Programme

10:00 – 10: 45 

Dr Aleksandar Ivanov, Department of Chemistry Imperial College

alex.ivanov@imperial.ac.uk

Nanoscale Strategies for Single-Molecule and Single Cell Analysis

There has been a significant drive to deliver nanotechnology-based solutions that allow analysis of the fundamental building blocks of life, both at the scale of single molecules and of individual cells. In this talk, I will present nanoscale sensors and platforms that we have recently developed towards addressing central challenges both for single molecule and single cell analysis.

 The first part of my talk will discuss nanopore-based single molecule strategies that enable high sensitivity and selectivity for trace analyte detection in biological fluids and have implications on next-generation biomarker analysis in the laboratory and clinical setting. Examples include introducing analyte selectivity in solid-state nanopores by via functionalization with embedded receptors in ionic field effect transistors^1,2 and using aptamer-functionalised molecular carriers strategies^3,4. I will also report on some of our recent strategies to control molecular transport using individually addressable double nanopores⁵, zeptoliter sized single molecule traps⁶ and tunable hydrogel-filled nanopores⁷.

 In the second part of the talk, I will report on a new type of nanotweezers capable of trapping and extracting single entities such as DNA, RNA and mitochondria from a living biological cell could help better understand the fundamentals of cellular processes and how these processes occur in real time.⁸ The nanotweezers, which does not damage cells, unlike many existing such analytical techniques, could also help in the construction of the Human Cell Atlas – the most ambitious genomics project after the sequencing of the human genome. This work bridges the gap between single-molecule/organelle manipulation and cell biology and can ultimately enable a better understanding of living cells.

1. Ren et al., Nature Communications 2017, 8, 586
2. Xue et al, ACS Applied Materials & Interfaces 2018, 10 (44), 38621-38629
3. Sze et al., Nature Communications 2017, 8, 1552
4. Cai et al., Nature Communications 2019
5. Cadinu,  Campolo et al., Nano Letters 2018, 18 (4), 2738–2745
6. Cadinu et al., Nano Letters 2017, 17 (10), 6376-6384
7. Al Sulaiman et al., Nano Letters 2018, 18 (9), 6084-6093 2018
8. Nadappuram Cadinu et al Nature Nanotechnology 2019 14, 80–88 

Dr Alex Ivanov is IC Research Fellow at the Department of Chemistry, Imperial College London. His research focuses on the innovation of novel nanoscale sensors and platforms for single-molecule detection and delivery, that enable the studying of fundamentally important molecules in chemistry, biology, and medicine. Key examples include tunnelling nanopore platforms for high-resolution DNA fragment sizing and sequencing applications Nano Lett. (2011), ACS Nano (2014), on-demand delivery of single molecules, ACS Nano (2015), label-free single molecule detection in ultra-dilute (fM) samples, Nat. Commun. (2016), multi-channelled probes for confinement and ultrasensitive for detection of small proteins, Nano Lett. (2017, 2018), selective recognition of single proteins in complex samples, Chem Sci (2017), Nat. Commun.  (2017A), Nat. Commun.  (2019),  nanoscale transistor based single-molecule probes, Nat. Commun. (2017B), ACS A.M.I. (2018), single molecule nanotweezers that can extract single DNA, proteins and organelles from living cells, Nature Nanotechnology (2019) to name a few.

10:45 – 11:00 Coffee/tea break

11:00 – 12:00

Professor Jonathan Cooper

Origami DNA Diagnostics – Species Specific Multiplexed Detection of Infectious Diseases in Underserved Rural Communities

We have devised an origami-inspired paper device as a low-cost, rapid, and easy-to-use field test to help combat the spread of infectious diseases, like malaria. Although healthcare workers utilize various accepted methods, many of these standard tests have proven unreliable and impracticable, especially in remote, rural communities that lack refrigeration and laboratory equipment. To address the growing need for better tests, we have developed a paper, origami-inspired field device that provides fast, high-quality, species-specific malaria diagnostics that compare favorably to PCR laboratory assays, the current gold standard. Requiring just a wax printer and hot plate, the design draws on origami folding techniques to create a paper device which prepares blood samples for a field-friendly amplification technique known as loop-mediated isothermal amplification, or LAMP. The device is further augmented with microfluidic lateral flow LAMP amplification and a simple multiplexed detection platform that can diagnose different malaria species from a finger-prick blood sample.

As a demonstration, we present a double-blind, first-in-human trial with rural primary schools in Mayuge and Apac Districts in Uganda that show the device outperforms other established techniques, detecting malaria in 98% of infected participants.  We have also shown that the techniques can be used in a variety of other environmental and veterinary applications, with sampling from faeces, sperm and water in studies in India and China. Our overall vision is to work with healthcare technologists and social scientists to explore baseline diseases epidemiologies, mechanisms of zoonotic disease transmission, multi-morbidities caused by co-endemic diseases as well as the interaction between infectious and non-communicable diseases. We are also currently developing a social enterprise, working with the Ministry of Health, Uganda and the Ugandan Industrial Research Institute for the local manufacture of these devices.

Professor Jon Cooper holds The Wolfson Chair in Biomedical Engineering. He is an EPSRC Research Fellow and has a European Research Council Advanced Programme Grant. His major research interests are in ultrasonics, microfluidics and medical diagnostics. He has a track record of spin-out and translation of devices into industry and clinical practice. He has been elected as a Fellow of the Royal Academy of Engineering (UK’s national academy of engineering) as well as a Fellow of the Royal Society of Edinburgh (Scotland’s National Academy of arts, humanities and sciences).