Michael J. Tierney

Clinical evaluation of the GlucoWatch® biographer: a continual, non-invasive glucose monitor for patients with diabetes ☆

A device providing frequent, automatic, and non-invasive glucose measurements for persons with diabetes has been developed: the GlucoWatch biographer. This device extracts glucose through intact skin via reverse iontophoresis where it is detected by an amperometric biosensor. The biographer can provide glucose readings every 20 min for 12 h. The performance of this device was evaluated in two large clinical studies in a controlled clinical environment (n=231), and the home environment (n=124). Accuracy of the biographer was evaluated by comparing the automatic biographer readings to serial finger-stick blood glucose (BG) measurements. Biographer performance was comparable in both environments. Mean difference between biographer and finger-stick measurements was -0.01 and 0.26 mmol l(-1) for the clinical and home environments, respectively. The mean absolute value of the relative difference was 1.06 and 1.18 mmol l(-1) for the same studies. Correlation coefficient (r) between biographer and finger-stick measurements was 0.85 and 0.80 for the two studies. In both studies, over 94% of the biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low BG levels. Biographer accuracy is relatively constant over all rates of BG changes, except when BG decreases more than 10 mmol l(-1) h(-1), which occurred for only 0.2% of points in the home environment study. Biographer precision, as measured by CV%, is approx. 10%. Skin irritation, characterized by erythema and edema, was either non-existent or mild in >90% of subjects and resolved in virtually all subjects without treatment in several days.

Glucose monitoring by reverse iontophoresis

Glucose can be extracted through intact skin by electro‐osmotic flow (a process called ‘reverse iontophoresis’) upon the application of a low‐level electrical current. Recently we have combined iontophoretic extraction with an in situ glucose sensor in a device called the GlucoWatch® biographer. Clinical results with this device show close tracking of blood glucose over a range of 2.2 to 22.2 mmol/l for up to 12 h using a single blood glucose value as calibration. The biographer readings lag behind blood glucose values by an average of 18 min. An analysis of data from 92 diabetic subjects in a controlled clinical setting shows a linear relationship (r=0.88) between GlucoWatch biographer readings and blood glucose. The mean absolute relative difference between the two measurements was 15.6% and more than 96% of the data fell in the (A+B) regions of the Clarke error grid. Similar results have been obtained from subjects using the GlucoWatch biographer in an uncontrolled home environment.

The GlucoWatch biographer: a frequent automatic and noninvasive glucose monitor.

The GlucoWatch® (Cygnus, Inc, Redwood City, CA, USA) biographer provides automatic, frequent and noninvasive blood glucose measurements for up to 12 h. The device extracts glucose through intact skin where it is measured by an amperometric biosensor. Clinical trials in a variety of environments have shown that the biographer provides accurate and precise glucose measurements when compared with serial fingerstick blood glucose measurements. Mean difference between these measurements was 0.26 mmol/L in the home environment (r = 0.80). Over 94% of biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low glucose levels. Biographer precision, as measured by coefficient of variation (CV)%, is approximately 10%. The low glucose alert function of the biographer was able to detect up to 75% of hypoglycaemic episodes with a low false alert level. Skin irritation, characterized by erythema and oedema was either nonexistent or mild in over 87% of subjects and resolved in virtually all subjects without treatment in several days. The GlucoWatch® biographer has been shown to be a safe and effective method to track glucose level trends and patterns, which should enable improved glycaemic control for many patients.

Effect of Acetaminophen on the Accuracy of Glucose Measurements Obtained with the GlucoWatch Biographer

BACKGROUND Improved glycemic control significantly reduces long-term microvascular complications of diabetes mellitus associated with chronic hyperglycemia. The GlucoWatch biographer is designed to facilitate intensive diabetes management by providing automatic, frequent, and noninvasive glucose readings up to three times per hour for as long as 12 hours. METHODS The device extracts glucose through intact skin using reverse iontophoresis and measures the extracted glucose with an electrochemical biosensor. A clinical trial was performed to assess the effect of acetaminophen, a potential interference for traditional blood glucose meters, on the accuracy of the GlucoWatch biographer in adult subjects with diabetes (n = 18). One thousand milligram doses of acetaminophen were administered to subjects in two groups: one to achieve Cmax (peak acetominophen concentration) at the time of biographer calibration and the other to achieve Cmax during the measurement period. The biographer readings were compared to serial fingerstick blood glucose measurements. RESULTS Time profiles over 9 hours show close tracking of the biographer glucose results with fingerstick blood glucose measurements for all groups. The mean difference between the two measurements is between 8 and 12 mg/dL for all groups. The mean absolute value of the relative difference is less than 20%, and more than 93% of the points were in the clinically acceptable (A+B) region of the Clarke Error Grid. No statistically significant differences were found for any accuracy measurement across all groups. CONCLUSIONS The GlucoWatch Biographer provides frequent measurements of glucose over a 12-hour period with high accuracy. No effect of therapeutic dosage of acetaminophen on the accuracy of the glucose readings was found.

