Engineering platform technologies for public screening of Prostate Cancer

Engineering platform technologies for public screening of Prostate Cancer

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Starting. With likely kind of sad in depressing, statistics which. Is basically that one in, eight men will, actually get prostate, cancer, so at my level but not very. Much we can do to actually kind of make this statistic, change what, we can try and do is make sure but these, kind of prostate cancer are diagnosed, at an, early enough stage so, that treatment, can actually be found and actually, kind of patient, survive, and kind, of have, a kind of a very kind of healthy rest of their life so. Currently, prostate. Cancer and this is actually kind of true for many other cancer. Types in the UK is, diagnosed. Too late so, every single year you will have around 35,000. New cases only. In the UK and around, a quarter of them would, be already metastatic. That, means that we already started, spreaded, spreading, to, other organs, which, means that we actually kind of treatment. Will be much more complicated and the survival, rate much, lower, the. Only way to try to actually kind of diagnosed, with cancer earlier. Is to try to have some kind of non-invasive. Non-invasive. Diagnostic. Or. Screening test so that people can actually go and get tested on the, kind, of regular, basis even, in the absence of any clinical, symptoms, when, you often have clinical symptoms it can be too late and that means we're, confirming already have started spreading so, there is currently, a blood test for, prostate cancer which. I get everybody, in this room has heard, of and, basically. When. A man will have some, first clinical, symptoms, that could range from urine. Hesitancy. Erectile, dysfunction, or decreased, urination flow we'll, go and see their GP. Which. Will try to do an initial diagnosis. To, options in here the first one is a blood test I was referring to which. Is basically a blood test looking, at a biomarker, which is called prostate, specific antigen or. PSA. Your. Sample will be sent to an analysis Center we are going to try to see how much of its biomarker, you have in blood if it's above a certain threshold then. The GP will basically have a doubt and say well potentially, this is an indication that you have prostate cancer it's, not enough in itself to tell you for sure that you have prostate cancer and the main issue with this test is that if. You have a level of PSA, above, the threshold which is currently recommended, by the NHS, you still have about 75%, chances. But, you don't actually have prostate. Cancer but. Because you have a risk the GP has to basically try to make sure whether. You have or you haven't prostate, cancer and will, potentially. Recommend, a more invasive kind. Of. Diagnostics. Which, can, go from digital. Rectal examination or, even more invasive kind. Of a rectal kind of a biopsy to, try to take a tissue of your prostate and see, whether you, actually have or not prostate, cancer both, of em being obviously highly unpleasant and can, actually lead to some complication. And even, in some cases trigger. Some. Kind of infection of the, prostate, so. For, this reason because, the blood test it does is not specific, enough and lead to, many false positive, if, you look at the NHS website, they basically say we can't actually kind of sponsor a screening program purely. Based on this blood test instead. We're, telling you this, is where the blood test does with.

Other Pros and cons, of this test up, to you to decide whether you actually want to go for it and actually, kind of take this as a, initial. Diagnostics. Or not. So. This is where, engineers. Will try to kind of come in play and try to cannot make this change, so what we try to do is increase survival, rate of patients, with, prostate cancer by. Treating them early. Only, if necessary and, then trying, to choose the best suited, drug, for, the treatment. So. To be able to do that where, you need to have some highly specific biomarkers. Or combination. Of biomarkers, as I mentioned in previous slides PSA. Is one biomarker, specific. For prostate but, has too many false negative, a false positive that, means that you can't really trust the result out of it so we need a biomarker. Which, if we can detect it in whatever sample. You look at you, can be sure of. Receive, an indication of prostate. Cancer or, not. But. You also need some non-invasive tests for widespread public, screening so, you can have the best biomarker, possible, which, will detect cancer, as, soon. As it actually starts, appearing, in prostate if, a patient doesn't go to the GP and get tested then. That. Will not have any impact, and we not actually lead to kind of earlier diagnosis. This, is why I believe. Personally, but the best way to actually kind of detect. These cancers, early is to have some low-cost non-invasive, tests that, are compatible with widespread public, screening, and for, this we need to be affordable, robust, I needed to use which, is very clear challenge we've set ourselves, I must. Say that this, is where the collaborative, aspect of our research comes, in I think, I'm a chemist, or an engineer, that means that my expertise, in this area I'm. Not qualified enough sorry. I'm not qualified enough to actually. Detect. And validate, cancer. Biomarkers, this, is why all of my work will I on collaboration. With, cancer, biologists or clinician we, can actually kind of come up do. Some kind of clinical trials, and try to find these biomarkers. Very. Kind of modestly all of the work we're doing in here is try to find technologies, that can detect biomarkers, which, have been identified, and validated by. Clinician. Or cancer biologists.

