font-family: CopernicusBold,sans-serif; By conjugating luciferase protein to quantum dots, bioluminescence resonance energy transfer (BRET) turns . Luciferase in And Bill Gates Quantum Dot Tattoo "The Vaxxed Glow with Black UV light The Light Bringer . } } All imaging was performed using the Camera FV-5 Lite app (FGAE Studios). .page-body__content h1 {font-size: 2.75rem; margin-bottom: 1rem; font-family: CopernicusMedium,serif; color: #00205B;} The researchers designed their dye to be delivered by a microneedle patch rather than a traditional syringe and needle. Parents often dont know their childrens vaccination histories, McHugh said. The researchers also tested the vaccination strategy in rats, using microneedle patches that delivered the quantum dots along with a polio vaccine. But the researchers have already tried it out on rats and found that the patterns were still detectable nine months after injection. .page-body__content p a {color: #3455DB; text-decoration: none; border-bottom: 2px #00205B dotted;} (G) SEM image of a dissolvable microneedle array based on the geometry shown in (C). In the real world use case, this automated classification will eliminate classification subjectivity that could interfere with the accuracy of this approach. QDs with a copper indium selenide core and aluminum-doped zinc sulfide shell were tuned to emit in the NIR spectrum by controlling stoichiometry and shelling time. Theyre like putting on a bandage.. 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. Bethesda, MD 20894, Web Policies .article .article__body figure.align-right {margin: 0 0 20px 30px} He YP, Hong C, Li J, Howard MT, Li Y, Turvey ME, Uppu DSSM, Martin JR, Zhang K, Irvine DJ, Hammond PT, Synthetic Charge-Invertible Polymer for Rapid and Complete Implantation of Layer-by-Layer Microneedle Drug Films for Enhanced Transdermal Vaccination. 111 0 obj <>stream (H) Total anti-poliovirus type 2 IgG antibody titers and (H) neutralizing poliovirus type 2 antibody titers showing no differences after three doses of type 2 inactivated poliovirus vaccine delivered via subcutaneous injections or microneedles with or without PMMA-encapsulated QDs, n=5. @media (max-width: 64em){ Slider with three articles shown per slide. In this case, the quantum dots are copper-based, and designed to emit near-infrared light. Formative studies in which users test the devices, including the packaging and labeling, will need to be conducted to improve components for commercialization and to manufacture devices for testing in human studies. Based on immunohistochemical observations, the proliferating cell nuclear antigen (PCNA)-negative area of tumor sections after BRET-mediated PDT was obviously increased compared to the PDT-untreated groups without an external light source. 7A). Cropped, but otherwise raw, smartphone images collected from a fixed distance showing the intradermal NIR signal from PMMA-encapsulated QDs delivered via microneedle patches on rats 0, 12, and 24 weeks after administration. Knowledge awaits. Note: Scale bars in NIR-filtered images are approximate with (J, L, N, P) taken at about the same distance. S2. The average grayscale intensity of the remaining pixels was subtracted to generate longitudinally comparable values for signal-above-background. .article__body ul a:hover { 0000004430 00000 n We then sought to test the in vitro and in vivo biocompatibility of our QDs. The patch can be customized to imprint different patterns that correspond to the type of vaccine delivered. Different people and different cultures will probably feel differently about having an invisible medical tattoo.. .views-exposed-form { Arendt-Nielsen L, Egekvist H, Bjerring P, Pain following controlled cutaneous insertion of needles with different diameters. .article--story h1.article__title {font-size: 2.5rem; line-height: 3rem; margin-bottom: 1.5rem;} display: none; Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. Federal government websites often end in .gov or .mil. QD-containing microparticles were then embedded in dissolvable microneedles and administered to rats with or without a vaccine. 