Publications by authors named "Zachary P Smith"

12 Publications

  • Page 1 of 1

Leveraging Free Volume Manipulation to Improve the Membrane Separation Performance of Amine-Functionalized PIM-1.

Angew Chem Int Ed Engl 2021 Mar 12;60(12):6593-6599. Epub 2021 Feb 12.

Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139, USA.

Gas-separation polymer membranes display a characteristic permeability-selectivity trade-off that has limited their industrial use. The most comprehensive approach to improving performance is to devise strategies that simultaneously increase fractional free volume, narrow free volume distribution, and enhance sorption selectivity, but generalizable methods for such approaches are exceedingly rare. Here, we present an in situ crosslinking and solid-state deprotection method to access previously inaccessible sorption and diffusion characteristics in amine-functionalized polymers of intrinsic microporosity. Free volume element (FVE) size can be increased while preserving a narrow FVE distribution, enabling below-upper bound polymers to surpass the H /N , H /CH , and O /N upper bounds and improving CO -based selectivities by 200 %. This approach can transform polymers into chemical analogues with improved performance, thereby overcoming traditional permeability-selectivity trade-offs.
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http://dx.doi.org/10.1002/anie.202012441DOI Listing
March 2021

Tuning Selectivities in Gas Separation Membranes Based on Polymer-Grafted Nanoparticles.

ACS Nano 2020 Nov 20. Epub 2020 Nov 20.

Department of Chemical Engineering, Columbia University, New York, New York 10027, United States.

Polymer membranes are critical to many sustainability applications that require the size-based separation of gas mixtures. Despite their ubiquity, there is a continuing need to selectively affect the transport of different mixture components while enhancing mechanical strength and hindering aging. Polymer-grafted nanoparticles (GNPs) have recently been explored in the context of gas separations. Membranes made from pure GNPs have higher gas permeability and lower selectivity relative to the neat polymer because they have increased mean free volume. Going beyond this ability to manipulate the mean free volume by grafting chains to a nanoparticle, the conceptual advance of the present work is our finding that GNPs are spatially heterogeneous transport media, with this free volume distribution being easily manipulated by the addition of free polymer. In particular, adding a small amount of appropriately chosen free polymer can increase the membrane gas selectivity by up to two orders of magnitude while only moderately reducing small gas permeability. Added short free chains, which are homogeneously distributed in the polymer layer of the GNP, reduce the permeability of all gases but yield no dramatic increases in selectivity. In contrast, free chains with length comparable to the grafts, which populate the interstitial pockets between GNPs, preferentially hinder the transport of the larger gas and thus result in large selectivity increases. This work thus establishes that we can favorably manipulate the selective gas transport properties of GNP membranes through the entropic effects associated with the addition of free chains.
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http://dx.doi.org/10.1021/acsnano.0c07049DOI Listing
November 2020

The disutility of stress testing in low-risk HEART Pathway patients.

Am J Emerg Med 2020 Aug 15. Epub 2020 Aug 15.

Department of Emergency Medicine, Wake Forest School of Medicine, Winston Salem, NC, United States.

Background: The HEART Pathway identifies low-risk chest pain patients for discharge from the Emergency Department without stress testing. However, HEART Pathway recommendations are not always followed. The objective of this study is to determine the frequency and diagnostic yield of stress testing among low-risk patients.

Methods: An academic hospital's chest pain registry was analyzed for low-risk HEART Pathway patients (HEAR score ≤ 3 with non-elevated troponins) from 1/2017 to 7/2018. Stress tests were reviewed for inducible ischemia. Diagnostic yield was defined as the rate of obstructive CAD among patients with positive stress testing. T-test or Fisher's exact test was used to test the univariate association of age, sex, race/ethnicity, and HEAR score with stress testing. Multivariate logistic regression was used to determine the association of age, sex, race/ethnicity, and HEAR score with stress testing.

Results: There were 4743 HEART Pathway assessments, with 43.7% (2074/4743) being low-risk. Stress testing was performed on 4.1% (84/2074). Of the 84 low-risk patients who underwent testing, 8.3% (7/84) had non-diagnostic studies and 2.6% (2/84) had positive studies. Among the 2 patients with positive studies, angiography revealed that 1 had widely patent coronary arteries and the other had multivessel obstructive coronary artery disease, making the diagnostic yield of stress testing 1.2% (1/84). Each one-point increase in HEAR score (aOR 2.17, 95% CI 1.45-3.24) and being male (aOR 1.59, 95% CI 1.02-2.49) were associated with testing.

