The authors have developed a rapid and simple method for the small-scale purification of nucleic acids (NA) from clinical specimens such as human serum and urine. The method utilizes the lysing and nuclease-inactivating properties of guanidinium thiocyanate (GuSCN) and the nucleic acid-binding properties of silica particles or diatoms. By using size-fractionated silica particles, the method can purify various types of NA, including covalently closed circular, relaxed circular, and linear double-stranded DNA, single-stranded DNA, and rRNA, from 12 different specimens in less than 1 hour. The purified NA is recoverable in the initial reaction vessel and is suitable for further enzymatic modifications. The method is inexpensive, requires no specialized equipment, and minimizes the risk of pathogen transmission between samples. The authors demonstrate the effectiveness of the method through a series of experiments, including the purification of NA from human serum, urine, and cell-rich sources, such as pathogenic gram-negative bacteria. The method is particularly useful for clinical microbiology applications, where rapid and reliable NA purification is essential.The authors have developed a rapid and simple method for the small-scale purification of nucleic acids (NA) from clinical specimens such as human serum and urine. The method utilizes the lysing and nuclease-inactivating properties of guanidinium thiocyanate (GuSCN) and the nucleic acid-binding properties of silica particles or diatoms. By using size-fractionated silica particles, the method can purify various types of NA, including covalently closed circular, relaxed circular, and linear double-stranded DNA, single-stranded DNA, and rRNA, from 12 different specimens in less than 1 hour. The purified NA is recoverable in the initial reaction vessel and is suitable for further enzymatic modifications. The method is inexpensive, requires no specialized equipment, and minimizes the risk of pathogen transmission between samples. The authors demonstrate the effectiveness of the method through a series of experiments, including the purification of NA from human serum, urine, and cell-rich sources, such as pathogenic gram-negative bacteria. The method is particularly useful for clinical microbiology applications, where rapid and reliable NA purification is essential.