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To enable the imaging of NIR QDs in a field setting, we designed an inexpensive, smartphone-based imaging system. .page-body__content p {font-size: 1.125rem; padding-bottom: 1.5rem;} Ana Jaklenec, a research scientist at MITs Koch Institute for Integrative Cancer Research, and Robert Langer, the David H. Koch Institute Professor at MIT, are the senior authors of the paper. Vassilieva EV, Kalluri H, McAllister D, Taherbhai MT, Esser ES, Pewin WP, Pulit-Penaloza JA, Prausnitz MR, Compans RW, Skountzou I, Improved immunogenicity of individual influenza vaccine components delivered with a novel dissolving microneedle patch stable at room temperature. The pH stability of S10C5H QDs in PMMA was determined by casting a solution onto the bottom of a plate to prevent agitation upon addition of the buffer. We conclude that this nanotechnology-based PDT possesses several clinical benefits, such as overcoming light penetration issues and treating deeper lesions that are intractable by PDT alone. Gorshkov K, Susumu K, Chen J, Xu M, Pradhan M, Zhu W, Hu X, Breger JC, Wolak M, Oh E. ACS Nano. To determine the optimal microneedle geometry for this application, finite element analysis was performed. Concerns have been voiced about the ability of quantum dots to function as fluorescence resonance energy transfer acceptors for organic fluorophores. By conjugating luciferase protein to quantum dots, bioluminescence resonance energy transfer (BRET) turns . McHugh plans to continue his work on the technology at Rice. .page-body__content h1 {font-size: 2.75rem; margin-bottom: 1rem; font-family: CopernicusMedium,serif; color: #00205B;} } 0000027530 00000 n Thats not science fiction. 2023 Scientific American, a Division of Springer Nature America, Inc. By selectively loading microparticles into microneedles, the patches deliver a pattern in the skin that is invisible to the naked eye but can be scanned with a smartphone that has the infrared filter removed. After 1 h incubation, plates were washed another 5 times and then 100 l of a SIGMAFAST OPD substrate (Sigma-Aldrich) was added after resuspension according to the manufacturers protocol. 0000151738 00000 n (L) Graph showing the average probability of the machine learning algorithm (all patterns correctly detected), n=5. The area was then rinsed to remove excess hair, sterilized using an ethanol swab, and allowed to dry. Now Jianghong Rao, Sanjiv Gambhir and colleagues from the Molecular Imaging and Bio-X Program for interdisciplinary research at Stanford describe the synthesis and the use of bioluminescent quantum dots for in vivo imaging. In this issue, So et al. Just one year after the Bavarian state government issued its declaration of intent, a memorandum of understanding was signed ceremonially at the Ba-varian Academy of Sciences and Humanities to mark the formal establishment of the Munich Quantum Valley. (F) PL profiles of S10C5H QDs before and after PMMA encapsulation showing a minimal shift in fluorescence emission wavelength. Federal government websites often end in .gov or .mil. Samples were then placed under a 300W PV Cell Testing Solar Simulator Model 16S-300002 (Solar Light). } Further, because there was no trend towards lower machine learning classification probability at three, six, and nine months, it appears that the patterns are stable after an acute period of signal loss, which is also supported by short-term quantitative data and long-term qualitative data. This experiment was repeated three times with one replicate each. thanks the Youth Innovation Promotion Association CAS (2018042), National Natural Science Foundation of China (81671755), and China Scholarship Council (201604910444) for financial support. If we dont have good data, its really difficult to eradicate disease, explains research scientist Ana Jaklenec. The as-synthesized PbS QDs exhibited photoluminescence in the range of 800-1050 nm, and the Luc8 enzyme remained active within the Luc8-PbS complex. padding: 1em 2em; Tzeng SY, Guarecuco R, McHugh KJ, Rose S, Rosenberg EM, Zeng Y, Langer R, Jaklenec A, Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release, Ternary I-III-VI quantum dots luminescent in the red to near-infrared. .article__body h2 {font-size: 2.5rem; margin-bottom: 1rem; font-family: CopernicusMedium,serif; color: #0A509E;} 0000025837 00000 n [1] color: #034ea1; The accumulation of macrophages observed around the particles was less than other studies have shown for poly(lactic-co-glycolic acid) microparticles (45), for example, which are present in many FDA-approved drug delivery systems (46). 0000181366 00000 n To establish this system, we synthesized, encapsulated, and delivered cadmium- and lead-free photostable QDs into the skin using a custom microneedle array, adapted a smartphone to create an inexpensive NIR imaging system, and demonstrated the ability to accurately detect patterns in vivo for a period of 9 months using a semi-automated machine learning algorithm. .article .article__body figure.align-left {margin: 0 30px 20px 0;} .h3, h3 { But the researchers have already tried it out on rats and found that the patterns were still detectable nine months after injection. Because once they inject this thing into your hand. 0000125059 00000 n According to a Scientific American story, the project came about following a direct request from Microsoft founder Bill Gates himself, who has been personally involved in efforts to eradicate polio and measles through vaccinations. 