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The maximal procedure is a restricted randomization method that maximizes the number of feasible allocation sequences under the constraints of the maximum tolerated imbalance and the allocation sequence length. It assigns an equal probability to all feasible sequences. However, its implementation is not easy due to the lack of the Markovian property of the conditional allocation probabilities. In this paper, we propose the asymptotic maximal procedure, which replaces the sequence-length-dependent conditional allocation probabilities with their asymptotic values. The new randomization procedure is compared with the original maximal procedure and few other randomization procedures with the maximum tolerated imbalance via simulations and is found to be a practical choice for future clinical trials. [ABSTRACT FROM AUTHOR]

Distance-based microfluidic paper-based analytical devices (μ PADs) are simple and user-friendly detection platforms for disease screening, environment monitoring and food safety. However, the current distance-based μ PADs still face major challenges of relatively low sensitivity and accuracy. In this work, we propose a novel chromogenic reaction-free distance-based (CRFD) μ PAD strategy for sensitive and accurate quantitation of microRNAs (miRNAs) via viscosity amplification and surface hydrophobicity modulations. The CRFD μ PAD with sampling, indicator (with red ink), and detection zones is scaled with reference patterns. Target miRNA in sample is pre-amplified with rolling circle amplification (RCA) reaction to specifically enhance its viscosity. The difference of flow between target and control is further enlarged on CRFD μ PADs whose surface hydrophobicity is rationally modulated by in situ metal-organic frameworks (MOFs) modification. Meanwhile, the repeatability and flow shape are significantly improved. For a proof-of-concept demonstration, the miR-221 and miR-222 in liver cells lysis were sensitively detected by naked-eye with limits of detection of 0.33 and 0.37 pM, respectively. A smartphone-based auto-reading system (SAS) was developed to further improve the accuracy and convenience, showing greatly reduced relative standard deviation (RSD) of assay from 12.2% to 1.0%. This facile and extensible strategy is promising for rapid detection in complex biosystem. [Display omitted] • Distance-based μ PADs without chromogenic reaction are used for microRNA detection. • Viscosity is specifically amplified by RCA to generate the flow distance difference. • Sensitivity is improved by in situ MOF modification that modulate the surface. • A smartphone-based system is developed to improve the accuracy and convenience. [ABSTRACT FROM AUTHOR]