0000027694 00000 n Fields VS, Safi H, Waters C, Dillaha J, Capelle L, Riklon S, Wheeler JG, Haselow DT, Mumps in a highly vaccinated Marshallese community in Arkansas, USA: an outbreak report. As many as two-thirds of opportunities to vaccinate may be missed in some areas (11), leading to a potential 30% drop in vaccination coverage (3). display: block; } Images of a 16-needle microneedle patch containing PMMA-encapsulated QDs were collected with the adapted smartphone under ambient indoor lighting (C) without the 850 nm long-pass filters and (D) with the pair of 850 nm long-pass filters under LED illumination from the same distance. LUCIFERASE-IMMOBILIZED QUANTUM DOTS | DNA TATTOOING - YouTube These components would add cost, complexity, and size, which are undesirable for distributed mobile use. In this study, Renilla luciferase-immobilized quantum dots-655 (QD-RLuc8) was used for bioluminescence resonance energy transfer (BRET)-mediated PDT to resolve these problems. A 2 mm-thick piece of pigmented human cadaver skin from donors age 2168 years who self-identified as African American was overlaid onto the sample to recapitulate light absorption by tissue above an intradermal fluorophore. table.blueTable td, table.blueTable th { official website and that any information you provide is encrypted They also can test how slight variations in the spike protein may influence SARS-CoV-2s behavior. 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. text-underline-offset: 1.5px; In human cadaver skin models, the patterns outlasted five years of simulated Sun exposure. 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. In (B, D, F), zero and one hundred represent the worst and best values, respectively, for each parameter for between 0 and 1. Their near-infrared dye is invisible, but the pattern they set can be read and interpreted by a customized smartphone. 6Google, 355 Main St, Cambridge, MA 02142. font-size: 1.15rem; Alternatively, encapsulated QDs showed a much higher transfer of fluorescence into the skin that resulted in a NIR signal that was 10-fold higher than unencapsulated QDs (Fig. 0000152007 00000 n 0000031433 00000 n The two pictured here are about 10 nanometers in diameter, about 3,000 times smaller than the width of a human hair. These optics were fit into a 3D-printed phone case customized for SM1-threaded components (1.03540) to fit with commercially-available optical components. This spacing was sufficiently large to allow each needle to act independently and thereby allow force requirements to scale linearly with needle number (37). Science Translational Medicine (2019)]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. %PDF-1.4 % .resize500 img { max-width:500px; } Karen Weintraub is a staff writer at USA Today, where she covers COVID, vaccine development and other health issues. .page-body__content h5 {font-size: 1.75rem; margin-bottom: .5rem; font-family: CopernicusMedium,serif; color: #00205B;} The quantum dots after being administered to the skin of rodents. However, clinical implementation of QDs has been stymied by the toxicity of their core elements, such as cadmium and lead (23). Manual ISO and shutter speeds were necessary to enable longitudinal comparison. Representative histological samples collected from rats receiving microneedle-delivered PMMA particles containing S10C5H QDs (B, C) one day, (D, E) two weeks, and (F, G) four weeks after administration stained with hematoxylin and eosin or Massons trichrome, respectively. Langer and Jaklenec are co-corresponding authors of the teams published paper in Science Translational Medicine, which is titled, Biocompatible near-infrared quantum dots delivered to the skin by microneedle patches record vaccination., Vaccines save an estimated 23million lives every year, but another 1.5 million vaccine-preventable deaths occur each year due to undervaccination, primarily in developing countries, the authors commented. We chose to use a 780 nm LED rather than a laser because of the reduced cost, safety concerns, and maintenance combined with improved portability. 200 L of PBS was then added to each well and the samples were incubated at 37C for 24 hours. 