So. Our approach our approach, is the following trying, to develop a very, simple, blood test so, I guess PSA, test involves. Some kind of drawing of blood and of a slightly more invasive way what we try to do is a more kind of a point-of-care test, but, we'd only require, a small kind of pricking of your finger generate. A few drops of blood that, will be loaded directly, onto a small portable canister, single-use. Device, this. Looks very kind, of similar, to a pregnancy test this is a very poor analogy but I will refer back to this quite a lot this, is basically something similar we're trying to do in here is something that goes from, biofeed, of a patient, onto a, device no. Other external manipulation. From, any practice, GPS, or anything it, all happens in this not. To black box but in a white box in this case and then, you have a readout, we, tells you yes or no this, is obvious is not, and. We, idea being that this test is then put into a small low-cost machine which is going to be present in your GPS clinic you can actually can insert into it and get the results, or the outcome, of your test so, for this we need mini ball oops. We, need minimal sample, volumes. We don't really want to kind of draw milliliters. Of blood from the patient it's, not really idea of a public screening we want an automated sample, processing, benchtop. Analysis. And obviously, compared, to PSA very, high specificity, and, the low cost if you want this kind of test to be sponsored by your organization like, the NHS. So. Be. Scared I'm going to show a few slides which may look kind of quite kind of scientific, or complex at the first instance but just want to kind of set the scene a little bit so, the target we're looking at our, cold circulating. Micro. Rna's so. You've, all heard. At. Least in the news cannot, the genetic test and DNA and RNA a very good biomarkers, most, of this test often refer, to DNA, which are present in all of your cells and lead to the kind of production. Of protein and so on both, are not the kind of type of DNA RNA we are interested, in both. Present, in cells are much kind of less, easily accessible, so we try to kind of find biomarkers, which, can be accessible in a much more non-invasive, way so, the good thing we both biomarkers. Is there actually offer, the majority, of DNA and RNA in cells a small proportion of em is actually, by, a complex, mechanisms, ending, up into. Your, bloodstream so that means because, we are in the bloodstream we are much more easily easily accessible. And both present, within, the, tissue and cells. So. That's the kind of a good side of a, story we are in body fluids they are in urine they are in saliva we are in blood which, means they are ideal for minimally. Invasive, diagnosis, the, downside, of this is that, in these fluids, compared, to cells their, concentration. Is much lower but, means that when you want to detect them you need technology, which is much more sensitive and, all. Of these different, pieces. Of RNA, which, we are trying to detect some, a specific, of prostate, cancer well. We all have very similar, sequences. So we're basically all very similar. To each other that, means that if you want to only detect the one which are indicative of prostate, cancer you need to have a technology which is also highly specific so. You need something which. Is reliable, sensitive. Specific. And quantitative, to get a good diagnostics. So. There are technologies, out there which allow you to detect this kind of molecular biomarkers, but. We have a number of issues which.

