membranes. The surface of the sensor chips was therefore modified with such type of membranes, on which β(2)GP-I molecules were subsequently immobilized as recognition elements. Using the label-free method, reflectometric interference spectroscopy, it was possible to quantify anti-β(2)GP-I antibodies and to calibrate the sensor chip in buffer. A mild regeneration procedure allows for many consecutive measurements without stripping off the membrane in between.

Construction and Potential Applications of Biosensors for Proteins in Clinical Laboratory Diagnosis

“…Sensitive and accurate biosensing systems for these biomarkers can not only significantly aid in the early diagnosis and clinical management of AIDs but also help to establish therapeutic strategies [ 4 ]. Biosensors for the detection of autoantibodies specific to AIDs, including antiphospholipid syndrome (APS) [ 91 , 92 , 93 , 94 ], rheumatoid arthritis (RA) [ 95 , 96 , 97 , 98 , 99 ], systemic lupus erythematosus (SLE) [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ], multiple sclerosis (MS) [ 108 , 109 , 110 , 111 ], and celiac disease (CD) [ 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 ], are now constructed based on diverse techniques with many advantages, including high sensitivity and easy operation.…”

“…It worked in a serum matrix with a sample volume of 10 μL and was faster than the routinely performed ELISA [ 91 ]. A biomimetic optical sensor for APS-specific autoantibody β2-glycoprotein-I detection was constructed with an LOD of 5.62 mg L −1 [ 92 ]. A highly sensitive magnetic immunosensor was designed for anti-CCP autoantibodies based on SERS detection for the early diagnosis of RA [ 96 ], with an LOD as low as 13 pg mL −1 .…”

P1.01 - An optical sensor for studying hemocompatibility of biomaterials in a flow system

“…To form a phospholipid membrane the cleaned transducer was modified with dicarboxy-PEG (70 %) and phosphatidylcholine-PEG (30 %) analogous to the PEG surface modification. Phospholipid vesicles were prepared with phosphatidylcholine (70%) and cholesterol (30 %) using an already published method [5]. The phospholipid vesicles were formed in PBS and were pumped across the phosphatidylcholine-PEG surface on which the vesicles accumulated.…”

“…Using the association and dissociation curves recorded via RIfS, kinetical parameters of the interactions at the surface can be calculated [5]. This allows the assessment of the affinity of the investigated proteins to the respective surface.…”

Biomimetic Strategies for Sensing Biological Species

“…Generally speaking, this leads to very rapid sensor responses and comparably high sensitivities, because electroanalytical techniques that require direct contact between the analyte and the template become realistic. The group of Gauglitz [ 20 ] have developed a biomimetic sensor that allows quantification of autoantibodies related to the antiphospholipid syndrome (APS). The substantial challenge in this case is to overcome problems in establishing a reliable recognition element for assessing the target marker against β 2 -glycoprotein-I (β 2 GP-I): β 2 GP-I binds to negatively charged membranes and exposes the correct epitopes only in this bound state.…”