Application of Thermoresponsive Polymer and Microfluidics to the Development of a Velocity-Dependent Cell-Sorting Microdevice

3rd Place, Denman Undergraduate Research ForumLow-cost velocity dependent cell sorting in 2D is a currently nonexistent technology for cancer research. The development of such a device would enable further research on the treatment of various deleterious cancers, such as Glioblastoma Multiforme (GBM), which metastasize based off the high motility of a single cell. Here we present a low-cost device capable of sorting these cells. Separation would enable development of highly specific therapeutic agents to limit cancer metastasis in patients. This device consists of microfluidics channels situated under microtextured Polydimethylsiloxane (PDMS) coated with the thermoresponsive polymer Poly(N-isopropylacrylamide) (PNIPAM). Cells are seeded on one end of the device and orient themselves parallel to the striations patterned into the PDMS; traveling further across the device over time. At a specific location (determined by velocity of target cells and time passed), low-temperature fluid can be passed through the microfluidic channel below which triggers a selective conformational change in the PNIPAM. This change shifts PNIPAM from nonpolar to polar, causing the polymer to release previously-adhered cells into solution in favor of binding to media. Establishing the PNIPAM layer capable of releasing cells while allowing them to adhere to microtextures on the PDMS involved a multi-step process. First, PDMS stamps are made of varying thickness, then they were placed in a plasma cleaner and exposed to Argon for 1,3, and 5 minutes at 30 Watts, 8-10 MHz, and ~1000microTorr. Then, samples were exposed to N-isopropylacrylamide (NIPAM) via immersion into a polymer solution and via dropping that solution onto samples and baked at 3 hours or 5 hours. Cell detachment analysis, goniometer experimentation, and SEM images showed that a 1 minute Argon gas exposure, with 1 minute of NIPAM immersion and a 3 hour bake yielded the most successful layer that lifted cells without inhibiting the PDMS microtexture. Future work involves optimizing the device to lift all cells exposed to the channel, as well as further corroborating its efficacy.A one-year embargo was granted for this item.Academic Major: Biomedical Engineerin

Precision cancer monitoring using a novel, fully integrated, microfluidic array partitioning digital PCR platform.

A novel digital PCR (dPCR) platform combining off-the-shelf reagents, a micro-molded plastic microfluidic consumable with a fully integrated single dPCR instrument was developed to address the needs for routine clinical diagnostics. This new platform offers a simplified workflow that enables: rapid time-to-answer; low potential for cross contamination; minimal sample waste; all within a single integrated instrument. Here we showcase the capability of this fully integrated platform to detect and quantify non-small cell lung carcinoma (NSCLC) rare genetic mutants (EGFR T790M) with precision cell-free DNA (cfDNA) standards. Next, we validated the platform with an established chronic myeloid leukemia (CML) fusion gene (BCR-ABL1) assay down to 0.01% mutant allele frequency to highlight the platform's utility for precision cancer monitoring. Thirdly, using a juvenile myelomonocytic leukemia (JMML) patient-specific assay we demonstrate the ability to precisely track an individual cancer patient's response to therapy and show the patient's achievement of complete molecular remission. These three applications highlight the flexibility and utility of this novel fully integrated dPCR platform that has the potential to transform personalized medicine for cancer recurrence monitoring

Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy

Cancer therapy; Predictive markers; Translational researchTerapia del cáncer; Marcadores predictivos; Investigación traslacionalTeràpia del càncer; Marcadors predictius; Recerca translacionalPrecision medicine is starting to incorporate functional assays to evaluate anticancer agents on patient-isolated tissues or cells to select for the most effective. Among these new technologies, dynamic BH3 profiling (DBP) has emerged and extensively been used to predict treatment efficacy in different types of cancer. DBP uses synthetic BH3 peptides to measure early apoptotic events (‘priming’) and anticipate therapy-induced cell death leading to tumor elimination. This predictive functional assay presents multiple advantages but a critical limitation: the cell number requirement, that limits drug screening on patient samples, especially in solid tumors. To solve this problem, we developed an innovative microfluidic-based DBP (µDBP) device that overcomes tissue limitations on primary samples. We used microfluidic chips to generate a gradient of BIM BH3 peptide, compared it with the standard flow cytometry based DBP, and tested different anticancer treatments. We first examined this new technology’s predictive capacity using gastrointestinal stromal tumor (GIST) cell lines, by comparing imatinib sensitive and resistant cells, and we could detect differences in apoptotic priming and anticipate cytotoxicity. We then validated µDBP on a refractory GIST patient sample and identified that the combination of dactolisib and venetoclax increased apoptotic priming. In summary, this new technology could represent an important advance for precision medicine by providing a fast, easy-to-use and scalable microfluidic device to perform DBP in situ as a routine assay to identify the best treatment for cancer patients.Ramon y Cajal Programme, Ministerio de Economia y Competitividad grant RYC-2015–18357. (J.M.). Ministerio de Ciencia, Innovación y Universidades grant RTI2018-094533-A-I00 (J.M.). CELLEX foundation (J.M., A.M.). Beca Trienal Fundación Mari Paz Jiménez Casado (J.M.). European Research Council, grant ERC-StG-DAMOC 714317 (J.R.-A.). European Research Council, H2020 EU framework FET-open BLOC 863037 (J.R.-A.). Spanish Ministry of Economy and Competitiveness, “Severo Ochoa” Program for Centers of Excellence in R&D SEV-2020-2023 (J.R.-A.). Generalitat de Catalunya. CERCA Programme 2017-SGR-1079 (J.R.-A., J.S.). Fundación Bancaria “la Caixa”- Obra Social “la Caixa” (project IBEC-La Caixa Health Ageing) (J.R.-A.). Fero Foundation (C.S.). Networking Biomedical Research Center (CIBER). CIBER is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012), with the support of the European Regional Development Fund (J.S.)