0000024059 00000 n To enable the imaging of NIR QDs in a field setting, we designed an inexpensive, smartphone-based imaging system. In our experience, training AlexNet with 5,000 synthetic images yielded a real-world data classification accuracy of 92% for the circle and 97% for both the cross and rectangle. K.J.M., S.Y.S., C.F.P., F.L., M.P., N.P., and A.K. Prior to loading, PDMS molds were treated with air plasma using a Harrick Plasma Cleaner PDC-091-HP on high power at 500 mTorr for 1 min. .page-body__content figure.align-right {margin: 6px 0 30px 30px;} Luciferase - Wikipedia Author contributions: K.J.M., R.L., A.J., L.W., and P.A.W. .article__main-image { Every year, a lack of vaccination leads to about 1.5 million preventable deaths, primarily in developing nations. display: inline;} @media only screen and (max-width: 64em){ In order to be protected against most pathogens, one needs multiple vaccinations, Jaklenec said. Shall we continue in sin, that grace may abound?2 God forbid. and transmitted securely. .article .date {color: #44474F;} Next, to test the longevity of QD-containing PMMA microparticles in vivo, we administered patches containing eight microneedles in one of three distinct patterns: A circle on day 0, a cross on day 28, and a rectangle on day 56 and performed longitudinal imaging over nine months (Fig. Thank you for visiting nature.com. 0000005830 00000 n } display: inline-block; 0000009528 00000 n Histological examination of the local tissue response revealed tissue damage consistent with needle penetration one day after administration (Fig. Imaging a QD-loaded microneedle patch with and without the long-pass emission filters demonstrated the ability to filter background light while retaining NIR QD signal transmission (Fig. Discover world-changing science. In the future, custom auto-exposure settings could be implemented to automate this process. Decreasing the spacing of microneedles from 3.23 mm to 1.57 mm (11 cm and 0.50.5 cm patch sizes, respectively) did not affect the amount of force required for penetration (Fig. This is also supported by qualitative images shown in Fig. text-transform: uppercase; devised the concept, K.J.M., L.J., R.L., and A.J. Synthetic data could also be produced using image augmentation to train the algorithm without the need for actual patch applications. The two pictured here are about 10 nanometers in diameter, about 3,000 times smaller than the width of a human hair. .article .article__breadcrumbs span:not(:first-of-type) {color: #005B50;} In the meantime, to ensure continued support, we are displaying the site without styles Munich Quantum Valley formally founded as an association | Max-Planck Adapting a laser to this setup would have required a diffusor or beam splitter to spread the light, safety mechanisms, and potentially some type of cooling apparatus. The researchers now plan to survey health care workers in developing nations in Africa to get input on the best way to implement this type of vaccination record keeping. 0000006934 00000 n These procedures were repeated 4 and 8 weeks later to provide rats with second and third doses. But obviously, we didnt want to give people a scar, she says, noting that her team was looking for an identifier that would be invisible to the naked eye. Evolution of fluorescence emission properties with shelling time, Fig. background: #f3f3f3; 0000010192 00000 n Bethesda, MD 20894, Web Policies The dots are about 4 nm in diameter, and are encapsulated in biocompatible microparticles that form spheres about 20min diameter. An official website of the United States government. Thats really the biggest challenge that we overcame in the project, Jaklenec says, adding that the team tested a number of off-the-shelf dyes that could be used in the body but could not find any that endured when exposed to sunlight. Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR, The Nuts and Bolts of Low-level Laser (Light) Therapy. Nat. The same steps was performed for ZnS:Al-coated CuInSe2 QD solutions at 10 mg/mL in toluene. hb````4a`g`bb@ !6(~_` 0. Fellowship support for K.J.M. The text at the bottom of each image indicates the image collection settings ISO density and shutter speed (SS) in seconds. Keeping track of a childs shots could be so much easier with technology invented by a new Rice University professor and his colleagues. display: inline;} .form-actions { display: flex; } 8600 Rockville Pike This approach is likely to be one of many trying to solve the problem of storing individuals medical information, says Ruchit Nagar, a fourth-year student at Harvard Medical School, who also was not involved in the new study. Keywords: SARSCoV2; antivirals; influenza pandemic; nanomaterials; quantum dots. } This website is managed by the MIT News Office, part of the Institute Office of Communications. .article--story h1.article__title { } An appreciable amount of a particular light source is a key to activate photosensitizers in PDT. Microneedles are embedded in a Band-Aid-like device that is placed on the skin; a skilled nurse or technician is not required. Such a system of recording medical information must be extremely discreet and acceptable to the person whose health information is being recorded and his or her family, he says. Internet Explorer). .page-body__content p a:hover {font-size: 1.125rem; color: #697E2F; text-decoration: none; border-bottom: 2px #697E2F solid;} Bioluminescence is widely used for in vivo imaging of nude mice. They are also exploring ways to exploit modulation of the BRET signal to detect enzyme or protein function. GERMANY: Munich Quantum Valley - Doctoral Fellowship Programme - EURAXESS 0000279443 00000 n 5, ,DDI). 