title: A negative-pressure-driven microfluidic chip for the rapid detection of a bladder cancer biomarker in urine using bead-based enzyme-linked immunosorbent assay.
abstract: This paper describes an integrated microfluidic chip that is capable of rapidly and quantitatively measuring the concentration of a bladder cancer biomarker, apolipoprotein A1, in urine samples. All of the microfluidic components, including the fluid transport system, the micro-valve, and the micro-mixer, were driven by negative pressure, which simplifies the use of the chip and facilitates commercialization. Magnetic beads were used as a solid support for the primary antibody, which captured apolipoprotein A1 in patients' urine. Because of the three-dimensional structure of the magnetic beads, the concentration range of the target that could be detected was as high as 2000 ng ml(-1). Because this concentration is 100 times higher than that quantifiable using a 96-well plate with the same enzyme-linked immunosorbent assay (ELISA) kit, the dilution of the patient's urine can be avoided or greatly reduced. The limit of detection was determined to be approximately 10 ng ml(-1), which is lower than the cutoff value for diagnosing bladder cancer (11.16 ng ml(-1)). When the values measured using the microfluidic chip were compared with those measured using conventional ELISA using a 96-well plate for five patients, the deviations were 0.9%, 6.8%, 9.4%, 1.8%, and 5.8%. The entire measurement time is 6-fold faster than that of conventional ELISA. This microfluidic device shows significant potential for point-of-care applications.
authors.affiliation: Department of Electronic Engineering, Chang Gung University, Taoyuan 333, Taiwan ; Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan ; Graduate Institute of Medical Mechatronics, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Yen-Heng
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Electronic Engineering, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Electronic Engineering, Chang Gung University, Taoyuan 333, Taiwan ; Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Chao-Sung
authors.initials: CS
authors.lastname: Lai
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Chang Gung Bioinformatics Center, Department of Urology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
authors.forename: Chien-Lun
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang