Abstract

Bladder cancer holds the record for the highest lifetime cost on a per-patient basis. This is due to high recurrence rates, which necessitate invasive and costly long-term evaluation methods such as cystoscopy and imaging. Microfluidics is emerging as an important approach to contribute to initial diagnosis and follow-up, by enabling the precise manipulation of biological samples. Specifically, microdevices have been used for the isolation of cells or genetic material from blood samples, sparking significant interest as a versatile platform for non-invasive bladder cancer detection with voided urine. In this review, we revisit the methods of bladder cancer detection and describe various types of markers currently used for evaluation. We detail cutting-edge technologies and evaluate their merits in the detection, screening, and diagnosis of bladder cancer. Advantages of microscale devices over standard methods of detection, as well as their limitations, are provided. We conclude with a discussion of criteria for guiding microdevice development that could deepen our understanding of prognoses at the level of individual patients and the underlying biology of bladder cancer development. Collectively, the development and widespread application of improved microfluidic devices for bladder cancer could drive treatment breakthroughs and establish widespread, tangible outcomes on patients’ long-term survival.

Highlights

  • The human renal system is an exceptional example of biological structure and organization, efficiently filtering waste from the bloodstream while selectively retaining nutrients

  • When an analyte solution containing both bladder cancer cells (HTB-9 human urinary bladder analyte solution containing both bladder cancer cells (HTB-9 grade II carcinoma cell lines) and blood cells was passed through the microfluidic device, cells were captured by the silicon microchannels which served as the trapping gates (Figure 2A)

  • Research into novel cancer detection methods is ongoing in hopes of developing an alternative that surpasses invasive cystoscopy

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Summary

Introduction

The human renal system is an exceptional example of biological structure and organization, efficiently filtering waste from the bloodstream while selectively retaining nutrients. The performance of existing tests varies with a number of factors, including hematuria [18,19], the specific clinician performing the assay [20], and the presence of other bladder conditions [21] These tests tend to have lower sensitivity (proportion of positive test results in which a patient has bladder cancer) with earlier stages of bladder cancer [22,23,24], limiting their ability to detect bladder cancer when treatment is most likely to have a positive outcome. In comparison to the current combination of invasive cystoscopy and slow cytology, robust devices for screening, diagnosis, and monitoring of bladder cancer will expand physicians’ ability to detect cases in early stages when survival rates are highest. The development of effective microfluidic screening and diagnostic methods for bladder cancer will likely lead to improved patient health outcomes, significant cost savings, and efficient use of clinical resources. Of a screening or diagnostic tool, we hope to provide insights into the factors most likely to lead to significant improvements in bladder cancer detection and treatment standards

Standards of Detection and Evaluation
Methods
Invasive Techniques
Non-Invasive Techniques
Invasive Urine Markers
Non-Invasive Urine Markers
Cell-Based Detection
Affinity-Based
Immunocapture
Detection by Membrane Capacitance
Microfluidic
Impedance-Based Detection
DNA-Bonded Substrates
Antibody-Bonded Substrates
Future Perspectives
Findings
Concluding Remarks

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