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. 239000002096 quantum dot . and D.V. padding: 1em 2em; 1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139. line-height: 1.5; Keeping track of vaccinations remains a major challenge in the developing world, and even in many developed countries, paperwork gets lost, and parents forget whether their child is up to date. This self-quenching property is problematic for this microneedle-delivered recording system because it limits the packing density of the dye, and thus its brightness. Gill HS, Denson DD, Burris BA, Prausnitz MR, Effect of microneedle design on pain in human subjects. .page-body__content ul li {font-size: 20px;} From these simulations, a value of 0.5 was selected for alpha. For each animal and time point, approximately 20 images were collected with slightly different aim of the LED, which was controlled independently from the camera that remained in a fixed location. Because once they inject this thing into your hand. S7. We build quantum computers in Bavaria and make them accessible to users. The two-year project is aimed at the 1.5 million preventable deaths that result from a lack of vaccinations, primarily in developing nations. S3. background-color: #44474F; 5Global Good, Intellectual Ventures Laboratory, 14360 SE Eastgate Way, Bellevue, WA 98007. article.align-right {margin: 0 0 20px 30px} 0000125860 00000 n Using aqueous in situ polymerization on a bioluminescent enzyme anchored with polymerizable vinyl groups, we obtained nanosized core . This may result in the application of additional, unnecessary vaccine doses and therefore undue cost or, more problematically, missed opportunities to vaccinate, which leaves the child at risk for contracting infectious diseases (8,10). .article__main-image {text-align: center; padding: 2em; display: none;} margin: 0 1em; Samples were sectioned and stained with hematoxylin and eosin or Massons trichrome. First, is that you dont administer unnecessary vaccines, which has a cost. table.blueTable tfoot .links a{ 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). 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. A new technology uses light to activate proteins inside & outside of cells. Matsuo K, Yokota Y, Zhai Y, Quan YS, Kamiyama F, Mukai Y, Okada N, Nakagwa S, A low-invasive and effective transcutaneous immunization system using a novel dissolving microneedle array for soluble and particulate antigens. In addition, histological images demonstrated that microneedle-delivered particles were delivered to a depth similar to professional tattoos (47), which supports their potential for long-term NIR detection. To the left is a human cell (gray) studded with the ACE2 receptors (blue) that those viral spike proteins bind to before SARS-CoV-2 enters and infects our cells. They dont go very deep, which makes them theoretically painless and a lot easier for kids, McHugh said. He runs a company, called Khushi Baby, that is also trying to create a system for tracking such information, including vaccination history, in the developing world. 0000148437 00000 n 0000018201 00000 n Important design criteria were to provide ample resistance to mechanical failure while also achieving a high deliverable volume, defined as the volume near the dissolving microneedle tip. At predetermined time points, samples were removed from light and imaged using a custom NIR-imaging platform consisting of a 500 mW laser emitting at 808 nm and TE-cooled mount powered by a LDC210C Laser Diode Controller and TED200C Temperature Controller, a 15x achromatic Galilean beam expander, protected silver mirror, 850 nm color glass long-pass emission filter, and a high-sensitivity USB 3.0 CMOS Camera (DCC3240N) affixed to an optical breadboard (Thor Labs) inside a dark work enclosure (U.S. Laser). Luciferase: Quantum Dot Tattoo & the Seething Energies of the Light These needles are slightly smaller in diameter than a 30-gauge needle and therefore should minimize both pain and the force required for skin penetration (36). Loizidou EZ, Williams NA, Barrow DA, Eaton MJ, McCrory J, Evans SL, Allender CJ, Structural characterisation and transdermal delivery studies on sugar microneedles: Experimental and finite element modelling analyses. Hair removal was performed prior to microneedle administration by shaving the rear flank with an electric razor and applying depilatory cream for about 2 min. 0000002176 00000 n Longitudinal in vivo imaging using a smartphone adapted to detect in the NIR demonstrated that microneedle-delivered QD patterns remained bright and could be accurately identified using a machine learning algorithm nine months after application. In one embodiment, the microneedle patch contains both vaccine and dye pigments to administer vaccine and record such administration in one application of the microneedle patch. Several years ago, the MIT team set out to devise a method for recording vaccination information in a way that doesnt require a centralized database or other infrastructure. 2F). All photobleaching data is reported as simulated days of exposure based on a 12-hour light/dark cycle. Thanks for reading Scientific American. Great article, got a firm knowledge about drug discovery. 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. text-align: right; Inset shows an image at a higher exposure. Box 1892, Houston, TX 77251-1892 |, 713-348-0000 | Privacy Policy | Campus Carry, Cancer Prevention and Research Institute of Texas. The maximum bioluminescence intensity of Rluc (2 M) is observed at 480 nm, which increases with increasing the amount of . article.align-center {margin-right: auto; margin-left: auto; display: table;} It doesnt tell you anything else about the person., The square-centimeter patches hold up to 16 tiny needles. Molds were then left at room temperature in a laminar flow hood as an initial drying stage. background: #0A509E; Data was smoothed using an eleven-frame moving window and plotted as a histogram with 300 equal-sized bins ranging from 2.1 to 59.9 m. When the patch is applied to the skin, the microneedles, which are 1.5 mm long, partially dissolve, releasing their payload within about two minutes. 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. They . text-align: left; The systemwhich has not yet been tested in childrenwould provide quick and easy access to vaccination history, avoid the risk of clerical errors, and add little to the cost or risk of the procedure, according to the study, published Wednesday in Science Translational Medicine. The number of marks per pattern at this time was 7.3 0.8, which was largely independent of the spatial distribution of microneedles at the time of administration [7.4 0.8, 7.2 0.8, and 7.4 0.8 for the circle, cross, and rectangle, respectively] (Fig. padding: 25px 25px 0px; Microneedles were applied using a spring-loaded applicator and held in place for two minutes to allow for partial dissolution. Given the minimal training data used, it was important that images were collected using settings that roughly approximated the range of brightness/signal spread of images used for training. 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. Blue light, however, does not penetrate tissue well and also produces high background owing to excitation of endogenous fluorophores. Credit: Nick Higgins. Epub 2023 Mar 2. Bioluminescence resonance energy transfer using luciferase - PubMed .article__body h3 {font-size: 2.25rem; margin-bottom: .75rem; font-family: CopernicusMedium,serif; color: #00205B;} Commercial dye and custom quantum dot characterization. (A) Fluorescent microparticles are distributed through an array of dissolvable microneedles in a distinct spatial pattern. font-family: CopernicusMedium,serif; CAS There are so many aspects to this particular project that we need nanotechnologists, bacteriologists, chemists and computer scientists, he said. 