Anal Bioanal Chem (2003) 377 : 434–445

DOI 10.1007/s00216-003-2158-9

REVIEW

Antje J. Baeumner

Biosensors for environmental pollutants and food contaminants

Received: 21 May 2003 / Revised: 25 June 2003 / Accepted: 4 July 2003 / Published online: 12 August 2003
© Springer-Verlag 2003

Abstract This review article provides an overview of the 4], food safety [5, 6, 7, 8, 9], the detection of specific an-
most recent literature on biosensors for environmental alytes in environmental settings [10, 11, 12, 13, 14], and
pollutants and food contaminants. Due to the large num- regarding commercial biosensors [15, 16, 17]. Also, gen-
ber of publications, only papers published between 2000 eral review articles about biosensors with specific empha-
and January 2003 were considered. Also, while not all of sis on food and environmental control have been pub-
the published literature could be reviewed here, over 200 lished [18, 19, 20, 21]. This current review will only ad-
references are cited to provide a good overview of research dress publications from 2000 to January 2003 and will not
undertaken in the last two years. Older publications are cover earlier published papers so as to give a most up-to-
covered by a number of earlier review articles. This arti- date review on the current literature on biosensors for the
cle provides an introduction into the field including spe- detection of food contaminants and environmental pollu-
cific consideration of the application areas, describes the tants. The reader is referred to the aforementioned review
typical biosensor assay format used, and is subsequently articles for pertinent literature prior to 2000. In addition,
structured according to the biorecognition elements used an excellent book by Bilitewski and Turner on biosensors
(i.e., nucleic acids, enzymes, whole cells, tissue and whole for environmental monitoring was published in 2000 [22].
organisms, antibodies and receptors, and biomimetic ma- This article is structured according to biorecognition
terials). In addition, a section on microbiosensing systems elements used in the biosensor systems. Sections are
is provided. Since only very few microbiosensors with ap- based on nucleic acid, enzyme, whole cell, tissue/whole
plications in environmental and food systems have been organism, immunoglobulin or receptor, and also bio-
published, enabling technology is also covered in this ar- mimetic recognition elements. Their applicability to food
ticle. and environmental detection is discussed and examples of
current publications are given. Special emphasis is given
Keywords Biosensor · Environmental analysis · Food at the end of the article to microbiosensors and nanobiosen-
contaminants · Microfabrication sors based on similar detection principles, since these will
play a major role in bioanalytical detection in the future.
Abbreviations BOD biological oxygen demand ·
Biosensors for the detection of food contaminants and
cfu colony forming units · DNP dinitrophenol ·
environmental pollutants have similar requirements of sen-
GFP green fluorescent protein · NASBA nucleic acid
sitivity, limit of detection, and stability as those used in
sequence-based amplification · PCR polymerase chain
medical applications. However, the significantly more com-
reaction · ppt parts per trillion · QCM quartz crystal
plex matrices, the need for large sample analysis, the re-
microbalance · SPR surface plasmon resonance
quired ruggedness, and the need for continuous monitor-
ing in remote places make these sensors even more chal-
Introduction lenging in respect to development of principles and even
more so to their application. With the heightened level of
Many review articles have been published in recent years awareness for pathogenic organism and toxin detection in
discussing the use of biosensors for food analysis [1, 2, 3, respect to biosafety and biosecurity, the field of pathogen
analysis will expand tremendously in the next few years
with applications not only to medical diagnostics but even
more to environmental control and food safety. Also, a
A. J. Baeumner (✉)
Department of Biological and Environmental Engineering,
boost in biosensor application in food and environmental
Cornell University, Ithaca, NY, USA analysis for other types of analytes such as small chemi-
e-mail: [email protected] cals, proteineous toxins, allergens, etc. can be expected,
 435

