microfluidics is the science and technology that deals with fluids usually in the range of microliters ( 10 ) to picoliters ( 10 ) .
since microfluidics typically deals with fluids in the microliter scale , it has several advantages , including low consumption of samples , short analysis time , and high sensitivity [ 1 - 4 ] .
the portability and fast processing speed of microfluidic devices also allows for in situ and real - time analysis .
polydimethylsiloxane ( pdms ) is commonly used for molding microfluidic chips because it is a transparent and biocompatible elastomer .
the fabricating process of pdms - based microfluidic devices , which is based on soft lithography , consists of the following steps : ( 1 ) master fabrication steps , including spin coating of a photoresist film , exposure , and development to form the mold on a silicon substrate ; ( 2 ) device fabrication steps , including pouring the pdms on the master , punching holes with a biopsy punch , and bonding the pdms structure to glass .
recently , paper - based microfluidic devices have been proposed as cheap , portable , and disposable devices [ 5 - 7 ] .
ever since this emerging discipline was introduced in the early 1990s , microfluidics has grown rapidly in the field of biomedical applications .
microfluidic devices are very useful tools for molecular separation , biochemical assays , drug screening , chromatography , and migration assays [ 10 - 14 ] .
lap - on - chip and organ - on - chip based on microfluidic devices have also been widely used for high - throughput screening applications .
microfluidic devices have not been widely used in urological research yet . however , some pioneering studies have been reported for bladder and prostate cancer detection , urine analysis , and sperm characterization . in this review
, we will summarize research works that use microfluidics and discuss its application in urology .
microfluidics has been considered a promising tool to analyze cancer cells and tumor function owing to its high sensitivity , high throughput , and less material consumption .
microfluidic devices offer various microenvironments for cell culture , from 2-dimensional to complex 3-dimensional systems , and the complex coculture system .
various microfluidic platforms have been developed to understand cancer cell migration and metastasis under various conditions , such as varying chemical gradients and mechanical constraints ( fig .
1 ) . a microfluidic device to detect metastatic cancer cells based on their size and deformability was also fabricated .
a microfluidic device has been developed for prostate and bladder cancer research for various procedures , including biomarker detection , characterization of cancer cells in various microenvironments , and circulating tumor detection .
prostate cancer is the most common type of cancer among males and the sixth most common cause of death in males . a prostatic - specific antigen ( psa ) , which is one of the available biomarkers of prostate cancer , is widely used for the screening of prostate cancer .
however , the conventional psa test has drawbacks , such as excessive sample consumption , restrictive control of the analytes in the reaction chamber , and lack of multiplexing capabilities .
therefore , the use of a microfluidic device has been considered an efficient approach to overcome these drawbacks .
the microfluidic enzyme - linked immunosorbent assay was integrated with photodetectors to sense the free isoform of the psa with labeled antibodies by using all 3 detection modes .
this integrated system showed enhanced reliability in signal acquisition and refined sensitivity even for low detection limits .
this platform allowed for quick screening and contemporary detection of free and total psa using 2 different antibodies that are immobilized on a single chip .
bladder cancer is a common urologic cancer that has the highest recurrence rate among all other malignancies .
the microfluidic - based microenvironment is a good model to investigate the tumor growth , metastasis , and dynamic interplay between the cells .
the mitochondrial - related protein expression in the bladder cancer cells was investigated in coculture conditions using a microfluidic chip .
a chip for the coculture of bladder tumor cells and fibroblasts was composed of 2 cell culture pools for human skin fibroblasts and the human bladder tumor cells .
the pools were connected using microchannels and peripheral perfusion channels . using this coculture system ,
it was observed that the high - energy metabolites transferred to adjacent tumor cells in a specified direction . to study the effects of the microenvironment on bladder cancer , the microfluidic device based on 4 types of cells coculture system was suggested .
this system consisted of perfusion equipment , matrigel channel units , a medium channel , and four indirect contact culture chambers in which the 4 types of cells ( stromal cells , fibroblasts , endothelial cells , and macrophages ) could be cultured simultaneously .
the changes in urine composition , such as the changes in the levels of glucose , albumin , creatinine , and uric acid , may provide information about organ dysfunctions , drug abuse , and exposure to chemicals and toxins .
