The determination of glucose is important for the process control

Glucose Sensors

The determination of glucose is important for the process control. Assimilation of glucose by micro-organisms can be determined by an oxygen electrode because respiration activity increases after assimilation of organic compounds. Therefore, it is possible to construct a microbial electrode sensor for glucose using immobilized whole cells which utilize mainly glucose and an oxygen electrode.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Center for Research Resources (NCRR) invite investigator-initiated research grant applications to develop a glucose sensor or to create a closed-loop system for regulating blood glucose. Commercial development of needle-based sensors and minimally invasive sensors is underway. Several optical approachesare appealing and are worthy of further development but are unlikely to yield a functioning sensor in the near future. This Request for Applications (RFA) is intended to stimulate the application of advances in chemistry, engineering, cell biology, biochemistry and endocrinology to the development of novel technologies (which may include a combination of cellular and mechanical approaches) to reliably and accurately measure glucose levels as part of a system to maintain euglycemia.

A microbial electrode consisting of immobilized whole cells of Pseudomonas Fluorescens and a oxygen electrode was developed for the determination of glucose. The microbial sensor for glucose was applied to molasses. The concentration of glucose was determined both by the microbial sensor and by the enzymatic method. Satisfactory comparative results were obtained. Glucose in molasses was determined with an average relative error of % 10 by the microbial sensor.

Glucose sensors for the treatment of diabetes hold great promise for improving metabolic control and quality of life for persons with diabetes. The singlegreatest change in the management of both type 1 and type 2 diabetes in the past two decades has been the introduction and widespread implementation of reliable, accurate, and relatively "user-friendly" self-glucose monitoring devices. At present, state-of-the-art technology cleanly divides mechanical delivery devices and glucose sensing technology; however, the ultimate goal would be to develop a "closed-loop" delivery system by combining the two technologies.

Scope and Objectives:

Despite the enormous success of self-glucose monitoring, the technical challenges of developing methods for continuous monitoring of blood glucose and several highly publicized industry failures have overshadowed recent progress in the field of glucose sensing. Several approaches for continuous glucose measurement are close to clinical applicability.

Various glucose sensor designs are in development. Designs that utilize an enzyme electrode (such as glucose oxidase) and either a hydrogen peroxide or an oxygen detection system appear to be the most successful to date. These electrodes can be placed subcutaneously or intravenously. Other glucose sensor designs being examined include acute microdialysis systems, transdermal extraction of tissue fluids for glucose assay, and non- invasive technologies. Future designs may incorporate glucose sensing/alarm systems that are operational in vivo, such as isolated islet electrical activity as a sensor. These designs require more basic research before demonstration of feasibility and subsequent development.

This RFA invites applications to improve or test sensors currently under examination and to develop new approaches. In this regard, understanding the molecular mechanism by which ambient glucose concentrations elicit cellular responses may yield new approaches to measuring glucose with potential applications for glucose monitoring. These can include the molecular events leading to cellular recognition of hypo- or hyperglycemia.

The intended application of a specific sensor must be clearly defined, since it specifies the required technology. Also, the reproducibility of a sensor may be related to its fabrication method especially whether each sensor is individually made or mass-produced. In fact, mass production methods may need to be developed in hand with the clinical verification of a glucose sensor. Important functions to be included in the design and verification of a sensor are hypoglycemic alarm , continuous or frequent measurement of glucose levels, algorithms for converting glucose data to insulin dose requirements, and finally, linking glucose determinations to direct insulin delivery via a closed-loop system.The movement of glucose sensors into the clinical arena requires ascertainment of their longevity, the need for re-calibration, and the relationship between blood and subcutaneous glucose concentrations especially during exercise and hypoglycemia. The latter issue includes the evaluation of the lag-time from changes in blood glucose levels to changes in the subcutaneous tissue glucose levels, which may be affected by local physiologic factors, such as tissue architecture, microvascular perfusion, tissue oxygen distribution, movement,implant biocompatibility and wound healing. Assessment of this information requires further animal studies for certain devices, but other devices are ready to move into studies on normal volunteers and on volunteers with diabetes. The scope of the present solicitation includes the further development of glucose sensors to determine their clinical value and constraints; development and verification of fabrication methods; establishment of miniaturization procedures for the sensor and for control units; evaluation of the usefulness of the sensor in individuals with type 1 diabetes; and development of a closed-loop system with an accurate glucose sensing device, a controller, and an insulin delivery system. Relevant topics listed below are examples and should not be construed as required or limiting.

o Development of glucose sensors

o Investigation of relationship between blood glucose levels and dynamics in different tissues, including relative concentrations, characteristics of lag-times, determinants of partitioning

o Innovative, speculative approaches which incorporate cellular and mechanical technologies into the development of a glucose sensor

o Development of fabrication and/or miniaturization methods applicable to glucose sensors

o Examination of noninvasive or optical approaches to ascertain proof of concept and reliability especially related to variables affecting the path length and to inter-individual variability conferred by different skin types

o Independent assessment of clinical utility of a glucose sensor

o Integration of sensor, control and delivery systems and creation of a true artificial pancreas, which may include examination of appropriate parameters for control of glycemia with insulin, delivered peripherally or intraperitoneally

o Analysis of safety considerations of a closed-loop system with particular emphasis on the risk of over- or under-treatment

o Development of algorithms, telemetry, etc., to link the glucose sensor to the insulin delivery system

o Development of self-regulating implantable systems that are responsive to blood glucose levels