Electroanalysis of Glucose in Transcutaneously Extracted Samples

Glucose can be extracted through intact skin by electroosmosis upon application of a low-level electrical current. The amount of glucose extracted has been shown previously to correlate with blood glucose level. An amperometric, GOx-based biosensor was used to measure the amount of glucose in samples extracted from a nondiabetic volunteer every twenty minutes for five hours. The blank-subtracted current output from this sensor accurately tracked blood glucose changes and correlated with the capillary blood glucose values (average r>0.93) and a time lag of twenty minutes. This proof-of-feasibility is a prerequisite to the development of an integrated, wearable glucose monitor for diabetics combining both biosensor and iontophoresis functions.

Keeping watch on glucose

New monitors help fight the long-term complications of diabetes. While a great many innovative technologies have been proposed, only a fraction are in advanced stages of development. They fall into three categories: implantable monitors, transdermal (through the skin) meters, and meters depending on spectroscopic methods. Each is a far cry from the painful methods used over the last several decades. By offering greater convenience and less pain, the devices encourage people to test more frequently, the extra testing providing previously unobtainable information on trends in glucose levels in response to insulin dosage and other treatments. Also, monitors that provide frequent, automatic readings can be equipped with preset alarms to warn the user of high or low glucose levels. Parents of children with diabetes, for example, can be warned of overnight low glucose, rather than having to wake up each night to check their childs blood sugar. These advances will lead to better decisions about treatment and ultimately reduce the long-term medical complications of diabetes.

Design, Development, and Evaluation of a Novel Microneedle Array-based Continuous Glucose Monitor:

Background: The development of accurate, minimally invasive continuous glucose monitoring (CGM) devices has been the subject of much work by several groups, as it is believed that a less invasive and more user-friendly device will result in greater adoption of CGM by persons with insulin-dependent diabetes. Methods: This article presents the results of preliminary clinical studies in subjects with diabetes of a novel prototype microneedle-based continuous glucose monitor. In this device, an array of tiny hollow microneedles is applied into the epidermis from where glucose in interstitial fluid (ISF) is transported via passive diffusion to an amperometric glucose sensor external to the body. Results: Comparison of 1396 paired device glucose measurements and fingerstick blood glucose readings for up to 72-hour wear in 10 diabetic subjects shows the device to be accurate and well tolerated by the subjects. Overall mean absolute relative difference (MARD) is 15% with 98.4% of paired points in the A+B region of the Clarke error grid. Conclusions: The prototype device has demonstrated clinically accurate glucose readings over 72 hours, the first time a microneedle-based device has achieved such performance.

Required technology breakthroughs to assume widely accepted biosensors

Silicon microsensors have been very successful over the last decade in a wide variety of applications. Although commercialization of silicon-based biosensors has been slow, careful applications of microfabrication technologies to the development of biosensors will drive the formation of many new markets. The most promising high-volume, emerging markets include clinical analysis, health care, and environmental. For example, the worldwide sales of clinical sensors are expected to reach several hundreds of millions by 2000, whereas the total worldwide market for biosensors is forecast to reach

Microelectrochemical sensor for nitrogen oxides

1 billion by the year 2000.In this article, an overview of current and potential markets is presented with an emphasis on technological barriers to overcome before biosensors will become more widely accepted. We start by explaining the relative success of physical sensors compared to biosensors. Subsequently, we review several biosensor approaches and techniques and their associated problems. Finally, the markets that these sensors are meant to serve are analyzed.

Multilayer ionic devices fabricated by thin- and thick-film technologies

Abstract A sensor for nitrogen oxides is presented based on the Back Cell™ sensor design. This unique sensor design allows response times many times faster than those of conventional amperometric gas sensors to be achieved. Conventional amperometric NO sensors operating at an NO oxidation potential suffer from interference caused by oxidation of NO2, which occurs in the same potential range. In the present sensing scheme, the sensor is operated at two different potentials. At the first potential, both NO and NO2 are oxidized; the second potential produces a reduction current proportional to NO2 concentration alone. This signal can be subtracted from the first signal to obtain an interference-free measurement of the NO concentration. In practice, the oxidation current when both NO and NO2 are present is higher than the sum of their individual currents, indicating a synergistic effect between the two gases. This type of NOx sensor may find application in environmental monitoring.