conventional methods to examine urine samples are physical ( color , odor , etc . ) , biochemical , and microscopic examinations .
microfluidic devices are typically used in the manipulation of fluids with a small quantity of sample , under a precisely controlled flow rate .
therefore , they are very useful devices for urine sample pretreatments and sensing urinary molecules .
liquid extraction as a sample pretreatment device prior to carrying out gas chromatography analysis of the amphetamine - type stimulants in the urine ( fig .
the interface between the organic solvent and alkalized urine was stabilized by using the microchannels modified by a capillary - restricted modification method .
microfluidic devices have been used for the detection of urinary macromolecules , including protein , virus , and bacteria .
demonstrated the cost - effective detection of the bk virus ( viral load ) from nonpretreated urine samples using microfluidic devices .
a detection sensitivity of as low as 12 viral copies was obtained by the integration of a small volume genetic amplification ( polymerase chain reaction ) .
microfluidic devices for urinary micromolecules , including creatinine , galactose , and inorganic ions have also been demonstrated by several groups . for analyzing urinary creatinine , a microfluidic system based on a 2-point alkaline picrate kinetic reaction
the microchip was connected to 2 syringes for delivering the samples , and it was connected to a miniature fiber optic spectrophotometer for measuring the absorption light at 510 nm .
the integration of microfluidic devices with different approaches , including electrophoresis , optics , and immunoassays , was successfully used for detecting drugs and metabolites in urine samples .
caffeine and theophylline could be effectively separated using the microchannel electrophoresis integrated with electrochemical detection , and illicit drugs were detected with a high accuracy using the microfluidic device with an ultraviolet detection function .
many microfluidic systems have been proposed for quantifying sperm quality and sorting sperm by their motility . according to the principle , the microfluidic device for sperm sorting
can be categorized into the following 3 groups : passively driven devices , flow - driven devices , and combined devices for thermotaxis and chemotaxis .
the principle of passively driven devices is that motile sperm can be collected within a specific period of time in the outlet of the microfluidic channels , while less - motile sperm are left behind in the microchannels . in flow - driven devices
the sperm are segregated into different channels depending on their motility and are counted thereafter . the combined microfluidic device with a chemoattractant was fabricated with a straight channel connected to a bi - branch channel .
the sperm motility under the chemical gradient was monitored , and the chemotaxis was analyzed by using the ratio of the sperm collected in different branches .
microfluidics has been considered a promising tool to analyze cancer cells and tumor function owing to its high sensitivity , high throughput , and less material consumption .
microfluidic devices offer various microenvironments for cell culture , from 2-dimensional to complex 3-dimensional systems , and the complex coculture system .
various microfluidic platforms have been developed to understand cancer cell migration and metastasis under various conditions , such as varying chemical gradients and mechanical constraints ( fig .
1 ) . a microfluidic device to detect metastatic cancer cells based on their size and deformability was also fabricated .
a microfluidic device has been developed for prostate and bladder cancer research for various procedures , including biomarker detection , characterization of cancer cells in various microenvironments , and circulating tumor detection .
prostate cancer is the most common type of cancer among males and the sixth most common cause of death in males . a prostatic - specific antigen ( psa ) , which is one of the available biomarkers of prostate cancer , is widely used for the screening of prostate cancer .
however , the conventional psa test has drawbacks , such as excessive sample consumption , restrictive control of the analytes in the reaction chamber , and lack of multiplexing capabilities .
therefore , the use of a microfluidic device has been considered an efficient approach to overcome these drawbacks .
the microfluidic enzyme - linked immunosorbent assay was integrated with photodetectors to sense the free isoform of the psa with labeled antibodies by using all 3 detection modes .
this integrated system showed enhanced reliability in signal acquisition and refined sensitivity even for low detection limits .
this platform allowed for quick screening and contemporary detection of free and total psa using 2 different antibodies that are immobilized on a single chip .
bladder cancer is a common urologic cancer that has the highest recurrence rate among all other malignancies .
the microfluidic - based microenvironment is a good model to investigate the tumor growth , metastasis , and dynamic interplay between the cells .
the mitochondrial - related protein expression in the bladder cancer cells was investigated in coculture conditions using a microfluidic chip .
