AbstractEarly stage, disease diagnosis is of paramount importance as it maximizes chances for simpler and more effective treatment along with decreased possibility for metastasis. Decentralized diagnostic devices that promise to shrink complete biomedical laboratories in a few centimetres chips would immensely aid towards this direction and the need for such devices is ever-growing. Lab-on-Chip (LoC) with its holistic approach is a promising platform towards the implementation of Point of Care (PoC) testing which aims to bring the diagnosis at the patient’s bedside. However, advances on LoC have not been progressed to the point of vast commercialization as the mass manufacturing cost is still not at a competitive level. Lab-on-Printed Circuit Board (Lab-on-PCB) is currently considered as a promising candidate technology to transfer the LoC concept from the laboratory to the real world, demonstrating enormous potential for tackling the LoC commercial upscaling bottleneck.
Recent advances in the technology of inkjet-printers and functional materials in solution form have made viable the fabrication of fully printable electronic devices, reducing the cost significantly in comparison to the usual lithography processes. In addition, inkjet-printing appears to be the perfect match for biosensing applications as the latter do not require nm-scale capable technology.
BioFETs have been considered as one of the most promising practices for sensitive detection of disease biomarkers and research interest has been significantly increased by the recent emergence of novel, nano-materials such as graphene. The merger of BioFETs with the Lab-on-PCB concept could elevate the performance of Lab-on-PCB diagnostic microsystems far beyond their current state-of-the-art (2-3 electrodes electrochemical biosensors).
In this study, the fabrication of BioFETs by means of inkjet-printing on PCB substrates is explored with the aim to detect circulating tumor DNA (ctDNA). To begin with, inkjet-printing of silver nanoparticle and graphene inks was attempted by using a large-format, PCB-industry compatible printer. The second study focuses on the fabrication and electrical characterization of graphene BioFETs on PCBs. The PCBs were designed in CAD software and were industrially manufactured thus complying with the desired, upscalable character of the end-product. Other materials than graphene were also studied for transistor channel materials such as poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) and molybdenum disulfide (MoS2). A third study concentrates on the ctDNA sensing characterization of the developed graphene BioFETs where the selective detection of the complementary DNA sequence is shown. The sensor was fabricated by implementing suitable linker molecules for the robust immobilization of peptide nucleic acids (PNA) probes. The sensitivity to pH and ionic concentration of the buffer solution is also highlighted. This study addresses one of the major challenges of biosensors which is the output signal influence by other parameters than the analyte concentration and in this case, it is shown that the pH and ionic concentration values have to be taken into serious consideration when implementing real sample solutions as their properties cannot be controlled. Lastly, the microfluidic integration of the presented BioFETs
was also demonstrated along with the commercial manufacturing of a microfluidic device for isothermal DNA amplification with the aim to render the presented BioFETs, self-sufficient sensing devices towards the LoC approach.
In conclusion, this thesis serves as a potential orientation for overcoming the shortcomings of the current LoC field and contributes towards the development of upscalable BioFETs by implementing established commercial manufacturing technology.
|Date of Award||1 Nov 2021|
|Supervisor||Despina Moschou (Supervisor) & Pedro Estrela (Supervisor)|