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Over the past decades,there have been significant efforts devoted to explore the use of nanoparticles(NPs)in the fields of biology and medicine.Several different types of NPs have successfully made their ways into pre‐clinical studies,clinic trials or even successful commercial products used in routine clinical practice.However,there remains an imperious desire for developing novel synthetic approaches in order to produce new‐generation NPs which have(ⅰ)controllable sizes and morphologies,(ⅱ)low toxicity,compatible immunogenicity and in vivo degradability,and(ⅲ)proper surface charges and chemistry for improved physiological stability and longer circulation time.Moreover,multiple functions for example,reporter systems for real‐time monitoring with imaging technologies(i.e.,optical imaging,magnetic resonance imaging and positron emission tomography),targeting ligands for disease‐specific delivery,and controllable mechanism for packaging and releasing of loads will be conferred to individual NPs for conducting multiple applications in parallel.We have recently developed a programmable synthetic approach for preparation of multifunctional supramolecular NPs(SNPs)from different molecular building blocks and loads(i.e.,gene,proteins,drugs,reporter systems and their combinations).A diversity of SNPs with variable sizes and biological functions were prepared by simply mixing the molecular building blocks and loads at different ratios.We have been able to explore the applications of these programmable SNPs for positron emission tomography(PET)and magnetic resonance(MR)imaging,gene delivery,transcription factor delivery,photothermal treatment of cancer cells,as well as targeted drug delivery.Further,it is conceivable that this programmable SNP system would enable the creation of a combinatorial SNP library by manipulating synthetic variables.In order to accelerate screening speed and reduce reagent consumption in search of a small collection of SNPs that exhibit desired biological performance,we designed and fabricated integrated microfluidic chips for performing multiplexed preparation of combinatorial libraries composed of hundreds of different SNP formulations,followed by large‐scale screening.By the end of my presentation,I hope to convince you that,in conjunction with the use of integrated microfluidic screening platform,our programmable SNP system opens up a novel developmental pathway toward new‐generation molecular diagnostics and therapeutics.