a chip for the coculture of bladder tumor cells and fibroblasts was composed of 2 cell culture pools for human skin fibroblasts and the human bladder tumor cells .
the pools were connected using microchannels and peripheral perfusion channels . using this coculture system ,
it was observed that the high - energy metabolites transferred to adjacent tumor cells in a specified direction . to study the effects of the microenvironment on bladder cancer , the microfluidic device based on 4 types of cells coculture system was suggested .
this system consisted of perfusion equipment , matrigel channel units , a medium channel , and four indirect contact culture chambers in which the 4 types of cells ( stromal cells , fibroblasts , endothelial cells , and macrophages ) could be cultured simultaneously .
the changes in urine composition , such as the changes in the levels of glucose , albumin , creatinine , and uric acid , may provide information about organ dysfunctions , drug abuse , and exposure to chemicals and toxins .
conventional methods to examine urine samples are physical ( color , odor , etc . ) , biochemical , and microscopic examinations .
microfluidic devices are typically used in the manipulation of fluids with a small quantity of sample , under a precisely controlled flow rate .
therefore , they are very useful devices for urine sample pretreatments and sensing urinary molecules .
liquid extraction as a sample pretreatment device prior to carrying out gas chromatography analysis of the amphetamine - type stimulants in the urine ( fig .
the interface between the organic solvent and alkalized urine was stabilized by using the microchannels modified by a capillary - restricted modification method .
microfluidic devices have been used for the detection of urinary macromolecules , including protein , virus , and bacteria .
demonstrated the cost - effective detection of the bk virus ( viral load ) from nonpretreated urine samples using microfluidic devices . a detection sensitivity of as low as 12 viral copies was obtained by the integration of a small volume genetic amplification ( polymerase chain reaction ) .
microfluidic devices for urinary micromolecules , including creatinine , galactose , and inorganic ions have also been demonstrated by several groups . for analyzing urinary creatinine , a microfluidic system based on a 2-point alkaline picrate kinetic reaction
the microchip was connected to 2 syringes for delivering the samples , and it was connected to a miniature fiber optic spectrophotometer for measuring the absorption light at 510 nm .
the integration of microfluidic devices with different approaches , including electrophoresis , optics , and immunoassays , was successfully used for detecting drugs and metabolites in urine samples .
caffeine and theophylline could be effectively separated using the microchannel electrophoresis integrated with electrochemical detection , and illicit drugs were detected with a high accuracy using the microfluidic device with an ultraviolet detection function .
many microfluidic systems have been proposed for quantifying sperm quality and sorting sperm by their motility . according to the principle ,
the microfluidic device for sperm sorting can be categorized into the following 3 groups : passively driven devices , flow - driven devices , and combined devices for thermotaxis and chemotaxis .
the principle of passively driven devices is that motile sperm can be collected within a specific period of time in the outlet of the microfluidic channels , while less - motile sperm are left behind in the microchannels . in flow - driven devices
the sperm are segregated into different channels depending on their motility and are counted thereafter . the combined microfluidic device with a chemoattractant was fabricated with a straight channel connected to a bi - branch channel .
the sperm motility under the chemical gradient was monitored , and the chemotaxis was analyzed by using the ratio of the sperm collected in different branches .
although a microfluidic system has many advantages , it is still a relatively new technology in the field of urology research .
recently , some successful implementations of microfluidic devices have been demonstrated for cancer diagnosis , urine analysis , and sperm sorting .
however , more promising microfluidic systems and research works are required for such systems to be applied in the clinic .
therefore , it is important to continue the development of this new technology in cooperation with the relevant users .
 microfluidics is considered an important technology that is suitable for numerous biomedical applications , including cancer diagnosis , metastasis , drug delivery , and tissue engineering . 
 although microfluidics is still considered to be a new approach in urological research , several pioneering studies have been reported in recent years . in this paper , we reviewed urological research works using microfluidic devices . 
 microfluidic devices were used for the detection of prostate and bladder cancer and the characterization of cancer microenvironments . 
 the potential applications of microfluidics in urinary analysis and sperm sorting were demonstrated . 
 the use of microfluidic devices in urology research can provide high - throughput , high - precision , and low - cost analyzing platforms . 