and very exciting years should be ahead of us with the fur- erature when comparing different technologies. This re-
ther integration of material sciences, microfabrication, view article does not include an extensive description of
and electrical engineering with biosensor technology. sample preparation for the biosensor analysis in food and
Some detection limits reported in recent literature ap- environmental matrices, since this is not within the scope
proach single-cell levels, femtomolar concentration, ppt, or of the article. The reader is referred to the specific litera-
even lower. It is questionable, however, as to which levels ture of sample preparation. However, a couple of interest-
of detection are essential for the assessment of the safety ing examples are provided in the microbiosensor section.
of our food and environment. It is the task of risk assess- It should be pointed out, that bioanalytical systems or
ment analyses to provide direction for requirements of de- biosensor systems are reviewed in contrast to the more re-
tection limit. Our safety should not simply be judged stricted class of biosensors as defined by IUPAC [26], in
based on the possibilities of our new detection technology. which biosensors have to be reusable systems in which
Aside from statistical significance of single-cell and sin- the biorecognition element is in intimate contact with the
gle-molecule analysis, the pathogenic or toxic effect needs transducer element. Especially in light of current mi-
to be taken into account when deciding on detection lim- crofluidic integration with biosensor analysis, the latter
its required of our analytical tools. Prominently, this topic part is most often redundant. In addition, single-to-use de-
has been addressed with biosensors detecting the bioavail- vices might be the best choice for systems that can detect
ability of toxins and pollutants in environmental samples, as little as ten or fewer cells or molecules per sample,
rather than total concentrations present, and a few biosen- since cross-contamination by different samples would re-
sors are cited addressing this point [23, 24, 25]. sult in significant problems with reusable biosensors.
Sample preparation is typically an integral part of each
chemical and biological analysis, and is most important
for food and environmental analysis. The analytes either Assay formats
have to be made accessible (such as intracellular compo-
nents of food pathogens), have to be concentrated from large In general, three different assay formats are used in bio-
volumes (typically air or water), or have to be separated from sensors – the direct and the indirect format, the latter one
inhibiting components of the sample matrix, such as lipids, either as a competitive or non-competitive assay. In the
inhibitors to enzymatic reactions, humic acids, complex- case of the direct assay (Fig. 1), the analyte is bound by its
ing agents, etc. These preparation steps can be as simple biorecognition element, which is detected directly. This
as particle size filtration or organic solvent extraction, or can be an antigen binding to its antibody, a hormone bind-
as complex as molecular biological amplification of nucleic ing to a receptor, a substrate reacting with its enzyme and
acid sequences using polymerase chain reaction (PCR) or producing a product. The detection of these binding events
nucleic acid sequence-based amplification (NASBA). The is limited to the event itself and can be changes in mass,
time required for these reactions should be calculated into refractive index, impedance, pH, etc.
the overall analysis time; however, most publications only In contrast, in the indirect format, an additional reac-