6 that depict dimmer signals between 0 and 12 weeks, but no further substantial losses between 12 and 24 weeks. The dye has been shown to. 18 94 Along with them, the team eventually wants to inject sensors that could also potentially be used to track aspects of health such as insulin levels in diabetics, Jaklenec says. S5). n=3, *P < 0.05, ***P < 0.001, ****P < 0.0001 (two-way ANOVA with Tukeys multiple comparisons). et al. The QD signal stabilizes rather quickly and then presents a fairly consistent SNR at 3, 6, and 9 months, indicating that microparticle clearance likely primarily occurs at early time points (less than three months). Because both excitation and emission light can be absorbed by the body, we needed to create a system where both stages were within the optical imaging window. S1S3, table S2). Adapted smartphone images of pig skin prior to microneedle application (I) without and (J) with 850 nm long-pass filters. } This solution was then added to 50 mL of 1% PVA (88% hydrolyzed, Mw 31,000) solution in water. After considering these factors along with deliverable volume, a microneedle with a 300 m-wide cylindrical base that was 750 m in height with an upper cone 750 m in height was selected as a leading candidate for further study. } color: #fff; This website is managed by the MIT News Office, part of the Institute Office of Communications. 0000009128 00000 n .article--story h4.article__title { align-items: center; The reaction mixture was heated to 200C and maintained at this temperature for 30 min under the protection of nitrogen. #block-views-block-featured-stories-rice-block-1 { background: #001e6b; padding: 2em 0; } Tests using the platform showed that QDs delivered to samples of human skin were still detectable after photobleaching that simulated five years of exposure sunlight, and they remained detectable for up to nine months when tested in rats. .page-body__content h2 {font-size: 2.5rem; margin-bottom: 1rem; font-family: CopernicusMedium,serif; color: #0A509E;} The reaction mixture was then degassed under vacuum for 20 min, purged with nitrogen for 20 min, and degassed for an additional 45 min at 120C. 0000002802 00000 n In other words, they've found a covert way to embed the record of a vaccination directly in a patient's skin rather than documenting it electronically or on paper - and their low-risk tracking system could greatly simplify the process of maintaining accurate vaccine records, especially on a larger scale. 0000155745 00000 n This is also supported by qualitative images shown in Fig. We hypothesized that information, such as vaccination history, could be encoded invisibly in the skin by applying a distinct pattern of near-infrared (NIR) fluorescent microparticles using a microneedle patch. In areas where paper vaccination cards are often lost or do not exist at all, and electronic databases are unheard of, this technology could enable the rapid and anonymous detection of patient vaccination history to ensure that every child is vaccinated, says Kevin McHugh, a former MIT postdoc who is now an assistant professor of bioengineering at Rice University. This work provides yet another stunning example of how scientists with widely varying expertise have banded togetherusing all the tools at their disposalto forge ahead to find solutions to COVID-19. This work was supported in part by the Koch Institute Support (core) Grant P30-CA14051 from the National Cancer Institute. Keck Microscopy Facility at the Whitehead Institute. They said, We go on vaccination campaigns where people get into Hummers, drive to a rural village, set up a tent and start immunizing people, but they dont always know whos been immunized before and what vaccines are still needed.. background: #054ea1; The necklace uses the same technology as radio-frequency identification (RFID) chipssuch as those employed in retail clothing or athletes race bibsand provides health care workers access to a mothers pregnancy history, her childs growth chart and vaccination history, and suggestions on what vaccinations and other treatments may be needed, he says. 0000003057 00000 n (D) SEM image of PMMA microparticles containing S10C5H QDs. You are using a browser version with limited support for CSS. By conjugating luciferase protein to quantum dots, bioluminescence resonance energy transfer (BRET) turns these useful fluorophores into a new class of bioluminescent probe. color: #697E2F; .article__main-image { The name was first used by Raphal Dubois who invented the words luciferin and luciferase, for the substrate and enzyme, respectively. The invisible "tattoo" accompanying the vaccine is a pattern made up of minuscule quantum dots - tiny semiconducting crystals that reflect light - that glows under infrared light. 0000018594 00000 n By using a microneedle form factor, this platform should easily assimilate into the future vaccination landscape because microneedles are currently in development for several vaccines and have shown advantages such as antigen dose sparing, improved antigen stability, and ease of (self-)administration compared to traditional soluble injections, the researchers commented. Theyre like putting on a bandage.. padding: 9.5em; The Al precursor mixture consisting of 9 mmol of Al(IPA)3, 5.4 mL of 1-dodecanethiol, and 36 mL of ODE was degassed for 20 min and purged with nitrogen for 20 min. One factor that makes vaccination campaigns in those nations more difficult is that there is little infrastructure for storing medical records, so theres often no easy way to determine who needs a particular vaccine. 0000017115 00000 n ISSN 1548-7105 (online) Graphene and its derivatives, graphene oxide (GO) and graphene oxide quantum dots (GOQDs), have recently attracted much attention as bioactive factors in differentiating stem cells towards osteoblastic lineage. font-size: 1.25em; For NIR fluorescence detection, a Nexus 5x smartphone (Google) was stripped of its stock short-pass NIR filter and paired with an 850 nm long-pass color glass filter and an 850 nm long-pass dielectric filter set in a poly(lactic acid) 3D printed phone case (Fig. In addition, we believe that familiarity with the function of these devices will lessen the learning curve to using the phone for NIR imaging in a field setting. Paper vaccination cards or certificates are the most widely used records in the developing world, but are subject to error (8) and possessed by only 60% of all households in low-and middle-income countries (9). 