The Boston University Photonics Center annual report 2014-2015

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2014-2015 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This has been a good year for the Photonics Center. In the following pages, you will see that the center’s faculty received prodigious honors and awards, generated more than 100 notable scholarly publications in the leading journals in our field, and attracted $18.6M in new research grants/contracts. Faculty and staff also expanded their efforts in education and training, and were awarded two new National Science Foundation– sponsored sites for Research Experiences for Undergraduates and for Teachers. As a community, we hosted a compelling series of distinguished invited speakers, and emphasized the theme of Advanced Materials by Design for the 21st Century at our annual symposium. We continued to support the National Photonics Initiative, and are a part of a New York–based consortium that won the competition for a new photonics- themed node in the National Network of Manufacturing Institutes. Highlights of our research achievements for the year include an ambitious new DoD-sponsored grant for Multi-Scale Multi-Disciplinary Modeling of Electronic Materials led by Professor Enrico Bellotti, continued support of our NIH-sponsored Center for Innovation in Point of Care Technologies for the Future of Cancer Care led by Professor Catherine Klapperich, a new award for Personalized Chemotherapy Through Rapid Monitoring with Wearable Optics led by Assistant Professor Darren Roblyer, and a new award from DARPA to conduct research on Calligraphy to Build Tunable Optical Metamaterials led by Professor Dave Bishop. We were also honored to receive an award from the Massachusetts Life Sciences Center to develop a biophotonics laboratory in our Business Innovation Center

The Boston University Photonics Center annual report 2014-2015

This repository item contains an annual report that summarizes activities of the Boston University Photonics Center in the 2014-2015 academic year. The report provides quantitative and descriptive information regarding photonics programs in education, interdisciplinary research, business innovation, and technology development. The Boston University Photonics Center (BUPC) is an interdisciplinary hub for education, research, scholarship, innovation, and technology development associated with practical uses of light.This has been a good year for the Photonics Center. In the following pages, you will see that the center’s faculty received prodigious honors and awards, generated more than 100 notable scholarly publications in the leading journals in our field, and attracted $18.6M in new research grants/contracts. Faculty and staff also expanded their efforts in education and training, and were awarded two new National Science Foundation– sponsored sites for Research Experiences for Undergraduates and for Teachers. As a community, we hosted a compelling series of distinguished invited speakers, and emphasized the theme of Advanced Materials by Design for the 21st Century at our annual symposium. We continued to support the National Photonics Initiative, and are a part of a New York–based consortium that won the competition for a new photonics- themed node in the National Network of Manufacturing Institutes. Highlights of our research achievements for the year include an ambitious new DoD-sponsored grant for Multi-Scale Multi-Disciplinary Modeling of Electronic Materials led by Professor Enrico Bellotti, continued support of our NIH-sponsored Center for Innovation in Point of Care Technologies for the Future of Cancer Care led by Professor Catherine Klapperich, a new award for Personalized Chemotherapy Through Rapid Monitoring with Wearable Optics led by Assistant Professor Darren Roblyer, and a new award from DARPA to conduct research on Calligraphy to Build Tunable Optical Metamaterials led by Professor Dave Bishop. We were also honored to receive an award from the Massachusetts Life Sciences Center to develop a biophotonics laboratory in our Business Innovation Center

Tissue engineering and regenerative medicine research - how can it contribute to fight future pandemics?

