Noninvasive ultrasonic glucose sensing with large pigs (approximately 200 pounds) using a lightweight cymbal transducer array and biosensors

Abstract

Background: To prevent complications in diabetes, the proper management of blood glucose levels is essential. Since conventional glucose meters require pricking fingers or other areas of the skin, a noninvasive method for monitoring blood glucose levels is desired. Using a lightweight cymbal transducer array, this study was conducted to noninvasively determine the glucose levels of pigs having a similar size to humans.

Method: In vivo experiments using eight pigs (approximately 200 pounds) were performed in five groups. A cymbal array with four biosensors was attached to the axillary area of the pig. The array was operated at 20 kHz at special peak-temporal peak intensity (I(sptp)) equal to 50 or 100 mW/cm(2) for 5, 10, or 20 minutes. After the ultrasound exposure, glucose concentrations of the interstitial fluid were determined using biosensors. For comparison, glucose levels of blood samples collected from the ear vein were measured by a commercial glucose meter.

Result: In comparison, glucose levels determined by a cymbal array and biosensor system were close to those measured by a glucose meter. After a 20-minute ultrasound exposure at I(sptp) = 100 mW/cm(2), the average glucose level determined by the ultrasound system was 175 +/- 7 mg/dl, which is close to 166 +/- 5 mg/dl measured by the glucose meter.

Conclusion: Results indicate the feasibility of using a cymbal array for noninvasive glucose sensing on pigs having a similar size to humans. Further studies on the ultrasound conditions, such as frequency, intensity, and exposure time, will be continued for effective glucose sensing.

Figure 1.

(A) A cymbal transducer consisting of a ceramic disk sandwiched between two brass end caps resonates at 20 kHz. Displacement of the ceramic disk is converted into the axial displacement of end caps. Dashed lines represent the flexing of end caps, and arrows indicate the motion. (B) A lightweight cymbal array was constructed using four cymbal transducers, which were connected in a 2 × 2 pattern and encased in a polymer.

Figure 2.

An enzyme-based electrochemical biosensor. The sensor consists of three electrodes: working/sensing, counter, and reference.

Figure 3.

(A) Layout of the glucose sensor incorporated with the cymbal array placed on the skin surface. After fixing the hydrogel of glucose oxidase on the biosensor, four biosensors were placed between the cymbal array and the standoff. (B) An ultrasonic glucose-sensing experiment with a pig placed in a lateral recumbent position. The reservoir within the standoff was filled with PBS through a small hole in the back of the array.

Figure 4.

Glucose concentrations of interstitial fluid were determined using an ultrasound system consisting of the cymbal array and enzyme-based biosensors. In comparison to the measurement by an Accu-Check glucose meter and an i-STAT analyzer, the result of ultrasonic measurement with I_sptp = 100 mW/cm² for 10 minutes has shown reliable accuracy.