Miniature sensor systems for biomedical diagnostics

Diabetes mellitus is a worldwide public health problem. This metabolic disorder results from insulin deficiency and hyperglycemia and is reflected by blood glucose concentrations higher or lower than the normal range of 80-120 mg/dl (4.4-6.6 mM). The disease is one of the leading causes of death and disability in the world. The complications caused by diabetes are numerous, including higher risks of heart disease, kidney failure, or blindness. Such complications can be greatly reduced through stringent personal control of blood glucose. The diagnosis and management of diabetes mellitus thus requires a tight monitoring of blood glucose levels. Accordingly, millions of diabetics test their blood glucose levels daily, making glucose the most commonly tested analyte. Although self-testing is considered a major advance in glucose monitoring, it is limited by the number of tests per day it permits. The inconvenience associated with standard finger-stick sampling deters patients from frequent monitoring. Such testing neglects the monitoring of night time variations. This means that measurements do not reflect the overall trends and patterns of the blood glucose level. Hence, they may result in poor approximation of blood glucose variations. Tighter glycemic control through more frequent measurements or continuous monitoring by means of glucose biosensors is desired for detecting sharp changes in the glucose level and triggering proper alarm in cases of hypo- and hyperglycemia. A miniature, wireless implantable glucose sensor, when implanted in subcutaneous tissue, can continuously measure glucose level, which can be interrogated at will by the patient and also recorded automatically. Real-time glucose monitoring can provide maximal information about changing blood glucose levels throughout day and night, including the direction, magnitude, duration, and frequency of such fluctuations. The concept of a feedback loop (sensing-delivery) system goes beyond diabetes monitoring. Such ability to deliver an optimal therapeutic dose in response to distinct changes in the body chemistry of each person offers a unique opportunity to deliver personalized medical care and will dramatically change the treatment of other diseases through tailored administration of drugs. There are still major challenges in achieving clinically accurate glycemic monitoring in connection to closed-loop systems aimed at optimal insulin delivery.

The piezoresistive biochemical sensor containing a special biocompatible polymer (hydrogel) with a sharp volume phase transition in the neutral physiological pH range near 7.4 can detect a specific analyte, for example glucose. Thereby the hydrogel-based biochemical sensors are useful for the diagnosis and monitoring of diabetes. In order to extend the lifetime and efficiency of implanted biosensors, a number of in vitro testing procedures should be performed in physiological model solutions to evaluate the functionality and biocompatibility of glucose sensors.

Topic: Development, design and in vitro testing of a piezoresistive glucose sensor

The objective of this work is to develop and test a reliable and long-term-stable glucose sensor for physiological glucose range between 1 and 20 mM. Content description: Design of a dip glucose sensor combining a glucose-sensitive hydrogel and a micro fabricated pressure sensor chip. Investigation of the response of the glucose-sensitive hydrogel at different regimes of the glucose concentration change and of the solution supply. Estimation of accuracy with which a sensor can track gradual changes in glucose in the range between 1 and 20 mM. Evaluation of the sensitivity, signal reversibility, and response time of the sensor in complex physiological solutions. Long term in vitro testing of the sensor in a complex physiological solution. Contact: PD Dr.-Ing. habil. M. Günther, Room: GLB 7-E08, Phone:+49 351 46335378

Topic: Microsensor system based on metabolically sensitive hydrogels

The objective of this work is the elimination of cross-sensitivity of a glucose-sensitive hydrogel to pH value of solution and development of a corresponding algorithm for its compensation. Content description: Development and design of a set-up for simultaneous measurement of glucose concentration and pH-value of solution with the help of an additional piezoresistive pH sensor. Design of a pH sensor combining a pH-sensitive hydrogel and a micro fabricated pressure sensor chip. Implementation of testing and calibrating procedures for pH sensor in the pH range of 7 – 7.5. Study of the response of glucose and pH sensors in solutions with different glucose concentrations and pH values. Evaluation of the influence of solution pH change on the signal of glucose sensor. Derivation of calibration algorithms and algorithms for the compensation of the cross-sensitivities of a glucose-sensitive hydrogel to pH value and ionic strength of solution. Contact: PD Dr.-Ing. habil. M. Günther, Room: GLB 7-E08, Phone:+49 351 46335378

Topic: Development and implementation of calibrating procedure for glucose sensors

The objective of this work is to develop and evaluate calibration algorithms for glucose sensors according to the method of initial rate determination in order to achieve an optimum between the sensor signal amplitude and the sensor response time. Content description: Measurement of the sensor output voltage during the swelling/deswelling process of the glucose-sensitive hydrogel layer due to small gradual glucose concentration changes in solution. Determination of the initial slopes of the measuring kinetic curves. Calibration of glucose sensor according to the method of initial rate determination. Evaluation of the corresponding calibration and measurement procedures and deriving calibration algorithms. Contact: PD Dr.-Ing. habil. M. Günther, Room: GLB 7-E08, Phone:+49 351 46335378