An Ultrasonic System-on-a-chip for Early Cancer Diagnosis
Lead Research Organisation:
Cardiff University
Department Name: Sch of Engineering
Abstract
A cancer becomes life-threatening when the primary tumour spreads from the place where it first started to another place in the body. The spreading process is called metastasis, a tumor formed by spreading cancer cells is called a metastatic tumor. Metastasis is the principal cause of death in patients diagnosed with invasive cancer. The metastatic mechanism has been intensively researched but not fully understood. It has been reported that tumour cells shed by the primary tumour to blood stream, namely circulating tumour cells (CTCs), are the seeds for cancer metastasis.
Research on CTCs such as their population, isolation from the blood, genotyping, and phenotyping holds the key to understanding the biology of metastasis. CTCs are extremely rare, even in patients with metastatic cancer (approximately one count among a billion normal blood cells), and their isolation is greatly subject to technological constraints. This project will develop an ultrasonic system-on-a-chip (USC) for separating CTCs from blood samples based on CTCs' mechanical properties such as size, density, and compressibility.
Parametric numerical simulations of the USC will be investigated to design optimum device geometry, sensitivity, and throughput in order to advance the current application of acoustic-based sensor in microparticle separation. The USC should be able to manipulate extremely low concentration of CTCs as they are found only several in 1-mL blood sample but sufficient for seeding secondary tumour in a cancer patient. The expected recovery rate of CTCs is more than 90% in order to realise the implementation of the USC in clinical applications. Microsystem fabrication with ultrasound techniques will be involved in this project to develop the Ultrasonic System on a Chip. Preliminary studies of clinical samples will take place to offer the potential to serve as invaluable supplemental tool in cancer research, especially in early cancer diagnosis and drug efficacy assessment.
Research on CTCs such as their population, isolation from the blood, genotyping, and phenotyping holds the key to understanding the biology of metastasis. CTCs are extremely rare, even in patients with metastatic cancer (approximately one count among a billion normal blood cells), and their isolation is greatly subject to technological constraints. This project will develop an ultrasonic system-on-a-chip (USC) for separating CTCs from blood samples based on CTCs' mechanical properties such as size, density, and compressibility.
Parametric numerical simulations of the USC will be investigated to design optimum device geometry, sensitivity, and throughput in order to advance the current application of acoustic-based sensor in microparticle separation. The USC should be able to manipulate extremely low concentration of CTCs as they are found only several in 1-mL blood sample but sufficient for seeding secondary tumour in a cancer patient. The expected recovery rate of CTCs is more than 90% in order to realise the implementation of the USC in clinical applications. Microsystem fabrication with ultrasound techniques will be involved in this project to develop the Ultrasonic System on a Chip. Preliminary studies of clinical samples will take place to offer the potential to serve as invaluable supplemental tool in cancer research, especially in early cancer diagnosis and drug efficacy assessment.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509449/1 | 01/10/2016 | 30/09/2021 | |||
| 1943656 | Studentship | EP/N509449/1 | 01/10/2017 | 18/03/2022 | Thomas McCloy |
| Description | The Belousov-Zhabotinsky reaction has been widely used a chemical system to model biological oscillations, like the beating of the heart or transmission of neuronal signals. Examples in the literature show the generation of droplet networks of the Belousov-Zhabotinsky reaction separated by lipid membranes, and droplet to droplet communication has been facilitated through passive diffusion of molecules. My work has expanded upon this by incorporating pore-forming proteins and peptides into the membranes. It is a key advancement as it permits new means of droplet-droplet communication through ionic flow. Additionally, the pore-forming peptide used is voltage sensitive meaning that the network is able to respond to an external stimuli. The effect of this integration is making this model more bioligical-like. Arrays of Belousov-Zhabotinsky droplet are typically generated via quite traditional microfluidics, like milling or PDMS soft lithography. Initial work has used 3D printing to produce microfluidic devices, and it permits highly versatile geometry. By changing the geometry, it opens up the possibility of creating a greater degree of communication and order. |
| Exploitation Route | Unconventional communication often uses the Belousov-Zhabotinsky reaction as a means of performing logical operations, for instance a NAND gate. By being able to open/shut channels between droplet networks, it adds a higher level of control over the soft computer. I envisage academics taking this finding forward and using proteins/peptides to perform more logical operations with the Belousov-Zhabotinsky reaction. The Belousov-Zhabotinsky reaction attracts much interest due to its striking color change and ability to self-form mesmerizing patterns. Using 3D printing to generate emulsions of this chemical reaction will likely attract much interest in the use of 3D printing for microfluidics and encourage more development in 3D printing by academics and by industry. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | Combination of LAMP-BART with Microfluidics and Encapsulated Droplet Interface Bilayers (eDIBs) |
| Organisation | Cardiff University |
| Department | School of Biosciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I used microfluidics and control software to generate a gradient of DNA template for the LAMP-BART reaction (Light amplification bio-luminescent assay in real time) and subsequently imaged it with a bio-luminescent imager. This showed the relationship between the amount of DNA template and the time for the peak light emission. This work is being used in a publication in progress, and I have produced 2 figures for said paper. |
| Collaborator Contribution | Our biosciences partner is the expert on the LAMP-BART reaction and was responsible for production. My colleague in the Wales School of Pharmacy and Pharmaceutical Sciences encapsulated the assay in a robust alginate shell using a published technique. All partners contributed by paper drafting and figure publication too |
| Impact | Paper: Bioluminescent Detection of Isothermal DNA Amplification in Microfluidic Generated Droplets and Artificial Cells. This has been sent to the journal Small and is under-review. |
| Start Year | 2019 |
| Description | Brilliant Club - Delivered Tutorial Series |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Along with the charity Brilliant Club, I delivered two tutorial series to two secondary schools in the South Wales area. These focused on introducing students to the idea of secondary-style education and raising aspirations for the future of young people from deprived backgrounds. |
| Year(s) Of Engagement Activity | 2018 |