report the time required for the bioanalysis itself, some- tion has to occur in order to detect the binding of analyte
times describing minute-long assays that follow hours of and biorecognition element. This additional reaction can
sample preparation. Therefore, the reader is advised to care- either be competitive (Fig. 2) or non-competitive (Fig. 3).
fully investigate the overall detection time reported in lit- In both cases, a label is typically used for subsequent de-

Fig. 1A–D. Direct assay format

of biosensors. A biorecognition
element is immobilized on the
surface of a transducer. Sample
containing analyte and other
components are incubated with
the biosensor (A), the analyte
specifically binds to the bio-
recognition element and a sig-
nal is produced by the trans-
ducer (B). In a second exam-
ple, the sample does not con-
tain the analyte but only other
components (C). No signal is
obtained upon incubation, since
no interaction between the bio-
recognition element and the
other components occurs (D)
436
Fig. 2A–D. Indirect assay for-
mat with competitive binding.
A biorecognition element is
immobilized on the surface of
a transducer. Sample contain-
ing analyte and other compo-
nents are incubated with the
biosensor (A), and a competi-
tor molecule is added to the
mixture to compete with the
analyte for the binding to the
biorecognition element (B).
The signal generated is indi-
rectly proportional to the con-
centration of analyte present in
the sample (B). In a second ex-
ample, the sample does not
contain the analyte but only
other components (C). A com-
petitor molecule is again added
to the mixture (D). Since no
analyte is present, all accessi-
ble sites of the biorecognition
elements will be saturated with
the competitor molecule (D)

Fig. 3A–D. Indirect assay for-

mat with non-competitive
binding. A biorecognition ele-
ment is immobilized on the
surface of a transducer. Sample
containing analyte and other
components are incubated with
the biosensor (A), and a sec-
ond biorecognition element
with a label is added to the
sample to bind to the analyte
(B). The signal generated is di-
rectly proportional to the con-
centration of analyte present in
the sample (B). In a second ex-
ample, the sample does not
contain the analyte but only
other components (C). A sec-
ond biorecognition element
with label is again added to the
mixture (D). No signal is ob-
tained

tection and quantification. The detection scheme is much user with the more desirable low signals for low concen-
less limited than in the case of the direct approach and de- trations and high signals for high analyte concentrations.
pends on the nature of the label. This label can be optical, Environmental and food biosensors do not differ with
electrochemical, or mass related and thus permits the use respect to their assay format from biosensors in other ap-
of any transduction principle with indirect assay formats plication areas. However, the complexity of sample matri-
in contrast to the constraints given by the direct assay, ces often suggests the use of indirect assays to avoid false
which is limited by the nature of the analyte itself. positive and false negative signals, since labels and detec-
Direct assays and non-competitive indirect assays yield tion mechanisms can be applied that will have the least in-
signals directly proportional to the analyte concentration, terference with the nature of the sample matrix.
whereas the competitive indirect assay provides an indi-
rect proportionality. This disadvantage can be compen-
sated by data software analysis, which can provide the
 437