Affect The. Sensitivity. Specificity and. Suitability. For public, screening. Sensitivity. Is the first one as I said with, only few of these biomarkers, which are floating in your blood that. Means that the technology, which, are currently available, require. Ways, of kind of amplifying, these molecules, we, don't have, technology is good enough to detect only these few molecules we, try to find ways to cannot, multiply them to facilitate the. Detection principle. All revealed amplification. Induced. Contamination. And sources, of error, specificity. Loss or problem the molecule you use to detect these biomarkers, of an lack specificity and, all. Of the equipment, and consumables, you need to detect these biomarkers, are so highly expensive so. All of this means that the technology, which already out there are, basically, not suitable, for point-of-care, testing. Based. Forward, detection of these biomarkers, again. Very, quickly I will go through about you to show you how we, actually try to approach this system, this is the technology we've been developing in my lab which, is basically assuming, that this is the molecule, you want to detect as chemists. We know how to design, molecule, that can actually bind to this biomarker, of interest, in. Our case we, designed two different molecules that we bind to different parts of the. Biomarker, of interest, the, first one will bind on the left hand side the, second one on the right hand side and when these two molecule, which we've designed bind to the only microwave interest. Chemical. Reaction take place and let's, assume invest case you have a change of the color of your reaction so you can actually directly, correlate the change in the color of your, test with, the presence and quantity, of the biomarker, you want to detect, specificity. Comes in the fact that if only one of these probes bind then, it's not enough to generate a signal so you need to have a full kind, of binding of two molecules, binding, to two different parts of the same biomarker. To actually have a signal. Which you can detect which, highlights the kind of specificity we, need for, risk analysis, so. Once you have a technology with. Cottagey, which you want to test we made with molecules and when we test them on biomarkers. Which were identified, as being, good, diagnostic. Biomarkers for, prostate cancer and when, we test them in vitro so, we do some experiments, like both ones I won't go into the details but basically making sure that our assay, is quantitative. So, we can know how much of it biomarker, is present, but, it is relatively fast if, it's a kind of a blood test which is going to be done in the GP clinic you don't want to be waiting for three hours to get the results and also. Specific, so you want to make sure that the signal you get is highly, specific to the biomarker, you want and not from the junk which is present also in your blood. So. That's what we've done there. Was very kind of good encouraging, results but, is this technology fit for purpose is, good to do things in vitro and, kind of the small kind of a glass vials but what happens if you actually apply it to kind of clinical, samples, so, this is where again collaboration. With cancer biologists, a clinician takes place they, have access to kind of to, kind of patient. Samples and we can actually test our technology, to make sure we can actually do. What, we are trying to do in this case we, had kind, of blood. Samples from four different categories of patient, patient. We had prostate, cancer had, the prostate removed and, were in remission. People. We had kind, of prostate cancer had. Been treated but still had their prostate but, also are in remission people. We have localized, advanced tumor and the, most advanced, metastatic advanced. Tumor so we had some holes on these four categories and we try to use our probe to see if we could discriminate which, we with four different categories so. This is over two different biomarker. And without. Going into the details, we, you, can see that we were able to discriminate between, patients, wearing remission and patient. We actually had an active form of prostate cancer and, could, even discriminate, between people, with a localized, tumor animal. Metastatic. Cancer. And we. Had a good correlation between our new technology and the gold standard which other said is, reasonably. Good but, not amenable to, kind, of public. Screening a point-of-care testing. So. What, was a good point we. Design. Strategy, tested, it in vitro and then, tested, it on pure. Human, patient, we, saw that it was fit for purpose, amplification.

