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Accelerate Your AI-Driven
Drug Discovery: From
Sequence to Validated
Binders in a Single Day
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While AI can design proteins in minutes, traditional cell-based wet-lab validation takes weeks. Integrating cell-free protein synthesis (CFPS) with surface plasmon resonance (SPR) overcomes this bottleneck by allowing rapid screening directly from unpurified extracts. This synergy condenses the “build-test” cycle to a single day, delivering the high-quality data needed to continuously retrain generative AI models.
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To demonstrate the tight integration of upstream expression and downstream screening, Sino Biological’s XPressMAX™ CFPS Kit (Cat#: CFKIT02) was combined with Cytiva’s Biacore SPR technology in an integrated workflow for AI-designed binder validation.
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Why CFPS + SPR for AI Binder Validation
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Rapid Parallel Synthesis
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Enables the synthesis of hundreds of distinct AI-designed VHH (nanobody) variants in parallel.
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Hours, Not Weeks
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Leveraging the high translational efficiency of the XPressMAX™ system, the synthesis phase can be completed in merely 3 hours.
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Purification-Free Screening
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Crude lysates can be directly injected into the SPR biosensor using a His-capture methodology.
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Instant Results
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The downstream SPR system enables rapid screening of large numbers of variants and efficient identification of positive binders.
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Verified Fidelity
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CFPS-derived binders show binding activity comparable to cell-expressed counterparts, with reliable SPR kinetics and affinity data.
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Faster AI Iteration
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Rapid wet-lab feedback supports faster iterative optimization of AI-designed binders.
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Empirical Validation: A High-Throughput Case Study
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In a collaborative case study, Sino Biological and Cytiva combined XPressMAX™ CFPS with Biacore SPR to validate 200 AI-designed VHHs. Expression was completed in 3 hours, followed by purification-free SPR screening of all 200 candidates in 4.5 hours, identifying 11 positive hits.
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Workflow of Ultra-Fast, High-Throughput Screening with CFPS & SPR
Purification-Free Samples, Screening in within 1 day
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To further assess the reliability of this purification-free approach, binding affinity was compared across four distinct sample preparations. The highly consistent results support comparable binding performance across sample formats and reliable direct SPR analysis of CFPS supernatants.
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Comparison of Affinity Values Obtained by SPR
Crude Supernatants from CFPS vs. Purified Samples from CFPS/CHO
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Sample
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KD (M)
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Y19
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Y2
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Y12
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Linear Template-Derived Crude Supernatant (CFPS)
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6.30E-10
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6.22E-11
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1.22E-09
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Plasmid Template-Derived Crude Supernatant (CFPS)
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7.14E-10
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8.06E-11
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2.71E-09
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Purified Sample (CFPS)
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7.65E-10
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5.70E-11
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1.67E-09
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Purified Sample (CHO)
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6.92E-10
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9.94E-11
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9.76E-10
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Don’t Miss Out!
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