such as the surface plasmon resonance (SPR) DNA biosen-

Nucleic acid-based biosensors sor described by Feriotto et al. for the detection of Round
up ready soybeans in which PCR-amplified sequences from
Most nucleic acid biosensors are based on the highly spe- transgenic and wild-type soybeans were investigated for
cific hybridization of complementary strands of DNA and evaluation of the SPR sensor principle [37].
also RNA molecules. In addition, toxicity tests based on Several articles were recently published under the rubric
the interaction of toxic compounds with DNA molecules of DNA biosensors for environmental monitoring and toxic
have been developed especially for environmental moni- compound detection. An interesting article by Lu et al. in-
toring and toxicity screening assays. In an earlier review vestigates the use of catalytic RNA and DNA for the de-
by Mascini et al. [27] DNA biosensors were described in- tection of metals and their potential application in envi-
cluding biosensors for toxicity screening, PCB and afla- ronmental and pharmaceutical fields [38]. Mecklenburg et
toxin detection with specific discussion of application to al. analyzed 27 different metals ranging from Ag to Zn
food and environmental samples, and an extensive review with a DNA-based sensor in the effort to develop broad-
by Wang focused on DNA biosensors based on hybridiza- range sensing elements for environmental analysis [39].
tion and small molecule–DNA interaction biosensors for Chiti et al. described a chronopotentiometric DNA biosen-
environmental monitoring [28]. Olsen presented a review sor for amine detection. The sensor was able to quantify
on DNA detection technology for pathogenic organisms concentrations of those molecules with two or more aro-
in food; while not focusing on biosensors, it summarized matic rings in the submicromolar range after only two
good examples of the potential use and limitations of nu- minutes of accumulation. Wastewater samples were tested
cleic acid biosensors in food analysis [29]. and biosensor signals compared favorably with classical
Improvement of the immobilization of DNA probes genotoxicity tests like the Toxalert 100 based on biolumi-
onto transducer surfaces has been reported by Tombelli et nescence signals [40, 41].
al. [30] and Ryu et al. [31]. Specific efforts are reported to In a similar approach, Oliveira-Brett et al. utilized a
decrease the likelihood of non-specific binding to the DNA biosensor for the detection of pesticides using ten
transducer surface of piezocrystals which is one of this derivatives of the 1,3,5-triazine herbicides as model ana-
transducer’s major drawbacks in application with com- lytes. A time-dependent interaction of all herbicides with
plex matrices. the immobilized DNA was observed with the electro-
The detection of bacteria and other pathogens in food, chemical sensor [42]. Genotoxicity sensors should thus be
drinking water, and air based on their nucleic acid se- considered alternatives to the classical and more involved
quences has been explored using quartz crystal microbal- genotoxicity tests and will simplify the analysis of large
ances (QCM) and optical detection systems. Mo et al. [32] numbers of samples.
reported the detection of a few E. coli cells per 100 mL of
water combining the detection of the lac gene with PCR
amplification and QCM detection. Baeumner et al. [33] Enzyme-based biosensors
detected as few as 40 E. coli cells per 1-mL sample using a
simple optical dipstick-type biosensor coupled to NASBA, Enzyme-based biosensors represent a much larger group
emphasizing the fact that only viable cells are detected of sensors in the environmental and food applications than
and no false positive signals are obtained from dead cells nucleic acid biosensors. More than 80 articles were pub-
present in a sample, which is important in respect to lished in the last couple of years about enzyme sensor ap-
safety and also food and environmental sample steriliza- plications in these areas. Of environmental issues studied,
tion assessments; similarly, a biosensor for the protozoan biosensors focused on environmental monitoring and pes-
parasite Cryptosporidium parvum was developed [34]. ticide detection in particular was the topic of highest in-
DiGiovanni [35] investigated the Dupont 96-well BAX terest in food applications.
PCR system that is based on the melting curve properties Improvements to enzyme biosensors in general and with
of PCR products for the detection of C. parvum in spiked respect to environmental and food applications were de-
water samples exhibiting a similarly low detection limit as scribed by several authors. Electrochemical interfaces to
obtained with the one described by Baeumner et al.. enzymes [43, 44], application of quinoproteins [45] and
Tombelli et al. described the development of a DNA metalloproteins [46], investigations on immobilization and
piezoelectric biosensor for the detection of bacterial toxi- encapsulation [47], studies on potential enzyme array sen-
city based on the detection of a PCR amplified gene frag- sors [48], and several applications of enzyme sensors were
ment of Aeromonas hydrophila. The biosensor was applied reviewed previously [49, 50, 51, 52]. While some of these
to vegetables, environmental water, and human specimens. describe the use of enzyme electrodes in food technology
The DNA probes were immobilized on the piezocrystal in general, the design of the sensors can be applied di-
surface using standard biotin–streptavidin binding [36]. rectly to the detection of food contaminants.
The biosensor was able to successfully distinguish be- Papers describing the detection of pathogenic bacteria
tween samples containing the pathogen and those not con- using enzyme-based biosensors were limited. Sensors are
taminated. found for the detection of E. coli O157:H7 and Salmo-
The applications of hybridization-based biosensors can nella typhimurium with a bienzyme electrode in a variety
be found for the detection of genetically modified foods of food samples such as chicken carcass wash water,
438

