Affinity and Kinetics analysis by Label-Free Interaction Biacore technology
Easy-to-use tools for quantitative kinetics and affinity analysis of biomolecular interactions are today indisputable techniques in the development steps of new drugs, as well in a plethora of basic and applied research areas. For example, the selection of the best antibody candidate to meet the requirements of optimal affinity or tightest binding to its target molecule is routinely based on data from label-free detection technologies like surface plasmon resonance (SPR).
The developments of such techniques go back to the 1980-ties, led by Pharmacia Biosensor AB (later renamed to Biacore AB) in Uppsala, Sweden and stimulated then by the ongoing intense research in biosensor technologies as potential new diagnostic tools. The company started its operations in 1985 and after some intense development years succeeded in the launch of its first instrument in 1990. Even if routine diagnostics applications were considered, the techniques developed made it possible to reach the more advanced applications mentioned above. The timely needs for better tools to determine structure and function of biomolecules and the advances in molecular biology in the 1980ies, which made it possible to easily generate large antibody libraries and collections of proteins mutants, were well suited as focus applications for Biacore´s label-free SPR systems.
Critical components to achieve such quantitative data were developed within the company, in particular the 1) miniaturization of the optical SPR detection configuration, 2) microfluidic cartridge for precise sample handling and 3) elaborate surface chemistry on the gold layered sensor. These cornerstones were integrated into a versatile system which became instrumental for the rapid acceptance of the label-free detection principles.
Already from early beginning, applications related to interaction studies of antibodies (or fragments of such) became most widespread. Examples include selections of best combinations for diagnostic assays, reagents for biomarker analysis and most importantly for antibody drug discovery and development. All therapeutics projects in pharma today rely on data from label-free bioanalytical tools like Biacore or similar. Other areas of importance include basic research related to disease areas such as cancer where, for example, detailed studies of cellular signaling cascades can be achieved.
Initially limited to the detection of biomolecules such as proteins and oligonucleotides, the Biacore performance has been continuously refined to facilitate direct detection of the binding of unlabeled low molecular weight drug candidates and even of weak-affinity fragments down to 100 Da in size, with a throughput of >2000 molecules screened/ day . This has opened a new area of use within the drug discovery field. So called “fragment-based drug discovery” has now become an important route for new “small molecule” drug candidates where SPR analysis is one of the most frequently used techniques.
A multitude of data from Biacore analysis in other applications can now be found in the many thousands of articles published since 1990, demonstrating the establishment of the SPR technique alongside other bioanalytical tools like chromatography and MS.
Easy-to-use tools for quantitative kinetics and affinity analysis of biomolecular interactions are today indisputable techniques in the development steps of new drugs, as well in a plethora of basic and applied research areas. For example, the selection of the best antibody candidate to meet the requirements of optimal affinity or tightest binding to its target molecule is routinely based on data from label-free detection technologies like surface plasmon resonance (SPR).
The developments of such techniques go back to the 1980-ties, led by Pharmacia Biosensor AB (later renamed to Biacore AB) in Uppsala, Sweden and stimulated then by the ongoing intense research in biosensor technologies as potential new diagnostic tools. The company started its operations in 1985 and after some intense development years succeeded in the launch of its first instrument in 1990. Even if routine diagnostics applications were considered, the techniques developed made it possible to reach the more advanced applications mentioned above. The timely needs for better tools to determine structure and function of biomolecules and the advances in molecular biology in the 1980ies, which made it possible to easily generate large antibody libraries and collections of proteins mutants, were well suited as focus applications for Biacore´s label-free SPR systems.
Critical components to achieve such quantitative data were developed within the company, in particular the 1) miniaturization of the optical SPR detection configuration, 2) microfluidic cartridge for precise sample handling and 3) elaborate surface chemistry on the gold layered sensor. These cornerstones were integrated into a versatile system which became instrumental for the rapid acceptance of the label-free detection principles.
Already from early beginning, applications related to interaction studies of antibodies (or fragments of such) became most widespread. Examples include selections of best combinations for diagnostic assays, reagents for biomarker analysis and most importantly for antibody drug discovery and development. All therapeutics projects in pharma today rely on data from label-free bioanalytical tools like Biacore or similar. Other areas of importance include basic research related to disease areas such as cancer where, for example, detailed studies of cellular signaling cascades can be achieved.
Initially limited to the detection of biomolecules such as proteins and oligonucleotides, the Biacore performance has been continuously refined to facilitate direct detection of the binding of unlabeled low molecular weight drug candidates and even of weak-affinity fragments down to 100 Da in size, with a throughput of >2000 molecules screened/ day . This has opened a new area of use within the drug discovery field. So called “fragment-based drug discovery” has now become an important route for new “small molecule” drug candidates where SPR analysis is one of the most frequently used techniques.
A multitude of data from Biacore analysis in other applications can now be found in the many thousands of articles published since 1990, demonstrating the establishment of the SPR technique alongside other bioanalytical tools like chromatography and MS.
Written by Stefan Löfås
