An On-Chip Disposable Salivary Glucose Sensor for Diabetes Control

Abstract

Background: Self-management of blood glucose (BG) is considered a norm for diabetes control. However, this invasive process is uncomfortable for patients, especially when intensive measurements with frequent finger pricks are required. Saliva, an alternative body fluid that is easily accessible and contains trace amount of glucose can be potentially used for the noninvasive monitoring of diabetes.

Methods: As a solution for real-time glucose measurements using saliva for diabetic care, we have developed an on-chip disposable glucose nano-biosensor through a layer-by-layer assembly process. In this work, a clinical study of 10 healthy subjects was conducted to determine the potential usefulness of salivary glucose (SG) sensors for glycemic control.

Results: Findings revealed (1) the individual BG/SG ratio at fasting was consistent over an entire year when there was no significant change of personal health; (2) the individual SG levels tracked closely with BG levels after meals; (3) a time difference of 15-30 minutes exists between peak levels of BG and SG; (4) 2 hours after a meal, the BG/SG ratio returned to a similar value at fasting.

Conclusions: We propose to measure fasting and pre- and 2-hour postprandial SG levels for self-management of glycemic levels. As a result, this article is not intended to replace the common BG tests. With preliminary results, we believe SG itself could be used as means for reliable diabetes monitoring and a potential fluid for prognosis of future disease.

Keywords: biochemistry; diabetes; enzymology; oral diagnosis; saliva; salivary diagnostics.

Figure 1.

Laboratory setup of saliva sensing system. PVDF: polyvinylidene fluoride.

Figure 2.

Cyclic voltammetry tests determined steady-state calibration curve of SWNT/(CS/GNp/GOx)₃ functionalized Pt electrode at an applied potential by testing (A) glucose in PBS; (B) spiked salivary glucose. Error bars, ± standard deviation and n = 3.

Figure 3.

Amperometric tests of spiked salivary glucose with (A) current signal recorded at 30s, (B) integrated current signal of 27~30s with post data processing. Error bars, ± standard deviation and n = 3.

Figure 4.

(A) Saliva’s composition and size distribution. (B) Viscosity change of 4 individual saliva samples: unfiltered saliva (triangle); PVDF-filtered saliva (square). Error bars, ± standard deviation and n = 3.

Figure 5.

(A) Linear correlation between sensor and UV measured SG with obtained conversion formula. (B) Clark error grid analysis of SG sensors. Region A are those values within 20% of the reference values; region B contains points that are outside of 20% region but would not lead to inappropriate treatment so still are acceptable; region C contains points leading to unnecessary treatment; region D represents points indicating a potentially dangerous failure to detect hypoglycemia or hyperglycemia; region E includes points that would confuse treatment of hypoglycemia for hyperglycemia and vice versa.

Figure 6.

Glucose monitoring test of subject B before and after (A) OGTT, (B) regular meal, (C) standardized meal. The primary vertical axis on the left is used for BG values (rhombus), the secondary vertical axis on the right is used for SG values (triangle).