ground beef, and fresh-cut broccoli [53, 54]. One publica- nity norms [81]. An unusual approach was described by
tion concerning the detection of E. coli in environmental Sarkar, in which proteases are used for the detection of
samples is based on culture-enhanced amperometric and dust particles [82]. Among other environmental monitor-
chemiluminescence principles with detection limits of ing analytes are heavy metals partly also focusing on their
about 10,000 cells per 100 mL of environmental sample bioavailability [83, 84, 85, 86]), and nitrite requiring a de-
within one working day [55]. tection limit of 0.1 mg L–1 in potable water [23].
Pesticides, especially insecticides, have traditionally been In food analysis, the freshness-test based on biogenic
an application area for enzyme-based sensor systems. amines is prevalent and several articles were published
Many of them reach detection limits set forth by govern- based on single or multi-enzyme systems and applied to
mental agencies for environmental samples, infant food, analysis of fish, sauerkraut etc. [87, 88, 89, 90]; others de-
etc., making them attractive alternatives to conventional tect the freshness based on L-lactate detection in tomato
analysis systems. Three review articles give a closer look paste and infant food [91, 92] or by using a continuous
at earlier enzyme-based biosensors [56, 57, 58]. Acetyl- measurement format of enzyme flow reactors. Among other
choline (and butyrylcholine) esterases were used for the articles describing food contaminants, the detection of an-
detection of organophosphates and carbamates either in tibiotics in milk was reported by combining an antibody
single-use devices such as screen-printed electrodes in and enzyme assay approach to determine only active an-
both environmental and food samples [59, 60, 61, 62, 63, tibiotic molecules [93]. A graphite–Teflon–tyrosinase com-
64, 65, 66] for nerve agent detection [67], or in conven- posite biosensor was developed for the quantification of
tional electrochemical systems such as graphite electrodes benzoic acid in mayonnaise and soda drinks [94]. Gly-
[68], or were genetically engineered for more directed coalkaloids were detected using a field-effect transistor as
pesticide analysis. For example, Boublik et al. found that the transducer and butyrylcholinesterase as the biorecog-
while predicting the effect of the mutation was not always nition element [95]. Finally, phytotoxins, especially those
possible, they obtained highly active mutant enzymes; in produced by algae and found in seafood were of interest
one instance the mutant was 300-fold more sensitive to di- [96, 97].
chlorvos than the wild-type enzyme from Drosophila and
288,000 times more sensitive than the one from electric
eel [69]. Devic et al. reported a sub-nM level detection of Whole-cell-based biosensors
anatoxin and the ability to provide highly specific infor-
mation on the type of toxin present using four different mu- Due to their use as genotoxicity and toxicity sensors, bio-
tants [70]. In a different approach, the sample containing sensors based on whole cells as biorecognition elements
potentially organophosphorous pesticides is first treated form the largest group among the publications targeting
using pervaporation and then subjected to the acetylcholine environmental pollutant analysis; much fewer applica-
esterase sensors [71]. This method is applied to dichlor- tions are found for food contaminant detection. Not all of
vos and tested using liquid and solid samples resulting in the published papers will be discussed here, especially in
dynamic detection ranges of 0.05–0.5 mmol L–1 and 0.001– respect to the application of bioluminescence signal gen-
0.04 g kg–1, respectively. Gulla et al. studied the reactiva- eration of genetically engineered bacteria; however, rep-
tion of inhibited enzymes for reusability of the biosensor resentative examples are given.
[72]. Other pesticides of interest for biosensor develop- Good general review articles providing an overview
ment included 2,4 D [73]. about the technology and publications in earlier years can
Environmental monitoring using enzyme biosensors is be found [98, 99, 100], some focusing on specific analytes
described for a variety of pollutants. Earlier review arti- such as heavy metals [101], or on specific techniques, such
cles investigate publications focusing on toxicity testing as surface display [102].
[74] and enzyme biosensors in organic solvents [75]. Freire Genetic engineered bacteria or yeast cells to bear the lux
et al. described the development of a continuous electro- or luc gene operon, expressing luminescence proteins such
chemical sensor for the detection of phenols in environ- as the green fluorescence protein (GFP), and similar tech-
mental matrices [76]; Cowell et al. used screen-printed niques have been investigated for years. Good review arti-
single-use electrodes for the same analyte [77], expanding cles giving an overview of this technology in recent years can
it to biosensor arrays based on the same technology [78]. be found, which focus on hydrocarbon pollutants [103], stress
A new bienzyme detection system approach was sug- [104, 105], or include descriptions of other signal reporter
gested by Lindgren et al., in which monophenolic and di- systems such as bacterial luciferase, insect luciferase, β-ga-
phenolic compounds can be differentiated using peroxi- lactosidase, green fluorescent protein, alkaline phosphatase
dase and cellobiose dehydrogenase [79]. etc. Depending on the genetic engineering approach and the
Toxic gas detection was suggested by several authors. cell type chosen, biosensors specific for one analyte can be
For example, Hart et al. investigated the detection of sul- constructed, or those that exhibit general stress response
fur dioxide in gas streams using screen-printed electrodes such as toxicity and genotoxicity sensors. A few examples
[80], Rosa et al. developed an optical biosensor based on of the different types of biosensors and the different ana-
nitrite reductase for monitoring purposes with a limit of lytes targeted are given in the following discussion.
detection of only 0.93 µM, which is below the admissible With respect to toxicity sensors, those based on either
concentration of 2.2 µM imposed by European Commu- the fusion of the lux operon with fatty acid synthesis [106],
 439

