4

5

6

7

8

9

S

B

A

B

TrembfioaapmTea

gthTcoinaionfrMsosuMOsuwCtr

5sethsea

L

Laane, C. et al. (1985) On optimizing organic solvents in multi-liquid-phase biocatalysis. Trends Biotechnol. 3, 251–252

Mattiasson, B. and Adlercreutz, P. (1991) Tailoring the microenvironmentof enzymes in water-poor systems. Trend Biotechnol. 9, 394–398

Blanc, P. and Goma, G. (1987) Propionic acid fermentation: improvementof performances by coupling continuous fermentation and ultrafiltration.Bioprocess Eng. 2, 137–139

Lohrasbi, M. et al. (2010) Process design and economic analysis of acitrus waste biorefinery with biofuels and limonene as products.Bioresour. Technol. 101, 7382–7388

Dua, M. et al. (2002) Biotechnology and bioremediation: successes andlimitations. Appl. Microbiol. Biotechnol. 59, 143–152

Nygren, P.A. et al. (1994) Engineering proteins to facilitatebioprocessing. Trends Biotechnol. 12, 184–188

10 Arvidsson, P. et al. (2003) Direct chromatographic capture ofenzyme from crude homogenate using immobilized metal affinitychromatography on a continuous supermacroporous adsorbent.J. Chromatogr. A 986, 275–290

11 North, J.R. (1985) Immunosensors: antibody-based biosensors. TrendsBiotechnol. 3, 180–186

12 Mattiasson, B. et al. (2009) Immunochemical binding assays fordetection and quantification of trace impurities in biotechnologicalproduction. Trends Biotechnol. 28, 20–27

0167-7799/$ – see front matter � 2012 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.tibtech.2012.11.003 Trends in Biotechnology, March 2013,

Vol. 31, No. 3

etters Trends in Biotechnology March 2013, Vol. 31, No. 3

no

S-5

Tmgpn[4lambamfiotiinuspte

pecial Issue: Celebrating 30 years of biotech

iosensors: then and now

nthony Turner

iosensors and Bioelectronics Centre, IFM, Linkoping University,

his 30th Anniversary issue is a perfect opportunity toflect on biosensors, then and now, because this time spanatches the exponential growth phase of this subject. Theirth of TIBTECH marked the emergence of this fledglingeld from a niche academic area, with one product of noten the market, to a multibillion dollar industry thatttracts the attention of commerce, governments, andcademe alike. Thirty years ago, you might have read aaper on biosensors once every 2 years and the total Worldarket was worth less than US$ 5 million per year.oday, around 4500 papers are published on biosensorsach year and worldwide sales of biosensors are worthbout US$ 13 billion (Figure 1).Before highlighting the landmark advances that trig-

ered this phenomenal growth, it is fitting to acknowledgee true pioneers of this discipline from earlier decades.he late Leyland C. Clark was the first to publish thencept of the modern-day biosensor, in his seminal paper

1962 [1]. Contemporaries in the USA, Gerry Guilbaultnd Garry Rechnitz, extended and expanded the concept ton-selective electrodes and the use of tissues as biorecog-ition elements. By the 1970s, new themes were emergingom Professor Suichi Suzuki’s protegees Isao Karube andasuo Aizawa, and whole-cell biosensors and immunosen-rs emerged. In both Eastern and Western Europe thebject took route with Klaus Mosbach (Sweden), Marcoascini (Italy), and Frieder Scheller (then East Germany).n the commercial scene, after a faltering start, the highlyccessful enzyme-electrode-based analyser for glucoseas launched by the Yellow Springs Instrument (YSI)ompany and became the instrument of choice for decen-alised analysis in diabetes clinics.So what was special about the 1980s? Looking back on the

-year period from the birth of TIBTECH, we can see thatveral paradigm-changing papers were published. By fare two most cited publications were on mediated glucose

nsors for home blood glucose monitoring [2] and biointer-ction analysis using surface plasmon resonance (SPR) [3].

Fi

ob

logy

8183, Sweden

hese two seminal publications laid the foundations for theost significant commercial biosensor products: disposablelucose sensors and SPR analysers. The third most citedaper from this era was the first detailed description of aeedle-type glucose sensor for subcutaneous implantation], which finally reached commercial fruition over 20 yearster, in the form of self-administered continuous glucoseonitoring devices for people with diabetes. Less recognisedy the academic community in terms of citations, but argu-bly equally important for the realisation of today’s com-ercial tests, is the capillary-fill device and evanescenteld-based fluorescence immunoassay [5]. The simple ideaf capillary fill is now ubiquitous in home diabetes diagnos-cs. Papers that might be considered ahead of their timeclude a vision of DNA biosensors [6] and descriptions of these of localised SPR [7]. The DNA chip was later to beectacularly realised by Stephen Fodor and the Affymetrixam and localised SPR has become a mainstay of current

World market for biosensors (US$m)

0

2000

4000

6000

8000

10 000

12 000

14 000

16 000

18 000

1985 1988 1995 1996 2000 2002 2004 2006 2009 2010 2018

TRENDS in Biotechnology

gure 1. Estimated past, present, and future world market for biosensors. Data

tained from a variety of primary and secondary commercial sources.

