In Vitro Diagnostics in Diabetes: Meeting the Challenge Anthony P.F. Turner, Beining Chen, * and Sergey A. Piletsky Diabetes is one of the leading causes of death and disability in the world. There is a large population in the world suffering from this disease, and the healthcare costs increase every year. It is a chronic disorder result- ing from insulin deficiency and hyperglycemia and has a high risk of development of complications for the eyes, kidneys, peripheral nerves, heart, and blood ves- sels. Quick diagnosis and early prevention are critical for the control of the disease status. Traditional biosen- sors such as glucose meters and glycohemoglobin test kits are widely used in vitro for this purpose because they are the two major indicators directly involved in diabetes diagnosis and long-term management. The market size and huge demand for these tests make it a model disease to develop new approaches to biosensors. In this review, we briefly summarize the principles of biosensors, the current commercial devices available for glucose and glycohemoglobin measurements, and the recent work in the area of artificial receptors and the potential for the development of new devices for diabe- tes specifically connected with in vitro monitoring of glucose and glycohemoglobin HbA 1c . © 1999 American Association for Clinical Chemistry Diabetes mellitus is a chronic disorder characterized by insulin deficiency, hyperglycemia, and a high risk of development of complications for eyes, kidneys, periph- eral nerves, heart, and blood vessels (1, 2). Diabetes is widely recognized as one of the leading causes of death and disability in the world. About 7% of the world’s population suffer from this disease, and the healthcare costs increase every year. An enormous amount of re- search has been devoted to this area to develop new diagnostic tools for the benefit of diabetic patients. Bio- sensors and bioassays have been intensively used for the in vitro diagnosis of diabetes. Most of them are based on the measurement of two important analytes, glucose and glycohemoglobin HbA 1c , because they are the two major indicators directly involved in diabetes diagnosis and long-term management. This review will focus on recent advances in the diagnosis or monitoring of these two analytes, present a summary of the current commercial techniques used, and consider the challenges for research intending to underpin the development of new devices for diabetes specifically connected with in vitro monitor- ing of glucose and glycohemoglobin HbA 1c . Biosensors “Biosensors are defined as analytical devices incorporat- ing a biological material (e.g., tissue, microorganisms, organelles, cell receptors, enzymes, antibodies, nucleic acids, and others), a biologically derived material, or biomimic intimately associated with or integrated within a physicochemical transducer or transducing microsys- tem, which may be optical, electrochemical, thermomet- ric, piezoelectric or magnetic” (3) (Fig. 1). Enzymes, nucleic acids, antibodies, receptors, mem- branes, intact cells, and tissue pieces have all been used for fabrication of biosensors (4). They can be used to make either catalytic or affinity sensors; in both cases, it is the binding reactions that provide the specificity. With cata- lytic sensors, there is a change in concentration of a component that can subsequently be detected, whereas with an affinity sensor the binding event itself is moni- tored. Enzymes are by far the most commonly used components in catalytic biosensors, whereas most affinity sensors are based on antibodies. Recently, artificial recep- tors have emerged that may offer viable alternative rec- ognition elements for biosensors, and this has become a fast-growing area for research (5). The five principal transducer classes are electro- chemical, optical, thermometric, piazoelectric, and magnetic (6). Electochemical sensors may be subdi- vided into potentiometric, amperometric, or conductio- metric. Potentiometric devices measure the change in charge density at the surface of an electrode, an example of which is an ion-selective, field-effect transistor for an Institute of BioScience and Technology, Cranfield University, Bedfordshire MK43 0AL, United Kingdom. *Author for correspondence. Fax 44-1234-750907; e-mail b.chen@ cranfield.ac.uk. Received May 14, 1999; accepted June 28, 1999. Clinical Chemistry 45:9 1596 –1601 (1999) Oak Ridge Conference 1596 Downloaded from https://academic.oup.com/clinchem/article/45/9/1596/5643479 by guest on 16 September 2020