or those based on strains sensitive to a variety of stresses trode was used for the detection of cyanide in fruit brandies
such as DNA, membrane, or oxidative damage have been [127].
reported by Gu et al. [107]. Gu and coworkers used their Much more recently, surface display techniques have
biosensing system for the detection of single chemicals or found application in whole-cell biosensors. Novel surface
mixtures and suggest that it can find application in the proteins are introduced into the outer membrane of bacte-
classification of toxic chemicals in wastewater. Genotoxi- ria generating harmless bacteria with new binding or cat-
city is assessed based on the fusion of GFP with the recA alytic functionalities on their cell surface. These are used
promoter [108]. The ecotoxicity of Cu, Zn, and 3,5-DCP as a biorecognition element or biosorbent material in
was determined using Pseudomonas strains genetically bioremediation processes and are envisioned to be excel-
engineered with the lux operon [109]. Horsburgh et al. de- lent biorecognition elements for biosensors in various ap-
scribed an on-line microbial sensor for the control of wa- plication areas including environmental and food analysis.
ter quality [110]. Excellent review articles on the technology and earlier
With respect to more specific analyte detection or groups publications are available [128, 129, 130]. Examples in-
of analytes, sensors were developed for toluene and re- clude the use of metal-binding polyhistidyl peptides [131]
lated compounds using a GFP-producing Pseudomonas or inserting the fungal cellulose-binding domain into a
strain [24], an E. coli cell with lux operon [111], and sim- Staphylococcus [132] for the binding of divalent metal
ilarly 4-chlorobenzoic acid was detected using the lux ions such as Ni2+ and Cd2+.
operon and a DNA fragment from Arthrobacter species
fused and cloned in E. coli [112]. Fluorene and its degra-
dation products were detected using a genetically engi- Tissue/whole (higher) organism-based biosensors
neered Sphingomonas sp. [113]. Arsenite and arsenate
were determined using the GFP reporter gene [114], and Plants and tissues but also higher whole organisms have
biogenic amines were detected with similar technology been used in some biosensor applications in recent years.
[115]. The effect of metal toxicity was studied using two These range from algae to soybeans and nematodes. The
different bacteria species [116]; mercury [117] and other number of biosensors published in this area is minute in
heavy metals [25] were detected. Herbicides are targeted comparison to other biorecognition elements, but they nev-
using a variety of organisms: Shao et al. developed a bio- ertheless are applicable to almost any type of biological
luminescence sensor using cyanobacteria for the detection system as a biorecognition element in biosensors, and in
of herbicides [118]. The dose–response relationship be- fact might point to a future use of biosensors, that is, their
tween seven commonly used herbicides and four lumines- integration into whole plants and animals rather than be-
cence-based bacterial biosensors was characterized [119]. ing separate devices for monitoring of environmental con-
Similarly, a fingerprinting method was established based ditions.
on metabolic lux-marked bacteria [120]. Kim et al. even Shvetsova et al. suggested the use of soybeans and their
suggest using mammalian cells for endocrine-like charac- electrophysiological response to acid rain and other envi-
teristics of environmental pollutants, since these are more ronmental stress conditions as a potential biosensor sys-
sensitive than the bacterial systems [121]. tem [133] and similarly used it for the detection of car-
Finally, in an attempt to solve one of the major draw- bonyl cyanide 4-trifluoromethoxyphenylhydrazone [134].
backs of metabolic-based signal generation of biolumi- The microalgae Chlorella vulgaris was used for the detec-
nescence bacteria, Mirasoli et al. developed a bacterial tion of heavy metals by immobilization of the cells onto a
sensor with an internal correction mechanism of the ana- bundle of optical fibers and detection of alkaline phosphatase
lytical response by introducing an additional reporter gene activity [135], and plant tissue cultures for the same ana-
[122]. lytes are based on the detection of glutathione S-trans-
Genetically engineered microorganisms for non-lumi- ferase activity [136]. Exogenous stress perception in ex-
nescence signal generation was suggested by a number of traterrestrial environments is investigated using trans-
authors. The lacZ gene is one of the most often used. For genic Arabidopsis plants in which the GFP gene is fused
example, Biran et al. developed an electrochemical bio- with the alcohol dehydrogenase promoter [137] and a suc-
sensor for cadmium [123]. cessful monitoring system was established via a growing
Microbial and plant cell biosensors based on respira- plant. Sweet potato tissue was immobilized in a graphite
tory detection are suggested especially for wastewater electrode as peroxidase source and utilized for the detec-
analysis. A good review of earlier published microbial tion of hydrazine in boiler feed water [138]. The use of
systems is given by Riedel et al. [124]. In more recent photosystem II as a complex biorecognition system for the
publications, Dubey et al. suggested the use of Pseudo- determination of herbicides and heavy metals in environ-
monas sp. isolated from corroded metal surfaces for the mental samples was reviewed by Giardi et al. [139].
detection of microbiologically influenced metal corrosion In an unusual approach, Schoening et al. integrated in-
and developed an amperometric biosensor [125]. Cam- sect chemoreceptors with silicon transistors to detect or-
panella et al. developed a toxicity sensor for estuarine wa- ganic compounds in air [140]. DePomerai et al. suggested
ter monitoring based on cyanobacteria and an amperomet- the use of transgenic nematodes for the detection of envi-
ric transducer [126]. With respect to food analysis, Sac- ronmental stress. Caenorhabditis elegans, carrying lacZ
charomyces cerevisiae immobilized on an oxygen elec- and/or GFP reporter genes under the control of stress-in-
440

