Heater Integrated Lab-on-a-Chip Device for Rapid HLA Alleles Amplification towards Prevention of Drug Hypersensitivity

Abstract

HLA-B*15:02 screening before administering carbamazepine is recommended to prevent life-threatening hypersensitivity. However, the unavailability of a point-of-care device impedes this screening process. Our research group previously developed a two-step HLA-B*15:02 detection technique utilizing loop-mediated isothermal amplification (LAMP) on the tube, which requires two-stage device development to translate into a portable platform. Here, we report a heater-integrated lab-on-a-chip device for the LAMP amplification, which can rapidly detect HLA-B alleles colorimetrically. A gold-patterned micro-sized heater was integrated into a 3D-printed chip, allowing microfluidic pumping, valving, and incubation. The performance of the chip was tested with color dye. Then LAMP assay was conducted with human genomic DNA samples of known HLA-B genotypes in the LAMP-chip parallel with the tube assay. The LAMP-on-chip results showed a complete match with the LAMP-on-tube assay, demonstrating the detection system’s concurrence.

Recent advances and challenges in temperature monitoring and control in microfluidic devices

“…This configuration enabled an electrothermal fluidic roll that went from 21 to 29°C, which can be used in LOC applications. Common rectangle heaters have also been used to work with biological samples as human DNA, animal cells, and protein cells because of their appreciable accuracy of 0.1°C in the range of 25–65°C [ 142 , 157 ]. Finally, another variation involves the use of a heater chuck with three heating cartridges, as established by de Haas et al., that permits the characterization of microfluidic properties of materials in high temperatures, ranging from 130 to 190°C [ 158 ].…”

High-Performance, Easy-to-Fabricate, Nanocomposite Heater for Life Sciences and Biomedical Applications

“…Whether to control temperature-dependent processes [ 1 , 2 , 3 , 4 , 5 ], drive actuators [ 6 , 7 , 8 ], or as part of sensing mechanisms [ 4 , 9 , 10 , 11 , 12 ], microheaters have found applications in the chemical, food processing, automotive, aeronautic, and biomedical and pharmaceutic industries, to cite a few (see, e.g., ref. [ 11 , 13 , 14 , 15 , 16 , 17 , 18 ]).…”

“…Another advantage of operating at the microscale is the increased surface-to-volume ratio that favors thermal transfer. We borrow examples from microfluidics where this feature is used to quickly heat up solutions, for example, in DNA amplification (e.g., polymerase chain reaction [ 20 , 21 ] or loop-mediated isothermal amplification [ 1 , 17 ]) or for cell culture in bioreactors [ 22 , 23 ] and also in electrophoretic separation where large electric fields can be applied without excessive heating due to improved thermal dissipation under flow [ 24 , 25 ]. The above observations highlight the excellent performances of Joule-based microheating, which enables fast, precise, and accurate control of temperatures with low power consumption, as confirmed in other studies [ 16 , 26 ].…”

Electric cell-substrate impedance sensing in biocompatibility research

“…However, the possibility of using specific materials requires testing their biocompatibility, i.e. their effect on living organisms [ 1 , 2 , 3 ].…”