Detection of 1,5-Anhydroglucitol by Electrochemical Impedance Spectroscopy

Abstract

Background: Multiple markers are used to assess glycemic control in patients with diabetes mellitus (DM). New technology that permits simultaneous detection of multiple biomarkers combined with those used at the point of care indicative of glycemic control, including glycemic variability determined from 1,5-anhydroglucitol measurement, could provide better management and further insight into the disease. Methods:This platform was based on previous research involving glucose detection and uses electrochemical impedance spectroscopy to detect a range of 1,5-anhydroglucitol concentrations at an optimal binding frequency. The enzyme pyranose oxidase was fixed to gold electrodes while a sine wave of sweeping frequencies was induced in purified solutions and in variable presence of whole blood. Results:The optimal binding frequency for the detection of 1,5-anhydroglucitol was found to be 3.71 kHz. The impedance response compared to the concentration of target present was found to have a logarithmic slope of 7.04 with an R-squared value of 0.96. This response includes 2 experimental sets, a single test of a low concentration range and a high concentration range with 5 replicates. The relative standard deviation of the high range varied from 28% to 27% from lowest to highest concentrations. Best detection in complex solutions was found in lower blood concentrations of 0.5% and 1%, but maintained relatively high accuracy in concentrations 5% and 10%. Conclusions:The sensor platform was successfully evaluated at a high dynamic range of 1,5-AG in purified solutions. In the presence of whole blood, lowest percentages yielded the best results indicating that filtering interferents may be necessary in final device architecture.

Enhancing Glycemic Control via Detection of Insulin Using Electrochemical Impedance Spectroscopy

“…EIS on the other hand, is a label free technique, and the sensor prototype can be translated into screen printed sensors, allowing the possibility of POC with portable device and disposable test strips similar to the setup of self-monitoring of blood glucose. 14,26 The Food and Drug Administration requires all glucose meters to be within 20% variance from standards. 27 Currently, the replicated results show that across all sample concentrations the %RSDs ranges from 5% to 26%, suggesting there are still room for improvements.…”

“…EIS on the other hand, is a label free technique, and the sensor prototype can be translated into screen printed sensors, allowing the possibility of POC with portable device and disposable test strips similar to the setup of self-monitoring of blood glucose. 14,26…”

“…While these techniques are specific and sensitive, they require specialized laboratory technicians and time consuming procedures. 14,15 There is a need for a simple, label free, and rapid insulin sensor suitable for a POC setting in addition to a glucose sensor. In this paper we report the groundwork of a rapid and label-free insulin sensor using EIS.…”

Towards the Future Development of an Electrochemical Continuous Multimarker Biosensor for Enhanced Glycemic Management

“…Verification and determination of OBFs specific to glycemic management has determined different OBF values for individual biomarkers. Shown in Figure 1A is the OBF for markers such as insulin at 810.5 Hz, 2 glucose at 1170 Hz, 1,5-anhydroglucitol 3,710 Hz, 6 glycated albumin at 1.18 Hz, and glycated hemoglobin of 547 Hz. Knowing the OBF allows for the use of a single electrode with multiple markers as shown in Figure 1B.…”

Direct Measurement of a Biomarker’s Native Optimal Frequency with Physical Adsorption Based Immobilization

“…A biomarker’s optimal frequency (OF) is generally accepted as the label-free electrochemical impedance spectroscopy (EIS) response that best reflects the binding of the biomarker to its molecular recognition element (MRE). − While the criteria of calculating the OF have not been universally defined, the OF has been advocated as an additional means of specificity to supplement the antibody–antigen reaction, while also reducing the assay time and hardware requirements for the measuring system. Many studies have identified the OFs of various biomolecules using either self-assembled monolayers (SAMs) or various surface coatings to supply the needed functional groups for immobilization. − However, whether each biomarker still possesses its native OF without the use of a long, electrically insulted spacer (i.e., SAM) or other surface coating remains to be investigated. To study a biomarker’s native OF, it is necessary to construct an experimental platform without potential interference from complex immobilization reactions.…”