ducible heat-shock promoters were also used as biorecog- loid detection [167]. Vibrio cholerae detection via its toxin
nition elements [141]. was suggested by Swanson et al. by combining the natural
receptor for the toxin, the glycolipid GM1, with a fluores-
cence energy transfer optical transducer [168]. Antibiotic
Antibody and receptor-based biosensors and other drug residue analysis in food samples have been
published, such as the detection of penicillin in milk using
Biorecognition elements based on antibody and receptor photometric immunosensors [169], chloramphenicol was
molecules are grouped in this section, since their applica- quantified in bile, urine, and meat [170], a variety of vet-
tion area and functionality are very similar. The analytes erinary drugs, such as clenbuterol and ethinyl estradiol in
targeted in recent years spread over a wide range from an- urine, and enrofloxacin in milk were detected using an
tibiotics in milk to general environmental monitoring to eight-channel surface plasmon resonance immunosensor
heavy metals. Excellent review articles describing the [171], Hassnoot et al. described the use of the Biacore
technology and providing an overview of older publica- system for the identification of gentamicin in milk sam-
tions are given by Hock [142] with respect to environ- ples [172], and compare direct versus competitive strate-
mental analysis, Hassnoot et al. [143], Rogers [144], Bili- gies for (dihydro)streptomycin immunoassays [173].
tewski [145] and Tothill et al. [146], the last two particu- Finally, a few immunosensors were developed for
larly focusing on the application of affinity-based biosen- pathogen analysis, but only some of these exhibited excel-
sor for food analysis. lent detection limits with relatively short analyses times.
An almost traditional application area of immunosen- A biosensor using the quartz crystal microbalance was used
sors is pesticide detection in environmental samples and to detect Salmonella sp. in milk samples with detection
food matrices. Strachan et al. described the use of single- limits around 106 colony-forming units (cfu) mL–1 [174].
chain antibodies for the detection of atrazine, mecoprop, Listeria and Salmonella sp. were detected with a similar
diuron, and paraquat emphasizing their superiority over detection limit by an SPR biosensor [175]. Collagen I was
other bioanalytical systems due to their functionality in used for the detection of E. coli O157:H7 [176]. In a sim-
aqueous and also organic solvents [147]. Setford et al. re- ple but very successful dipstick-type assay, Park et al.
viewed immunosensors for organic-phase detection of en- were able to detect E. coli O157:H7 in food matrices at a
vironmental pollutants [148]. low detection limit of about 1,000 cfu mL–1 without any
2,4-Dinitrophenol (2,4-DNP) was detected as a model enrichment required resulting in a very rapid immunoas-
analyte for dioxin with a detection limit of 0.01 ng mL–1 say that was also applied to complex food samples such as
by using a quartz crystal microbalance as transducer ground beef [177]. An evanescent wave sensor was ap-
[149]. Horacek et al. investigated the effect of organic sol- plied towards the detection of Listeria monocytogenes with
vents on a similar system [150]. A potentiometric biosen- minimal enrichment requirements, although this required
sor for simazine was developed and applied to the analy- about 20 h per analysis [178]. A more sensitive sensor for
sis of foodstuff such as meat extracts, milk, tomatoes, and the detection of pathogens in fresh produce was suggested
cucumbers [151]. A different format was described by by Lin et al. and reached detection limits of 100 cells mL–1
Pulido-Tofino et al. who developed a flow-through im- [179]. O’Brian et al. analyzed biological warfare agents
munosensor for isoproturon that was applied to well water using a bidiffractive grating biosensor [180].
and agricultural foodstuff analysis [152]. Killard et al. de-
scribed an atrazine biosensor in which no separation of la-
beled and unlabeled antigen is required [153]. Biomimetic material-based biosensors
Other environmental pollutants including PCBs are de-
tected using screen-printed electrodes [154], and a short Only very few biomimetic-based biosensor for environ-
review discussing PCBs, triazines, heavy metals, and en- mental and food analyses have been published in recent
docrine-disrupting compounds was published by Xu et al. years. Since their recognition element is not a biologically
[155]. A very successful multi-analyte immunosensor de- derived molecule, the inclusion of biomimetic sensors
veloped by the Naval Research Lab was tested in a variety into the group of biosensors is questionable. However, on
of settings [156, 157, 158] and is available as both a portable the other hand, since they mimic the biological activity of
system and laboratory device. antibodies, receptor molecules, lipid bilayers etc. they are
In food contaminant analysis, sulfonamides [159], tox- applied in exactly the same manner as their biological
ins such as aflatoxin [160], and staphylococcal enterotoxin counterparts. With the improvements in material science
B were target analytes in recent publications. The entero- and engineering, the development of novel nanocompos-
toxin was either detected by employing peptides gener- ite materials and the integration of nanotechnology and
ated by phage display [161], or antibodies in combination bioanalysis, this field is very likely to grow significantly
with a surface plasmon resonance (SPR) transducer [162]. in the coming years and is thus included in this review pa-
An SPR transducer was also used to determine ivermectin per.
in bovine milk samples [163]. Ho et al. developed a flow A review article on molecular imprinted polymers for
injection analysis system for fumonisin B1 and tested it in the detection of antibiotics and pesticides recently gave an
a variety of food stuffs [164, 165, 166]. Glorio et al. sug- overview of earlier articles and basics of the technology
gested a very simple dipstick-type sensor for glycoalka- [181]. An article by Kasemo discussed biomimetic mate-
 441

