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Engineering an isothermal amplification strategy for ultrasensivite and quantitative detection of microRNA cancer biomarkers

Project

Project Details

Program
BioEngineering
Field of Study
Bioengineering and Material Science
Division
Physical Sciences and Engineering

Project Description

MicroRNA (miRNA) are short (~22 nt) non-coding RNA that have emerged as highly promising diagnostic and prognostic biomarkers due to their gene regulatory functions and dysregulated expression profiles in many diseases including cancer. While promising, their absolute quantification is challenging due to their short lengths, low circulating concentrations, and high sequence homology among family members. The gold standard method for miRNA detection, based on reverse-transcription qPCR, involves complex multistep procedures and requires thermal cycling, trained personnel and bulky equipment. This project aims to develop a novel quantitative and isothermal strategy for ultrasensitive detection of miRNA at the point-of-care, i.e. in a simple, cost-effective and efficient manner from minute volumes of a patient's biological fluid sample. This project will include advancements in biomolecular engineering, biomaterials development, and biochemistry. Ultimately, this project will lead to the development of highly sensitive point-of-care biosensors for cancer diagnosis, prognosis or monitoring based on multiplex detection of microRNA cancer biomarkers from a minimally-invasive 'liquid biopsy' test.

About the Researcher

Dana Alsulaiman
Assistant Professor, Material Science and Engineering
Physical Science and Engineering Division

Affiliations

Education Profile

  • Postdoctoral Associate, Massachusetts Institute of Technology, USA, 2021
  • Postdoctoral Fellow, Massachusetts Institute of Technology, USA, 2020
  • Ph.D. Bioengineering, Imperial College London, UK, 2019
  • B.Eng. and M.Eng. Biomedical Engineering, Imperial College London, UK, 2015

Research Interests

a€‹Dr Al-Sulaiman's research focuses on the development of next generation biosensing platforms to detect an emerging class of disease biomarkers called cell-free nucleic acids including microRNA and cell-free DNA. At the intersection between polymeric biomaterials and microtechnologies, her research includes advancements in hydrogel beads, microparticles, microneedles and microarrays. She is also interested in single-molecule detection technologies, namely nanopore sensors, for the detection and characterization of rare disease biomarkers. Dr Al-Sulaiman's research aims to tackle urgent clinical needs including early detection and monitoring of cancer and Alzheimer's disease in addition to understanding the skin microbiome.

Selected Publications

  • Al Sulaiman, Dana, Alfie Gatehouse, Aleksandar P. Ivanov, Joshua B. Edel, and Sylvain Ladame. ""Length-Dependent, Single-Molecule Analysis of Short Double-Stranded DNA Fragments through Hydrogel-Filled Nanopores: A Potential Tool for Size Profiling Cell-Free DNA."" ACS Applied Materials & Interfaces (2021).
  • Al Sulaiman, Dana, Sarah J. Shapiro, Jose Gomez-Marquez, and Patrick S. Doyle. ""High-Resolution Patterning of Hydrogel Sensing Motifs within Fibrous Substrates for Sensitive and Multiplexed Detection of Biomarkers."" ACS Sensors (2020).
  • Al Sulaiman, Dana, Jason YH Chang, Nitasha R. Bennett, Helena Topouzi, Claire A. Higgins, Darrell J. Irvine, and Sylvain Ladame. ""Hydrogel-coated microneedle arrays for minimally invasive sampling and sensing of specific circulating nucleic acids from skin interstitial fluid."" ACS Nano 13, no. 8 (2019): 9620-9628.
  • Al Sulaiman, Dana, Paolo Cadinu, Aleksandar P. Ivanov, Joshua B. Edel, and Sylvain Ladame. ""Chemically modified hydrogel-filled nanopores: a tunable platform for single-molecule sensing."" Nano Letters 18, no. 9 (2018): 6084-6093.
  • Al Sulaiman, Dana, Jason YH Chang, and Sylvain Ladame. ""Subnanomolar detection of oligonucleotides through templated fluorogenic reaction in hydrogels: controlling diffusion to improve sensitivity."" Angewandte Chemie International Edition 56, no. 19 (2017): 5247-5251.

Desired Project Deliverables

The aim of the project will be to deliver the following main objectives: - Develop an isothermal amplification methodology and strategy for miRNA detection - Characterize the analytical performance of the developed assay (sensitivity, specificity, dynamic range, etc) - Optimize the analytical performance and validate the assay with synthetic and clinical samples - Submit a report on the preliminary results which will be used as a platform for a peer-reviewed research article

Recommended Student Background

Biomolecular Engineering
Biomaterials
Biology
Biochemistry