Biosensor technology: Technology push versus market pull

Abstract

Biosensor technology is based on a specific biological recognition element in combination with a transducer for signal processing. Since its inception, biosensors have been expected to play a significant analytical role in medicine, agriculture, food safety, homeland security, environmental and industrial monitoring. However, the commercialization of biosensor technology has significantly lagged behind the research output as reflected by a plethora of publications and patenting activities. The rationale behind the slow and limited technology transfer could be attributed to cost considerations and some key technical barriers. Analytical chemistry has changed considerably, driven by automation, miniaturization, and system integration with high throughput for multiple tasks. Such requirements pose a great challenge in biosensor technology which is often designed to detect one single or a few target analytes. Successful biosensors must be versatile to support interchangeable biorecognition elements, and in addition miniaturization must be feasible to allow automation for parallel sensing with ease of operation at a competitive cost. A significant upfront investment in research and development is a prerequisite in the commercialization of biosensors. The progress in such endeavors is incremental with limited success, thus, the market entry for a new venture is very difficult unless a niche product can be developed with a considerable market volume.

Introduction

The field of biosensor technology was originated from the papers by Clark and Lyons (1962), Guilbault et al. (1962), Updike and Hicks (1967) and Guilbault and Montalvo (1969). Di Gleria et al. (1986) described a mediated electrochemical biosensor using ferrocene instead of dioxygen to alleviate electroactive interfering species such as uric and ascorbic acids. This elegant procedure formed the basis for successful commercialization of a glucose pen by Medisense. A biosensor is defined by The National Research Council (part of the U.S. National Academy of Sciences) as a detection device that incorporates a) a living organism or product derived from living systems (e.g., an enzyme or an antibody) and b) a transducer to provide an indication, signal, or other form of recognition of the presence of a specific substance in the environment. As a self-contained integrated receptor-transducer device, a biosensor consists of a biological recognition element in intimate contact or integrated with a transducer. Ideally, biosensors must be designed to detect molecules of analytical significance, pathogens, and toxic compounds to provide rapid, accurate, and reliable information about the analyte of interrogation. Biosensors have been envisioned to play a significant analytical role in medicine, agriculture, food safety, homeland security, bioprocessing, environmental and industrial monitoring. After the September 11, 2001 event, the detection of biohazards in the environment has become an important issue (Fuji-Keizai USA Inc., 2004, Rodriguez-Mozaz et al., 2005) as reflected by a significant increase in funding for biosensor research in relation to homeland security in the USA and some other countries (Fuji-Keizai USA, Inc., 2004) towards the development of hand-held biosensor technology. Recent incidences of contaminated foodstuffs have also heightened consumer concern. Lab tests for bacterial contamination in meat are required by regulators, but they are costly and slow; only yielding results after 2 to 3 days. Hence, food products remain stored in warehouses for longer periods. Albeit a plethora of workable biosensors for a variety of applications has been developed, besides the blood glucose and lactate biosensors and a few other commercial hand-held immunosensors in clinical diagnostics, only a minimal number of biosensors appear to be commercially feasible in the near future.

Annual worldwide investment in biosensor R&D is estimated to be $300 US million (Weetall, 1999, Alocilja and Radke, 2003, Spichiger-Keller, 1998). Both publications and patents issued are phenomenal in biosensor research. From 1984 to1990, there were about 3000 scientific publications and 200 patents on biosensors (Collings and Caruso, 1997, Fuji-Keizai USA Inc., 2004). The same number of publications (~ 3300 articles) but almost double the patent activity (400 patents) was noticed from 1991 to 1997. The explosion of nanobiotechnology from 1998 to 2004 had generated over 6000 articles and 1100 patents issued/pending (Fuji-Keizai USA, Inc., 2004). Thus, significant improvements in the biosensor performance in terms of selectivity and detection sensitivity, at least under well-controlled environments, have been realized to facilitate the applications of various biosensors. Such impressive publications and patents, doubtlessly, suggest a continuing bright future for R&D activities in biosensor technology with the health, drug discovery, food, homeland security, pharmaceutical and environmental sectors as the major beneficiaries (Hall, 1990, Andreescu and Sadik, 2004, Turner, 1996). However, the commercialization of biosensor technology has significantly lagged behind the research output. The rationale behind the slow technology transfer could be attributed to cost considerations and some key technical barriers such as stability, detection sensitivity, and reliability. The laboratory diagnostics market has changed considerably in the last decade and innovation in this segment will be increasingly driven by automation and system integration with high throughput for multiple tasks. Such requirements pose a great challenge in biosensor technology which is often designed to detect one single or a few target analytes. In addition, before the biosensor gains market acceptance, it must prove its effectiveness in the field test followed by its validation by well-established procedures. Lab studies with “fairly clean” samples often fail to provide an adequate measure of capability for “real-world” samples, leading to failed technology transfer and further investment. Such activities require appropriate sources of finance for technology development and demonstration. Ultimately, the success of biosensors must prove that it is the inevitable choice as a cost-effective analytical tool.

This report aims to provide an overview of biosensor technology with some highlighted advances in both the transducer element and the biorecognition molecule. Technical hurdles associated with the biosensor development/application in clinical chemistry, food safety, environment, and homeland security are addressed together with the identification of market opportunities and commercialization activities. These hurdles include relatively high development costs for single analyte systems and limited shelf and operational lifetimes of biorecognition components.