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Background The production of bispecific antibodies (bsAbs) at the discovery stage poses challenges in throughput, yield, and purity, particularly for true four-chain (TFC) bsAbs containing two distinct LCs, due to the high risk of chain mispairing. The TFC Quick ‘n’ Clean platform, based on the WuXiBody™ format, addresses these challenges by ensuring correct LC-HC pairing and enabling high-throughput, high-purity production of four-chain bsAbs.Methods In the WuXiBody™ format, the CH1/CL domain of one parental mAb was replaced with the TCR constant domain to prevent LC mispairing. Two bsAb formats were designed: In the double-tagged format, His and Flag tags were incorporated to enable tandem affinity purification; In the non-tagged format, FcRn-null mutations were introduced into the Fab-arm Fc region, and codon optimization was applied to reduce TCR-arm expression, thereby ensuring the selective overexpression of Fab-arm-related byproducts. Then, codon-optimized constructs were cloned into proprietary vectors and transfected into CHO cells. Cultures were harvested on day 7. HCCF was purified via tandem purification workflows: Ni-Anti-DYKDDDDK-SEC for double-tagged bsAbs and ProA-SEC for non-tagged bsAbs. Final products were analyzed by SDS-PAGE, SEC-HPLC, Intact Mass analysis, and LAL assays.Results A total of 30 bsAbs were successfully produced in both double-tagged and non-tagged formats from 20 mL CHO cultures within 3-4 weeks, each yielding >1 mg. For the 15 double-tagged bsAbs, tandem purification workflow effectively removed homodimers and half-antibodies, achieving >99% heterodimer purity. The 15 non-tagged bsAbs also reached >99% heterodimer purity by eliminating Fab-arm-related byproducts through ProA-SEC purification. Intact Mass analysis confirmed correct heterodimer assembly for all constructs. Additionally, all final products exhibited endotoxin levels <0.1 EU/mg.Conclusions TFC Quick ‘n’ Clean is the first high-throughput production platform for true four-chain bsAbs in both double-tagged and non-tagged formats, consistently achieving >1 mg yields and >99% heterodimer purity. This innovative platform facilitates rapid, cost-efficient identification of optimal bsAb pairings in early-stage drug discovery.