The Shiddiky group is focused on the multidisciplinary research at the interface between chemistry, nanotechnology, biology and medicine. Research at this interface has the potential to generate breakthroughs in fundamental science as well as lead to advanced technologies for diagnosing, monitoring and treating disease. Current (selective) research projects are the following:
- Point-of-care (POC) diagnostics
- Microfluidic methods for the detection of cancer
- Portable devices for cancer epigenetics evaluation
- Nanomachines for exosome and exosomal biomarkers detection
- Superparamagnetic materials in biosensing applications
(1) Point-of-care (POC) diagnostics
The development of affordable, sensitive, specific, user-friendly, rapid and equipment-free diagnostic method that can detect diseases at the time and place of patient care (i.e., point-of-care) using minimal specialised infrastructure, has the potential to transform health care to millions people both in the developed and developing countries. Recent advances in sequencing and proteomics technologies have now given rise to a large number of potentially useful genetic, epigenetic and other novel molecular biomarkers for the development of diagnostic methods for many diseases including cancer, infectious and neurodegenerative diseases. Despite these great input from biomedical engineering, significant technical challenges for achieving a functional POC device are yet to be overcome. This is mainly due to the lack of sensitive, specific, rapid and low-cost readout methods. The Shiddiky group is pursuing studies of improving existing and developing entirely new methods that can rapidly detect cancer, infectious and neurodegenerative diseases. Two examples are the following:
- Early detection of cancer. Detection of cancer at the early stage of the disease – before it has had a chance to metastasize – represents one of the major challenges in the battle against cancer. Currently, a tissue biopsy followed by various molecular pathological analysis are required to formulate an accurate diagnosis of cancer subtype, staging and its impact on patient prognosis. For certain patients with varying tumour types, tissue based biopsies are often results in late stage diagnosis and poor patient survival with life threatening consequences in extreme cases. Therefore, it is appealing to search for non-invasive biomarkers to allow detection and monitoring of disease progression during or even before the course of treatment. The Shiddiky group is focused on the development of POC devices for the early stage diagnosis of cancer reliably and non-invasively.
- POC diagnostic devices for infectious diseases. Current strategies for diagnosing infectious diseases (i.e., dengue, cholera, malaria tuberculosis, etc) in impoverished regions of the world i.e., South Asia are largely inadequate. Despite recent advances in detection technologies, many patients from these regions often remain undiagnosed, in part due to the absence of affordable, sensitive and effective diagnostic tools, or diagnosed at the late stage when treatment becomes less effective. This could results in continuous and quick transmission of serious infections over the large communities, leading to major human and economic consequences for millions of people. The Shiddiky group is focused on novel molecular bioassays to generate new POC diagnostics technologies that offer early, sensitive, specific, cost effective and portable detection of infectious diseases by enabling diseases to be rapidly diagnosed ‘on the spot’ using minimal specialized infrastructure.
(2) Microfluidic methods for the detection of cancer
Often fatal cancers develop as a consequence of failed or inaccurate surveillance and there is an urgent need to develop accurate technologies for early detection of biomarkers in cancer patients. Circulating tumour cells (CTCs) disseminating through the bloodstream have been shown to correlate with survival outcomes and response to therapy. Therefore, the isolation and analysis of CTCs from patient blood samples could enable non-invasive ‘liquid biopsies’ for the early detection of cancer. However, clinical uptake of CTC measurement as a diagnostic tool has been limited by the rare abundance and difficulty of isolating CTCs from the large excess of non-target cells, proteins, and molecules present in blood samples. A major limitation of current standard CTCs analysis methods in advanced cancers (e.g. the FDA-approved Cell Search®) is the high level of ‘biological noise’ associated with low sensitivity, specificity and long analysis time. In this translational-focused research, we are focused on the development of microfluidic strategies as standard diagnostic tools for cancer patients undergoing systemic therapy and assess the impact of standard protocols in predicting response to therapy and patient outcomes.
(3) Portable devices for cancer epigenetics evaluation
Measuring epigenetic (methylation, hydroxymethylation) information in DNA is of great interest to biology and medicine. However, such information is notoriously difficult to access via conventional methodologies (e.g., bisulfite sequencing) as samples typically require cumbersome chemical treatment, amplification and readout. The Shiddiky group focuses to develop portable devices (without amplification and sample pre-processing steps) for the analysis of aberrant methylation or hydroxymethylation landscapes in unprocessed genomic DNA samples. Such a device would allow more rapid and cost effective analysis of the human methylome (and hydroxylmethylome) with diverse applications in cell biology and human health.
(4) Nanomachines for exosome and exosomal biomarkers detection
Exosomes are extracellular nano-vesicles of 30-150 nm diameter containing proteins, mRNA, and microRNAs (miRNAs) protected by a lipid bilayer. Unlike other blood-based markers such as circulating tumour cells (1-100 cells/mL of blood), exosomes are generally present in large numbers in body fluids and mediate various physiological functions such as cell to cell communication and immuno-stimulation as well as pathological processes including metastatic niche establishment in cancer. Due to their unique composition, easy accessibility and capability of representing their parental cells, exosomes (and exosome containing RNAs, proteins) draw much attention as promising biomarker for tumour screening, diagnosis and prognosis. Therefore, isolation and analysis of tumour-derived exosomes and exosome containing biomarkers could significantly improve the capacity to diagnose cancer thereby improving outcomes. The Shiddiky group is pursuing studies of the development of new nanomachineries for the highly selective isolation and sensitive detection of exosome and exosomal biomarkers (mRNA, proteins) in samples derived from cancer and neurodegenerative patients.
(5) Superparamagnetic materials in biosensing applications
Enzyme mimetic activity of ferromagnetic nanoparticle similar to that found in natural peroxidases, which are widely used to oxidise organic substrates in the biosensing systems, is well known. The Shiddiky group is focused on the development of novel sensing strategies based on highly porous magnetic nanoparticle with superparamagnetic property for molecular and cellular biomarker detection. Current interest includes POC devices for the naked-eye detection of cancer and neurodegenerative diseases.