A multiple-ligand approach to extending the dynamic range of analyte quantification in protein microarrays

Andersson, Olof; Nikkinen, Henrik; Kanmert, Daniel; Enander, Karin

doi:10.1016/j.bios.2008.12.030

Cited by 19 publications

(23 citation statements)

References 25 publications

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“…Perhaps the simplest of these to conceive is the use of sets of receptors differing in affinity to broaden the dynamic range (Figure 7A), an approach that nature employs in many naturally occurring systems 36 and that several groups have previously applied to artificial biosensors. 37–39 These prior examples, however, generated their receptor variants via binding-site mutations that cause the specificity of the sensor to change as a function of target concentration, a problem that the population-shift mechanism circumvents.…”

Section: Broadening and Shaping The Dynamic Range Using Matched Recepmentioning

confidence: 99%

Using Nature’s “Tricks” To Rationally Tune the Binding Properties of Biomolecular Receptors

Ricci

Vallée‐Bélisle

Simon³

et al. 2016

Acc. Chem. Res.

132

131

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CONSPECTUS The biosensor community has long focused on achieving the lowest possible detection limits, with specificity (the ability to differentiate between closely similar target molecules) and sensitivity (the ability to differentiate between closely similar target concentrations) largely being relegated to secondary considerations and solved by the inclusion of cumbersome washing and dilution steps or via careful control experimental conditions. Nature, in contrast, cannot afford the luxury of washing and dilution steps, nor can she arbitrarily change the conditions (temperature, pH, ionic strength) under which binding occurs in the homeostatically maintained environment within the cell. This forces evolution to focus at least as much effort on achieving optimal sensitivity and specificity as on achieving low detection limits, leading to the “invention” of a number of mechanisms, such as allostery and cooperativity, by which the useful dynamic range of receptors can be tuned, extended, narrowed, or otherwise optimized by design, rather than by sample manipulation. As the use of biomolecular receptors in artificial technologies matures (i.e., moves away from multistep, laboratory-bound processes and toward, for example, systems supporting continuous in vivo measurement) and these technologies begin to mimic the reagentless single-step convenience of naturally occurring chemoperception systems, the ability to artificially design receptors of enhanced sensitivity and specificity will likely also grow in importance. Thus motivated, we have begun to explore the adaptation of nature’s solutions to these problems to the biomolecular receptors often employed in artificial biotechnologies. Using the population-shift mechanism, for example, we have generated nested sets of receptors and allosteric inhibitors that greatly expanded the normally limited (less than 100-fold) useful dynamic range of unmodified molecular and aptamer beacons, enabling the single-step (e.g., dilution-free) measurement of target concentrations across up to 6 orders of magnitude. Using this same approach to rationally introduce sequestration or cooperativity into these receptors, we have likewise narrowed their dynamic range to as little as 1.5-fold, vastly improving the sensitivity with which they respond to small changes in the concentration of their target ligands. Given the ease with which we have been able to introduce these mechanisms into a wide range of DNA-based receptors and the rapidity with which the field of biomolecular design is maturing, we are optimistic that the use of these and similar naturally occurring regulatory mechanisms will provide viable solutions to a range of increasingly important analytical problems.

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Section: Broadening and Shaping The Dynamic Range Using Matched Recepmentioning

confidence: 99%

Using Nature’s “Tricks” To Rationally Tune the Binding Properties of Biomolecular Receptors

Ricci

Vallée‐Bélisle

Simon³

et al. 2016

Acc. Chem. Res.

132

131

View full text Add to dashboard Cite

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“…Moreover, the affinity towards the analyte of the chosen ligand can be used to tune the dynamic range of the assay [35]. Thus, a careful selection of an antibody ligand that addresses both affinity towards protein G and the analyte is important for the performance of the assay.…”

Section: Biosensor Surface Designmentioning

confidence: 99%

Orientation and capturing of antibody affinity ligands: Applications to surface plasmon resonance biochips

Bergström

Mandenius

2011

Sensors and Actuators B: Chemical

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A surface plasmon resonance (SPR) sensor chip with immobilized protein G was used for simultaneously capturing, purifying and orienting antibody ligands. The ligands were further stabilized by chemical cross-linking. This procedure of designing the sensor chip improved efficient use of the ligands and could prolong the analytical use.The procedure was evaluated on standard dextran-coated sensor chips onto which commercial semi-purified antibodies toward human serum albumin and human troponin where captured and used for analysing their antigens.The procedure demonstrates a general design approach for presenting the biorecognition element on a biosensor surface which enhances sensitivity, stability and selectivity at the same time as an impure ligand is purified.

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“…The only approaches that have been reported to date to broaden the dynamic range of a biosensor, however, has employed receptors varying in affinity via alterations of the binding site itself 12–15 , which also affects specificity, Sensors made by combining such receptors therefore exhibit varying specificity across their dynamic range. We have circumvented this by generating receptors that retain identical specificities whilst varying significantly in affinity.…”

mentioning

confidence: 99%

Engineering Biosensors with Extended, Narrowed, or Arbitrarily Edited Dynamic Range

Vallée‐Bélisle

Ricci

Plaxco³

2012

J. Am. Chem. Soc.

138

205

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Biomolecular recognition has long been an important theme in artificial sensing technologies. A current limitation of protein- and nucleic acid-based recognition, however, is that the useful dynamic range of single-site binding typically spans an 81-fold change in target concentration, an effect that limits the utility of biosensors in applications calling for either great sensitivity (a steeper relationship between target concentration and output signal) or for the quantification of more wide-ranging concentrations. In response, we have adapted strategies employed by nature to modulate the input-output response of its biorecognition systems to rationally edit the useful dynamic range of an artificial biosensor. By engineering a structure-switching mechanism, we first generated a set of receptor variants displaying similar specificity, but spanning a wide range of target affinities. We then rationally combined sub-sets of these variants to expand the pseudo-log-linear dynamic range of our biosensor to six orders of magnitude. Using other combinations of variants we have also fabricated more elaborate, three-state dose-response sensors that respond sensitively only when the target concentration falls above or below some well-defined intermediate regime. Finally, by combining signaling and non-signaling receptor variants, we have succeeded in both compressing the dynamic range of our biosensor by an order of magnitude, and in rationally tuning its narrowed threshold response to any arbitrarily selected target concentrations. Given their widespread occurrence in nature, it would appear that these same approaches could significantly enhance the performance of many biomolecule-based technologies.

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A multiple-ligand approach to extending the dynamic range of analyte quantification in protein microarrays

Cited by 19 publications

References 25 publications

Using Nature’s “Tricks” To Rationally Tune the Binding Properties of Biomolecular Receptors

Using Nature’s “Tricks” To Rationally Tune the Binding Properties of Biomolecular Receptors

Orientation and capturing of antibody affinity ligands: Applications to surface plasmon resonance biochips

Engineering Biosensors with Extended, Narrowed, or Arbitrarily Edited Dynamic Range

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