Free Good correlation, and we could do diagnosis, and grading, of prostate cancer so. Already. Kind of a great achievement for us but how. Do we go of and from bench to bedside all. Over technology have talked about requires. Manipulating. Solution, making probes is not really a blood test a point of care a screening, test so. What we try to do and again I'm going to go back quickly with a comparison, with the kind of. With. Pregnancy. Test we, try to use a very low kannathil. Matrix. To. Actually kind of template for, our device and what's. Cheapest. Advair. Paper, is one, of the kind of cheapest material you can find to, actually house your. Technology. So, this is roughly the way a pregnancy, test would work about going to the details but, you load the sample, which, you want in our case blood at the end of a device is basically going to kind of travel the paper will absorb the fluid is, going to travel from. The left to the right because at the right you have some kind of absorbent, paper which, is basically kind of soaking up all of a liquid to make it travel from the left to the right hand side and. Then. At some point you have your, sensor, which is incorporated in, specific, lines that, mean is going to be able to capture you, biomarker, and generate, a signal, so you can actually on each of this line, in here on your test detect. Whether the biomarker, you're looking at is present, and, at which under. Which quantities, so. I will skip bad but basically that's. How we try to translate RSA, into, a lateral flow paper this, is the blood that contain you biomarker, this, is the kind of capture. Probes or the probe which is going to capture your biomarker. When it travels through the paper and this. Is the over part of a system which, is going to be the piece of paper going. To be kind of carried away by the blood and also cannot generate direction. Right. So. This is basically. Roughly, how it look these, loops this. Is a scanned image of your paper and you see here you've got the test line that, tells you the darker, the test line is the, more of a biomarker, of interest, you've been able to detect I've, showed you an example here, we've only one line but you can potentially have multiple, multiple, lines but they take multiple, biomarkers in. One single, assay which, again will increase the, specificity of, your. Test. Right. Last, couple of slides because I'm probably kind of going to run out of time is, basically. Everything. I've said in here is basically, and. I talked about the blood test but. At, the moment we can't really directly. Go from. Blood to. The, assay we, still have to kind of process the blood because, the blood contains, too much too, much junk, as far as the diagnostic, test is concerned to actually go directly blood, on paper to, the Diagnostics, so those are, going to be the standard procedures, we do for this kind of test we take the blood we, kind of spin it down in a centrifuge to separate the serum and then we do a lot of kind of chemical treatment, to do the isolation, of the biomarker, before we do a detection, obviously. You, can easily see that this is not, kind, of great, for public, screening, so, what we try to do is to find ways to go directly from, the blood to the detection and.

Bypassing. All of these very complex, labor-intensive. Steps, that require qualified. Clinician to actually, do. Them. One. Going to be detail of that but, that's basically the, approach we. Are chipping in highly. Simplified ways. So starting. From the left to the right these. Are basically all of the main components, you, would find in, your blood, so. That goes from kind of lymphocytes. Can offer right blood cells, platelets. Proteins. So, all of these things that can really remain constituent, of your blood and, here. In the bottom are basically, the, RNA biomarker. Which were using for our Diagnostics, in, terms of size these, RNA. Nucleic, acids are the, smallest molecular. Component, of blood everything. Else we see the scale of size all of those are orders of magnitude, larger in size than the biomarker, we want to, detect so, the strategy, we're using in here is trying to basically doing, some size exclusions, it's like using a molecular sieve. You. Put your blood on it everything, which is too big is going to remain trapped within the mesh of your sieve and only. Your small biomarker, will be small enough to pass through and then, be, reacting. With, your probe for, the detection so, we're not using a sieve to do that but we basically. Designing. An engineering, and material which, is like hydrogenated. Materials, which, will allow, us to do that in an automated fashion. Once. We've done that and this is my last slide before the knowledge Minh is basically. Trying, to find ways to combine all, of these different types, of research we've done in actually, one single. Use a low-cost. Chip. So. The. Last part I've said which, is the kind of molecular sieve is, basically, for the denaturation and, extraction, of a biomarker from blood the. Upper part of started wave is the sensing, detection, is how we can use paper and. Molecular. Probes to detect these biomarkers, then we have to find a way to combine the two into a single kind, of device, so, we can do that by either kind of having two separate, kind. Of entities, in here or merging, them into one single paper, strip we've, always the end goal of kind of using this trip into a small machine and then, get the readout directly, in an, hour, or so within the GPS clinic. Right. So. Just. Before I conclude. Acknowledged obviously, all of the people we've contributed when we're on another to. This. Work, so both awakened a PhD, student we've, been working in different aspects of these projects, and obviously. As I said collaborators. And I think this is one of the main kind of highlight of this kind of talks, is this. Work is only possible if we can actually kind, of have, some input from people we are actually directly dealing with patient, some people will never biology, behind it and basically, both all the collaborators, which, have. Contributed or, are kind of contributing, to this project which, is currently funded by Cancer Research okay thank. You very much for your attention.

2019-02-07 14:14

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