Pooled SPR Screening for High-Throughput Binder Identification
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current high-throughput screening (HTS) methods for identifying compounds capable of binding to biological targets are resource-intensive, time-consuming, and prone to false positives/negatives, and SPR-based methods are limited by low throughput and high costs, making it unsuitable for large compound libraries.
Innovation Solution
A method involving pooling of compounds into samples and using sensor-based assays, specifically surface plasmon resonance (SPR), to identify compounds capable of binding to biological targets or fragments thereof, with a deconvolution analysis to determine binding values.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If high-throughput screening (HTS) is used to screen large compound libraries, then the ability to identify binding compounds is improved, but the method becomes resource-intensive, time-consuming, and expensive
Solution Approach 1:
Multiple individual compound assays are merged into a single pooled sample assay. By combining multiple compounds into one pool and testing the pool as a single unit, the method achieves high-throughput screening capability while reducing the number of individual assays required, thereby saving time and resources.
Solution Approach 2:
The method uses computational deconvolution analysis to create virtual representations of individual compound binding profiles from pooled data. This allows the system to infer individual compound behavior without physically testing each compound separately, effectively copying the information-gathering function at lower cost and time expenditure.
2Productivity
If traditional HTS methods are used, then large compound libraries can be screened, but false positives and false negatives are generated
Solution Approach 1:
The method implements iterative deconvolution analysis where the results from pooled samples feed back into refined identification of individual compound binders. By using the pooled data to inform subsequent analysis rounds, the system continuously improves accuracy and reduces false positives/negatives while maintaining high throughput.
Solution Approach 2:
The compound library is segmented into multiple pooled samples with specific compositions designed to enable mathematical deconvolution. This segmentation strategy allows the system to maintain screening capacity while creating data structures that facilitate accurate identification of true binders through computational analysis.
3Measurement precision
If surface plasmon resonance (SPR) is used for compound identification, then binding accuracy is improved, but throughput is reduced and costs increase
Solution Approach 1:
Multiple SPR assays for individual compounds are merged into a single pooled SPR assay. By injecting a pool of compounds simultaneously through the SPR sensor, the method maintains the high measurement precision of SPR technology while achieving throughput comparable to traditional HTS, as the sensor surface is utilized more efficiently.
Solution Approach 2:
The SPR sensor surface is designed to handle multiple functions: it can detect binding signals from pooled compounds, provide reference signals from control samples, and enable deconvolution analysis all within the same instrument run. This multi-functionality allows SPR to achieve both high precision and high throughput simultaneously.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach significantly increases the throughput and reduces costs for screening large compound libraries, allowing for accurate identification of compounds with diverse chemical structures and complex binding properties.
Implementation Method 1
surface plasmon resonance (SPR) was introduced as a technique to identify compounds capable of binding to a biological target that is immobilized on a sensor surface. In essence, SPR is based on a change in refractive index upon binding of molecules to the biological target immobilized on a surface. This alteration in the refractive index shifts the resonance angle, which can be measured as a change in the intensity of the reflected light.
Data Source
Figure 1~2
Figure 3~4
AI summary
The present disclosure relates to a sensor-based high-throughput screening method for identifying one or more compounds capable of binding to a biological target or a fragment thereof by high-throughput screening, and a device adapted to carry out said method.