Combinatorial Library-Screened Array for Rapid Clinical Sperm Quality Assessment

Nonspecific interactions are ubiquitous and important in biology; however, they are rarely valued or employed in the field of clinical disease diagnosis. Relying on nonspecific cross-interactions, sensor arrays have shown great potential in distinguishing mixtures or nuanced compounds. However, developing generic strategies for constructing effective arrays tailored to compositionally complicated and highly individualized clinical biospecimens remains challenging. Here, we introduce a combinatorial chemistry-screened array strategy, leveraging four-component Ugi reactions to achieve the rapid synthesis of hundreds of structurally diverse sensing elements. Moreover, effective sensor arrays can thus be built by rapidly screening sensors against diverse analytes. Next, we demonstrate the practical applicability of this array by clinical sperm quality assessment, given the current lack of well-established clinical rapid detection techniques. A library of 192 structurally diverse sensor elements was synthesized. Following screening, a pruned 14-element array was successfully constructed, achieving 94.2% accuracy in distinguishing between healthy individuals and four types of abnormal sperm samples from patients within 1 min. This universal strategy avoids complex sensor design and greatly improves the efficiency of sensor array construction, offering a new way of designing effective arrays.