1 describe a clever quantum dot technology that permits improved imaging in . /* Padding */ Additionally, co-delivery with inactivated poliovirus vaccine produced neutralizing antibody titers above the threshold considered protective. Computer code archived publicly accessible. So, M.K. designed and synthesized quantum dots. 1E), enhance the photoluminescence quantum yield (PL QY) (Fig. Careers. A smartphone case was then designed and 3D printed to interface tightly with optical components possessing SM1 threading directly in front of the rear-facing camera. .ckeditor-accordion-container > dl dt > a { In addition, we needed the new filters to block reflected light from LED illumination. They are also exploring ways to exploit modulation of the BRET signal to detect enzyme or protein function. } (C) Short-term study of signal intensity after microneedle application of unencapsulated or PMMA-encapsulated QDs to rat skin, n=4. encapsulation. For this encoding system to be clinically useful, microneedles and NIR microparticles must be biocompatible and, if applicable, maintain the utility of any co-delivered vaccines. Keywords: SARSCoV2; antivirals; influenza pandemic; nanomaterials; quantum dots. Based on histology and longitudinal imaging studies we would not anticipate a substantial decrease in signal within five years after application, however we did not explicitly demonstrate this due to time constraints which exceed the typical life span of our animal model. A credit line must be used when reproducing images; if one is not provided An official website of the United States government. and transmitted securely. Rouphael NG, Paine M, Mosley R, Henry S, McAllister DV, Kalluri H, Pewin W, Frew PM, Yu T, Thornburg NJ, Kabbani S, Lai L, Vassilieva EV, Skountzou I, Compans RW, Mulligan MJ, Prausnitz MR, TIV-MNP 2015 Study Group, The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): randomised, partly blinded, placebo-controlled, phase 1 trial, Engineering Microneedle Patches for Vaccination and Drug Delivery to Skin. My hope is that this scientific work could someday have a significant impact in terms of enabling patients in the developing world to receive the correct vaccines when needed, explains Prof. Robert Langer. Excess solution was cleared from the top of the mold and the solution was allowed to dry leaving behind particles in the tips of the mold. display: inline-block; The vessel was then sealed and sonicated for 1 h at 60C (50). 0000028880 00000 n We then pursued the use of colloidal quantum dots (QDs), also known as semiconductor nanocrystals, as potential fluorescent probes due to their favorable brightness and photostability. [K.J. } The team ended up using a technology called quantum dots, tiny semiconducting crystals that reflect light and were originally developed to label cells during research. An official website of the United States government. 0000181405 00000 n official website and that any information you provide is encrypted By providing all of the requisite information on the patients themselves, and delivering microparticles in the same microneedles as the vaccine, this platform offers several key advantages compared to traditional paper or electronic medical records including: i) the elimination of need for a widely-accessible, yet secure database of patient information; ii) lack of reliance on accurate patient identification and data entry by medical professionals; iii) ability to make rapid determinations of vaccination status; iv) elimination of vaccination fraud; v) capacity for population-level assessment of vaccine coverage; and vi) minimal cost that is feasible to implement in low-resource settings. 0000024059 00000 n Nat Methods 3, 240 (2006). However, investigations in response to recent outbreaks of measles and mumps in the U.S. (5), Australia (6), and Italy (7), have highlighted that poor immunization recordkeeping is not unique to developing nations. M.S. Karen Weintraub is a staff writer at USA Today, where she covers COVID, vaccine development and other health issues. A new technology uses light to activate proteins inside & outside of cells. Characterization of custom synthesized quantum dots, Table S2. border: 1px solid #054ea1; .article__body h5 {font-size: 1.75rem; margin-bottom: .5rem; font-family: CopernicusMedium,serif; color: #00205B;} These QDs were exposed to simulated solar light through pigmented cadaveric skin at seven-fold the intensity of the sun for a period that simulated five years of day/night exposure. Antaris AL, Chen H, Cheng K, Sun Y, Hong G, Qu C, Diao S, Deng Z, Hu X, Zhang B, Zhang X, Yaghi OK, Alamparambil ZR, Hong X, Cheng Z, Dai H. Wilson RH, Nadeau KP, Jaworski FB, Tromberg BJ, Durkin AJ, Review of short-wave infrared spectroscopy and imaging methods for biological tissue characterization. Bioluminescence, due to its high sensitivity, has been exploited in various analytical and imaging applications. Near-infrared fluorescent microparticles administered to the skin via dissolvable microneedle patches can record vaccine delivery. Accessibility MIT researchers have now developed a novel way to record a patients vaccination history: storing the data in a pattern of dye, invisible to the naked eye, that is delivered under the skin at the same time as the vaccine.

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