The development of new technologies and testing platforms for diagnosis of infectious diseases has changed the protocol for detection of causative organisms of infectious diseases. Advances in technology have improved the testing methods for urinary tract infections (UTIs), as they are more accurate and sensitive, and provide faster outcomes and a broader range of pathogen detection compared with most traditional methods.

Continuous innovations are increasing the performance and speed of clinical/laboratory diagnostics and play an integral part in decision-making while performing a disease test. The increase in infectious diseases and early detection of non-communicable diseases such as UTI, diabetes, kidney stones, or liver disorders are some of the strongest areas within the urinalysis field. The magnitude of the target diseases is immense with the occurrence of millions of new cases every year.

The growing prevalence of these diseases and the introduction of technologically advanced, rapid, non-invasive, and user-friendly tools for urinalysis are estimated to be the major growth drivers of the urinalysis market globally. The development of wireless communication and miniaturized point-of-care (PoC) urinalysis instruments is a boon to the market. These advancements provide single-level access to the results throughout the hospital at the same time. Moreover, introduction of the automated urine sediment analyzers such as digital flow morphology (digital imaging) and fluorescence flow cytometry are responsible for the high growth potential of this market.

Technology Trends

Emerging technologies including biosensors, microfluidics, and other integrated platforms could improve diagnosis via direct pathogen detection from urine samples, rapid antimicrobial susceptibility testing, and PoC testing. The ability of new diagnostic technologies to work directly with urine samples without compromising the sensitivity and specificity of standard methods is paramount.

Additionally, advances in molecular biology have substantially expanded the understanding of microbial genetics enabling detection of pathogens based on their molecular signature. Molecular and proteomic technologies, fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR) have been approved in the past 20 years and are being continuously improved for the diagnosis of bacterial infections. Successful development and implementation of these technologies has the potential to usher in an era of precision medicine to improve patient care and public health.

Automation. Urine collection to pathogen identification typically takes 18–30 hours. After pathogen isolation and identification, antimicrobial susceptibility testing (AST) takes an additional 24–48 hours. Recently, high-throughput and automated instruments have been developed to provide readouts of increased sensitivity, resulting in a modest reduction in turnaround time to approximately 10–16 hours.

Screening assays. Current screening assays include urine dipstick tests, microscopic urinalysis, and urine Gram stain. Urine dipsticks are fast and simple to use, but they have inadequate sensitivity. Microscopic urinalysis and urine Gram staining have also been shown to lack sensitivity and have poor specificity. To address these shortcomings, new screening technologies are in development for rapid and direct screening of urine samples, for example, antibody-based lateral flow assay.

Flow cytometry. Improvements in system integration and automation have resulted in the development of systems that can identify bacteriuria quickly, in as little as 45 minutes. These systems do not provide pathogen identification, but they can include AST. Further attempts are being made to incorporate some speciation information into light scattering techniques, such as differential lysis of Gram-positive and Gram-negative bacteria with sodium dodecyl sulfate, and algorithms to distinguish the light-scattering patterns of bacilli from cocci, but these techniques are still experimental.

Mass spectrometry. Over the years various mass spectrometry (MS) technologies have been developed with varying degrees of analytical performance in terms of mass resolution, reproducibility, selectivity, and sensitivity. The emergence of MS-based proteomic platforms as prominent bioanalytical tools in clinical applications has enhanced the identification of protein-based urinary biomarkers that aid in characterization of pathophysiological mechanisms and the identification of therapeutic targets of kidney and non-kidney diseases.

MALDI–TOF MS. Direct analysis of urine samples using matrix assisted laser desorption ionization-time of flight (MALDI–TOF) decreases the time needed for pathogen identification. The entire process can deliver results within 1–3 hours.MALDI–TOF has improved the workflow for pathogen identification from isolates in clinical laboratories. Also, utilizing MALDI-TOF MS for the identification and characterization of urinary proteins/peptides poses several advantages including reduced analysis time, enhanced detection sensitivity, extensive mass range, enhanced mass resolution when equipped with a reflectron, increased tolerance for contaminants, and molecular imaging capabilities.

FISH technology. The rapid fluorescence in situ hybridization assays can be processed in as little as 20 minutes with sensitivity and specificity of more than 96 percent. FISH technology can be used for rapid, accurate identification of pathogens; however translation of FISH to a point-of-care diagnostic could be challenging, limiting its widespread application.

Multiplex PCR. The sensitivity and specificity of PCR that enables the detection of rare targets has assisted its adoption in to clinical diagnosis applications. A role for PCR for direct-from-urine UTI diagnostics is being investigated by several companies that have developed systems for
PCR-based detection of pathogens.

Micro-technologies. Advances in micro-technologies and nanotechnologies have resulted in the development of biosensors with integrated microfluidic handling systems capable of performing the complex molecular assays that are required for the detection of pathogens in biological matrices.

Integrated biosensor–microfluidic platforms have the most potential for point-of-care testing, as they facilitate direct urine analysis and can encompass all assay steps in a compact device. Biosensor or microfluidic systems capable of integrated pathogen identification and AST might provide the greatest clinical benefit for complicated UTI.

Particle recognition system. As the urine specimen passes through the analyzer, a camera captures up to 500 frames per specimen. Each image is classified by size, shape, contrast, texture features automatically. This new technology in the field of urology has shown to be more reliable for identifying cellular components.

Road Ahead

Most developments till date have been targeted toward decreasing the turnaround time and enhancing automated processing in the clinical laboratory, either to improve the yield of the screening assays, thereby reducing the workload of processing negative urine samples, or to improve the throughput for batch processing, as urine is the most common clinical sample. Adaptations of MALDI-TOF, FISH, and multiplex PCR for urinalysis are the best route to expedite uropathogen identification in short period of time. Biosensors and microfluidics provide great promise for development of new diagnostic tools. Integrated technology platforms that can be deployed at either point of care or in a clinical laboratory and can provide timely diagnostic information (within 3 hours) to direct personalized antibiotic treatment in the are highly desired.

Substantial improvements in sensitivity and specificity have also been achieved, but the commercialization of biosensors for infectious diseases is still in its infancy. As new technologies gain acceptance for complicated UTIs, the benefits to a wider patient population and public health can be determined. To fully realize the benefits, the many stakeholders in the healthcare system including physicians, hospitals, clinical microbiology laboratories, insurance companies, and biotechnology companies must coordinate to facilitate implementation of rapid UTI diagnosis. As scientific knowledge of host-pathogen interactions increases, the next generation of point-of-care diagnostics could be refined to analyze the host response biomarkers to further assess the appropriate course of treatment.

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