Understanding the pathogenesis of viral infection is of paramount importance for the development of better therapies. In the particular case of COVID-19, the mechanism of infection is highly complex and involves a critical cascade of events, which can lead to the death of the patient. Intense research is currently being performed to gain mechanistic insights about the virus etiology and to evaluate new therapeutic approaches. The development of point-of-care diagnostic tools, predictive drug screening platforms, and biomimetic models of the disease could play a key role in understanding the cellular and molecular mechanism of viral infection and its response to drugs. In this regard, specific tissue engineering and regenerative medicine approaches, such as microfluidics and organ-on-a-chip technologies, as well as bioprinted in vitro disease models, could be used to develop a technological platform to fight COVID-19, and other virus pandemics yet to come. Herein, we briefly discuss about how such approaches can contribute to address current and future viral pandemics by highlighting recent successful examples.D. Caballero acknowledges the financial support from the Portuguese Foundation for Science and Technology under the program CEEC Individual 2017 (CEECIND/00352/2017) and the project 2MATCH (02/SAICT/2017 - nº 028070) funded by the Programa Operacional Regional do Norte supported by FEDER. M. Carvalho would like to acknowledge IET Harvey Research Prize 2017. The authors also acknowledge the financial support from the EU Framework Programme for Research and Innovation Horizon 2020 on Forefront Research in 3D Disease Cancer Models as in vitro Screening Technologies (FoReCaST- no. 668983), the Portuguese Foundation for Science and Technology (FCT) distinction attributed to J. M. Oliveira (IF/00423/2012, IF/01285/2015) and FCT, Fundo Europeu de Desenvolvimento Regional (FEDER) and Programa Operacional Competitividade e Internacionalização (POCI) for funding the projects B-Liver (PTDC/EMD-EMD/29139/2017), Hierarchitech (M-ERA-NET/0001/2014) and 3BioMeD (JICAM/0001/2017)

Digital Nucleic Acid Detection Based on Microfluidic Lab-on-a-Chip Devices

Microfluidic lab-on-a-chip (LOC) technologies have been developed as a promising alternative to traditional central laboratory-based analysis approaches over several decades due to the capability of realizing miniaturized multiphase and multistep reactions. In the field of nucleic acid (NA) diagnosis, digital NA detection (dNAD) as a single-molecular-level detection is greatly attributed to the perfect combination of NA amplification and microfluidic LOC techniques. In this chapter, the principle, classification, advances, and application of dNAD will be involved. In particular, the focus will be on chip-based dNAD for giving a deep interpretation of the analysis and evaluation of digital detection. The future prospect of dNAD is also anticipated. It is sure that dNAD by means of microfluidic LOC devices as the promising technique will better serve the ambitious plan of precision medicine through absolute quantitation of NA from individuals

Paper and Fiber-Based Bio-Diagnostic Platforms: Current Challenges and Future Needs

In this perspective article, some of the latest paper and fiber-based bio-analytical platforms are summarized, along with their fabrication strategies, the processing behind the product development, and the embedded systems in which paper or fiber materials were integrated. The article also reviews bio-recognition applications of paper/fiber-based devices, the detected analytes of interest, applied detection techniques, the related evaluation parameters, the type and duration of the assays, as well as the advantages and disadvantages of each technique. Moreover, some of the existing challenges of utilizing paper and/or fiber materials are discussed. These include control over the physical characteristics (porosity, permeability, wettability) and the chemical properties (surface functionality) of paper/fiber materials are discussed. Other aspects of the review focus on shelf life, the multi-functionality of the platforms, readout strategies, and other challenges that have to be addressed in order to obtain reliable detection outcomes. Keywords: paper-based bio-analytical devices; shelf life; equipment-free bio-recognition; flow rate; readout strategies; multi-functional platform

Micro/nanofluidic and lab-on-a-chip devices for biomedical applications

Micro/Nanofluidic and lab-on-a-chip devices have been increasingly used in biomedical research [1]. Because of their adaptability, feasibility, and cost-efficiency, these devices can revolutionize the future of preclinical technologies. Furthermore, they allow insights into the performance and toxic effects of responsive drug delivery nanocarriers to be obtained, which consequently allow the shortcomings of two/three-dimensional static cultures and animal testing to be overcome and help to reduce drug development costs and time [2–4]. With the constant advancements in biomedical technology, the development of enhanced microfluidic devices has accelerated, and numerous models have been reported. Given the multidisciplinary of this Special Issue (SI), papers on different subjects were published making a total of 14 contributions, 10 original research papers, and 4 review papers. The review paper of Ko et al. [1] provides a comprehensive overview of the significant advancements in engineered organ-on-a-chip research in a general way while in the review presented by Kanabekova and colleagues [2], a thorough analysis of microphysiological platforms used for modeling liver diseases can be found. To get a summary of the numerical models of microfluidic organ-on-a-chip devices developed in recent years, the review presented by Carvalho et al. [5] can be read. On the other hand, Maia et al. [6] report a systematic review of the diagnosis methods developed for COVID-19, providing an overview of the advancements made since the start of the pandemic. In the following, a brief summary of the research papers published in this SI will be presented, with organs-on-a-chip, microfluidic devices for detection, and device optimization having been identified as the main topics.info:eu-repo/semantics/publishedVersio