119

tfr

f

l

-

t

l

s,

r

n

hneedle-type glucose sensor. Lancet 2, 1129–1131

e

Letters Trends in Biotechnology March 2013, Vol. 31, No. 3

nanomaterial-based biosensors. Stimulated by the recenfabrication of the nanowire, there has been a revival ointerest in the concept of the immuno field-effect transisto(immunoFET), which was extensively explored in the early1980s [8]. Many of the fundamental hurdles to progress othis particular technology remain, but the hope is that thelocalisation of the signal enabled by nanofabrication wilavoid the troublesome interference effects from the bulksolution that dogged earlier microfabricated devices. Myfinal reference to early 1980s biosensor research is a personal favourite when describing the field to my students, the‘Bananatrode’ [9]. Although not the most intellectuallystimulating paper of the period, it certainly illustrates wha

sl,

ch

o

R,

f

ct

,

-s

crs

c

120

and security continue to attract major national andinternational funding initiatives. Thirty years and stilgoing strong!

References1 Clark, L.C. and Lyons, C. (1962) Electrode systems for continuou

monitoring in cardiovascular surgery. Ann. N. Y. Acad. Sci. 10229–45

2 Cass, A.E.G. et al. (1984) Ferrocene-mediated enzyme electrode foamperometric determination of glucose. Anal. Chem. 56, 667–671

3 Liedberg, B. et al. (1983) Surface-plasmon resonance for gas-detectioand biosensing. Sens. Actuators 4, 299–304

4 Shichiri, M. et al. (1982) Wearable artificial endocrine pancreas wit

l.

-a

c

n

a biosensor is with striking clarity to the dozing pupil.So what is there left to do? Although much has been

achieved, some goals remain as distant as they were 30 yearsago. Non-invasive monitoring of key metabolites such asglucose remains a pipe dream. Fully-wearable, implantable,or generally personalised biosensing devices are materialis-ing and we see real hope for the artificial pancreas, wearablesensors for elderly care, and distributed sensors for man-agement of acute trauma or post-operative care. Inexpen-sive consumer devices for disease diagnostics based on

5 Badley, R.A. et al. (1987) Optical biosensors for immunoassays – thfluorescence capillary-fill device. Philos. Trans. R. Soc. Lond. B: BioSci. 316, 143–160

6 Downs, M.E.A. et al. (1987) New DNA technology and the DNAbiosensor. Anal. Lett. 20, 1897–1927

7 Holland, W.R. and Hall, D.G. (1983) Surface-plasmon dispersionrelation – shifts induced by the interaction with localized plasmresonances. Phys. Rev. B 27, 7765–7768

8 Janata, J. and Blackburn, G.F. (1984) Immunochemical potentiometrisensors. Ann. N. Y. Acad. Sci. 428, 286–292

9 Sidwell, J.S. and Rechnitz, G.A. (1985) Bananatrode – aelectrochemical biosensor for dopamine. Biotechnol. Lett. 7, 419–422

and more attractive. Pioneering work on all these topicswas performed in various labs in Europe, Japan, theSoviet Union, and North America, thus promoting anincreased interest in biocatalysis. For instance, White-sides (Harvard) and his former PhD student Wongreported their results on the in situ NAD(P)(H) cofactorregeneration and on the synthetic exploitation of aldo-lases in 1983. Sih (Madison, WI) and Bryan Jones (Tor-onto, Canada) both exploited enzymatic enantioselectivityfor the synthesis of chiral synthons (for an example see[5]). Klibanov at the Massachusetts Institute of Technolo-gy (MIT) investigated the performances of enzymes inorganic solvents [6].

Enzyme availability was a big issue in those daysbecause biocatalysts could only be isolated from theirnatural and wild type sources. There were no modelingtools, therefore information on enzyme structures couldonly be obtained from time-consuming X-ray diffractionanalysis of protein crystals. Improvement of enzymaticprotein stability, selectivity, and activity could only be

plastic electronics could make biosensors as common athe RFID tag and diverse applications in pharmaceuticascreening, food safety, environmental monitoring, defence

Special Issue: Celebrating 30 years of biote

1983–2013: the long wave

Sergio Riva

Istituto di Chimica del Riconoscimento Molecolare (ICRM), CN

Biocatalysis is the use of enzymes – isolated or in wholecells – in organic synthesis, mainly for the conversion onon-natural substrates. In 1983, biocatalysis offered youngresearchers, previously trained in synthetic and bioorganichemistry, the fascinating promise of being able to exploinature efficiency and selectivity.

What was the state of the art 30 years ago? The 12Principles of Green Chemistry were not yet consideredand ‘biocatalysis’ as a word was not popular as well. Byperforming a Scopus search only four articles on biocatalysis appear in 1983, whereas, in comparison, 1533 resultare documented in 2011. Nevertheless, researchers in thescientific areas of biochemistry/enzymology and organichemistry were getting closer and starting to share theiexpertise [1]. Investigations performed in previous yearhad shown that it was possible to immobilize enzymes andwhole cells on or inside solid supports, in order to improvetheir stability and to allow their recycling [2]. It was alsoknown that organic cosolvents could be used to improvesubstrate solubility, and enzymes retained their catalytiactivity in biphasic systems [3]. As another example, theability of some enzymes to catalyze different reactions had

Corresponding author: Riva, S. (sergio.riva@icrm.cnr.it).

0167-7799/$ – see front matter � 2012 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.tibtech.2012.10.002 Trends in Biotechnology, March 2013,

Vol. 31, No. 3

nology

f biocatalysis

Via Mario Bianco 9, 20131 Milan, Italy

been already observed [4]. Today this property is called‘enzyme promiscuity’. Investigation of the broad substratespecificity of several enzymes as well as their unexpectedperformances in non-aqueous media was becoming more