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. margin: 0 0 .5em 0; } 4, ,IIL) and pigmented human skin (Fig. .alert { By using a microneedle form factor, this platform should easily assimilate into the future vaccination landscape, since microneedles are currently in development for several vaccines (15) and have shown advantages such as antigen dose-sparing, improved antigen stability, and ease of (self-)administration compared to traditional soluble injections (1618). } Black RE, Cousens S, Johnson HL, Lawn JE Without accurate vaccination records, healthcare professionals lack the data to make informed decisions about administering vaccines, often relying on parental recall (10). The resulting particles were resuspended in deionized water and measured using a Multisizer 3 (Beckman Coulter) with a 100 m aperture. Because the 1.5-millimeter needles disintegrate in the skin, no biohazardous sharps remain for disposal, he said. font-size: 1.25rem !important; L.J., H.S.N.J., and W.T. The large size of microparticles (15.7 5.3 m) was also hypothesized to minimize clearance because previous studies have shown that larger particles are more resistant to clearance by macrophages, the most relevant cell type for clearing foreign material (28). /* Table */ display: flex; padding: 20px 15px 20px 50px; At both later time points, there appeared to be a small number of macrophages and foreign body giant cells at the site of administration. Tests using human cadaver skin showed that the quantum-dot patterns could be detected by smartphone cameras after up to five years of simulated sun exposure. text-underline-offset: 1.5px; These studies were designed to evaluate the suitability of intradermal near-infrared fluorescent microparticles as a reliable, long-term detection method. Finite element analysis identified that microneedles with diameters of 100 or 200 m were prone to failure due to both bending and axial loading, therefore all subsequent studies used needles 300 m in diameter. Approximately 300 L of a 17% w/v sucrose and 17% w/v PVA solution in water was then dispensed on top of the mold and centrifuged at 3,234 RCF for 5 min. This site needs JavaScript to work properly. .views-exposed-form { 5B). Thinking Revelations the mark of the beast to buy, sell, trade This world is doomed, eventually, no matter what we do or dont do. For example, in one QD formulation, performing the shelling process for 5 hours resulted in an increase PL QY from 16.2% to 43.6% and a blue shift in the emission peak from 964 nm to 891 nm. text-underline-offset: 1.5px; Self-illuminating quantum dot conjugates for in vivo imaging. The plate was then read using a Tecan Infinite M200 Spectrophotometer Alexa Fluor 790 (784/814 nm ex/em), DyLight 800 (760/810 nm ex/em), IRDye 800CW (768/798 nm ex/em), IR-820 (710/820 nm ex/em), Sulfo-Cyanine7 (750/773 nm ex/em), VivoTag 800 (785/815 nm ex/em), and indocyanine green (805/835 nm ex/em). M.S. Briefly, 150 mg of oleic acid-functionalized QDs and 100 mg of PMMA were dissolved in 2 mL of dichloromethane. Despite being heavily protected from light by overlying human skin, organic fluorophores photobleached within a few weeks of simulated sun exposure (Fig. This encapsulation allows the dye to remain in place, under the skin, after being injected. 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. These self-illuminating quantum dot conjugates can be prepared by coupling of commercially available carboxylate-presenting quantum dots to the light-emitting protein Renilla luciferase. font-size: 1.25rem; No fibrous encapsulation was observed over the time points collected, supporting the biocompatibility of the microparticles. This article exclusively discusses the potential role of QDs as biosensors and antiviral agents for attenuation of viral infection. } If you have comments or questions not related to the current discussions, please direct them to Ask NIH. For all photobleaching experiments, skin was replaced every 24 days to reduce the effects of melanin degradation. Nevertheless, microneedle-treated groups yielded total and neutralizing antibody titers against IPV2 that were similar with theoretical dose-matched subcutaneous injections and were above the threshold known to confer protection in humans, regardless of the presence of encapsulated QDs. (F) Photoluminescence quantum yield as a function of shelling time under different excitation wavelengths. | The Munich Quantum Valley (MQV) is an association of the Bavarian . font-size: 1.25rem; 0000009589 00000 n MeSH Alternatively, QDs performed very well under light exposure and have a larger Stokes shift, which enables them to avoid substantial reabsorption and therefore be used in a densely packed format. This experiment was repeated three times with one replicate each. color: #034ea1;