Automated urinalysis

Over the past 25 years, new automated technologies and informatics have greatly reduced the labor intensity of urinalysis, and have created new technical possibilities.

Although dry-chemistry technology for urinary test strips has made limited progress, advances in electronic detection have considerably improved. An interesting recent evolution is the use of smart phones for reading and interpreting urine test strip results. According to the reflectance theory, the reciprocal value of reflectance readings is proportional to the concentration of the measured analyte.

Automated microscopy
In manual microscopy, several steps, such as centrifugation, decantation, and re-suspension, led to cellular lysis and loss. Progress in informatics and computer technology has enabled the development of automated microscopy based on pattern recognition.

Flow cytometry
Urine particle flow cytometers (UFCs) have improved count precision and accuracy, compared with visual microscopy and offer significant labor reduction. Clinical studies using UFCs have focused on diagnosis and monitoring of urinary tract infection; localization of the sites of hematuria; and diagnosis, monitoring, and exclusion of renal disease. Depolarized side-scattered light was introduced to improve crystal sensitivity and to better discriminate between RBCs and crystals; however, in contrast to microscopy-based readers, differentiation of crystals is not possible. The most popular approach is to combine test strips with UFCs for primary screening, using both methods (i.e., UFC and strips). The implementation of such a strategy significantly reduces microscopy review and saves time and cost without diminishing clinical utility. With UF-1000i, bacteria forward scatter (B_FSC) and fluorescent-light scatter (B_FLH) can be used for preliminary discrimination of urinary tract infections (UTIs) caused by Gram-positive or Gram-negative bacteria. Evaluation of B_FSC and B_ FLH parameters from bacteria histograms can be useful in distinguishing between Gram-negative and Gram-positive bacterial strains. B_FSC data could be useful in presumptive exclusion of UTIs caused by Gram-positive bacteria. Urine culture is considered the gold standard for UTI diagnosis. It can determine the level of bacteriuria and antimicrobial susceptibility. However, there is no standardized bacterial count indicating significant bacteriuria, applicable for all types of UTIs. Because of the high percentage of negative results (up to 60%) depending on the setting, there is a need for an efficient screening method, reducing the number of unnecessary culture tests. Several methods for screening-out culture-negative samples have been developed, including dipstick chemical tests (nitrite, leukocyte esterase, urinary protein, and urinary hemoglobin) and manual or automatic microscopic examination of urine sediment (detection of particles, WBCs, and microorganisms). Although these screening methods are primarily used in general practice and microbiology laboratories, they are subjective and time-consuming and demonstrate poor sensitivity and negative predictive value. Using flow cytometry, negative results could be reported earlier, substantially reducing unnecessary empirical antibiotic prescriptions. The use of flow cytometry can reduce the number of urinary samples processed in the clinical laboratory by 28–60%.

Laboratory-on-a-chip
Advances in microfluidics have enabled the development of new chip-based assays, which will alter the field of automated urinalysis in the near future.

Outlook
Over the past two decades, automated urinalysis has undergone remarkable technical progress. Both microscopy- and flow cytometric-based instruments generate reliable results that are clinically useful, and automated test strip reading provides added value. Additional integration of existing technologies may further reduce turn-around times.