rials among others with respect to biological surface sci- ometer were developed leading to much lower sensitivities
ences [182]. Among the more recent biomimetic sensors than those obtained with conventional SPR sensors and
suggested for food contaminant and environmental pollu- with a resolution in the micrometer range [194]. Tama-
tant analysis, the detection of ricin is included, for which naha et al. presented a new macro-microfluidics hybrid
the A and B chains were imprinted into organic silane technology for chip-scale biosensors [195] and empha-
polymers and detected using fluorescence [183]. How- sized the ease of fabrication and integration in comparison
ever, no application to environmental or food samples has to standard microfabrication technologies. Brooks et al.
been discussed yet. developed a microsensor in which antibodies were dis-
cretely immobilized on a variety of surfaces, thereby en-
suring a segregation of the biorecognition elements [196].
Microbiosensors and Nanobiosensors Arakelian et al. investigated the influence of the external
environment on microbiosensor performances [197], and
Micro/nanobiosensors (i.e., the integration of nanotech- Xie et al. reviewed the use of micro-thermal transducers
nology, microfluidics, and bioanalytical systems) clearly and mini-channel and multi-channel systems [198].
represent one of the future directions of biosensor research. Listeria innocua was used as a model analyte by
Possibilities seem endless when combining these different Bashir et al. in a microsystem with integrated electronics;
areas and hopes are high to solve many current problems while the detection limit reached 1–50 cells it could only
ranging from sample preparation to real portability, from detect those in a small volume (5 nL) resulting effectively
single-cell/molecule detection to true analytical speed, to in a detection limit of 200,000 cells mL–1 [199]. Craighead
reliability. Many obstacles will have to be overcome in or- et al. suggested the use of a diffraction-based cell detec-
der to fulfill all of these hopes; however, some exciting tion system using antibodies as the biorecognition ele-
examples, typically of subsystems and not complete bio- ment and grating mechanism [200]. A fully automated
analytical sensors, can already be found in the current lit- sample preparation system for pathogenic organism de-
erature. tection was developed by Taylor et al. [201], which in-
Actual applications to food contaminants and environ- cludes bacterial spore concentration via filtration, ultra-
mental pollutants are still rare due to the increased com- sonication for spore lysis, and elution of purified DNA for
plexity involved with these areas and due to the early subsequent detection. The detection of PCR-amplified
stages of the research. Thus, in the following discussion, DNA molecules using an on-chip electrochemical trans-
micro/nanobiosensors with this focus are given together ducer was described by Hodko et al. [202].
with some examples of enabling technology. Three recent Microfabrication technology useful for the fabrication
reviews on this subject are cited: Bossi et al. reviewed the of biosensors for environmental monitoring is discussed
integration of capillary electrophoresis with biosensor by Suzuki using as one example the Clark-type oxygen
technology [184], Schultze et al. discussed the use of elec- electrode as the basis for BOD measurements of waste-
trochemical microsystem and nanosystem technology [185], water [203]. Biran et al. described the development of an
and Varadan et al. discussed the use of stereolithography optical fiber-based biosensor using recombinant bacteria
for the fabrication of microdevices [186]. When compar- for the detection of environmental toxicity [204].
ing different microsystems, and also comparing them to Nucleic acid detection was the focus of a porous sili-
their macro-counterparts, it is advised to carefully read re- con microcavity biosensor by Chan et al. who demon-
sults presented, since often values other than concentra- strated that shifts in luminescence spectra can be corre-
tions are given. A couple of examples are pointed out in lated to concentration differences in DNA [205]. Miller et
the subsequent discussion. al. based the detection of DNA molecules on magnetic
Enabling technologies for future micro/nanobiosensor bead labeling and magnetoelectronic detection [206].
designs that have potential for food and environmental A zeptomol DNA biosensor based on the molecular bea-
analysis include the magnetic capture dot technology sug- con technology is suggested by Wang et al.; a main draw-
gested by Jovanovic et al. in which micro-bioreactors can back of this laser-induced fluorescence system is the tiny
be guided selectively through a device [187]. Klotz- sample volume of only 36 pL which cannot be integrated
buecher et al. described the use of excimer laser ablation well with environmental and food applications [207].
for rapid prototyping of plastic microdevices [188]. The Chen et al. developed a method to identify DNA fragments
immobilization of proteins onto a patterned conducting separated in microchannel electrophoresis based on this
polymer for microarray use was described by Oh et al. [189], same detection technology [208].
and Ivanova et al. presented the use of a carboxylic-rich The improvement of affinity-based biosensors by mi-
polymer for the enhanced immobilization of oligonu- crofabrication technologies was the focus of a paper by
cleotides to be used in micro-PCR [190]. Hofman et al. Abrantes et al.. A surface plasmon resonance transducer
developed an efficient sample delivery system and tested was adapted using microfluidics to analyze small volumes
it with immunoassays on planar waveguides [191]. Mayer and to allow for long contact times [209]. Integrating im-
et al. reported a novel transduction mechanism in which munomagnetic systems with microfluidic channels was
conformational changes of proteins can be monitored by the focus of a paper from Choi et al. resulting in a very
surface-enhanced metal nanocluster resonance [192, 193]. rapid immunosensing system [210]. Micromechanical
Microarrays of SPR elements integrated with an interfer- cantilevers have been proposed as transducer for affinity-
442

based biosensor systems in recent years. Raiteri et al. 4. Guilbault G, Luong J (1994) Food Sci Technol 60:151–172
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