Conclusions: Stress testing among low-risk HEART Pathway patients was uncommon, low yield, and more likely in males and those with a higher HEAR score.
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http://dx.doi.org/10.1016/j.ajem.2020.08.032DOI Listing
August 2020

MOF-Based Membranes for Gas Separations.

Chem Rev 2020 Aug 1;120(16):8161-8266. Epub 2020 Jul 1.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

Metal-organic frameworks (MOFs) represent the largest known class of porous crystalline materials ever synthesized. Their narrow pore windows and nearly unlimited structural and chemical features have made these materials of significant interest for membrane-based gas separations. In this comprehensive review, we discuss opportunities and challenges related to the formation of pure MOF films and mixed-matrix membranes (MMMs). Common and emerging separation applications are identified, and membrane transport theory for MOFs is described and contextualized relative to the governing principles that describe transport in polymers. Additionally, cross-cutting research opportunities using advanced metrologies and computational techniques are reviewed. To quantify membrane performance, we introduce a simple membrane performance score that has been tabulated for all of the literature data compiled in this review. These data are reported on upper bound plots, revealing classes of MOF materials that consistently demonstrate promising separation performance. Recommendations are provided with the intent of identifying the most promising materials and directions for the field in terms of fundamental science and eventual deployment of MOF materials for commercial membrane-based gas separations.
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http://dx.doi.org/10.1021/acs.chemrev.0c00119DOI Listing
August 2020

Quantifying Patient Subpopulation Disparities in New Drugs and Biologics Approved Between 2007 and 2017.

Ther Innov Regul Sci 2020 11 18;54(6):1541-1550. Epub 2020 Jun 18.

Tufts Center for the Study of Drug Development, Tufts University School of Medicine, Boston, MA, USA.

Background: Tufts CSDD conducted a study to quantify the magnitude of participant subgroup demographic disparities in industry-funded pivotal trials and establish baseline participant diversity measures.

Methods: Eleven years of data on pivotal trials of all novel drugs and biologics approved between 2007 and 2017 (n = 341 drugs and n = 757 pivotal trials) was compiled and analyzed.

Results: The availability of reported participant demographic subgroup data was poor-most notably participant ethnicity with 63% of pivotal trials supporting all approved treatments missing data. The availability of data on participant race and ethnicity did not improve between 2007 and 2017. Participants of Black or of African Descent were the subgroup most highly under-represented. Three times as many participants in this demographic subgroup should have been enrolled in pivotal trials to achieve representation as dictated by disease prevalence rates and population census figures. Although variation was observed between disease conditions, under-representation of Black/African Descent participants occurred in nearly all conditions. Participants from indigenous communities were also highly under-represented. Asian participants were highly over-represented in pivotal trials. Approximately 14% more Hispanic/Latinx participants should have been enrolled in clinical trials to achieve population-proportional representation.

Conclusions: The results suggest that participant demographic disclosure practices are falling short and that insufficient diversity in clinical trials is limiting the value of guidance on medical treatment dosing and response. The study findings supplement the FDA's Drug Trial Snapshot Reports and offer insight into the magnitude of, and trends in, participant demographic subgroup disparities.
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http://dx.doi.org/10.1007/s43441-020-00181-9DOI Listing
November 2020

Mixed-Matrix Membranes Formed from Imide-Functionalized UiO-66-NH for Improved Interfacial Compatibility.

ACS Appl Mater Interfaces 2019 Aug 14;11(34):31257-31269. Epub 2019 Aug 14.

Department of Chemical Engineering , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.

Mixed-matrix membranes (MMMs) formed by dispersing metal-organic framework (MOF) particles in polymers have attracted significant attention because these composite systems can potentially surpass the separation performance of pure polymers alone. However, performance improvements are often unrealized because of poor interfacial compatibility between the MOF and the polymer, which results in interfacial defects. From a practical perspective, strategies are needed to address these defects so that MMMs can be deployed in real-world separation processes. From a fundamental perspective, strategies are needed to reliably form defect-free MMMs so that transport models can be applied to estimate pure MOF property sets, thereby enabling the development of robust structure-property relationships. To address these interfacial challenges, we have developed a method to surface-functionalize a UiO-66-NH MOF with a nanoscopic shell of covalently tethered 4,4'-(hexafluoroisopropylidene)diphthalic anhydride-Durene oligomers. When combined with a high-molecular-weight polymer of identical chemical structure to that of the imide-functional MOF surface, defect-free MMMs with uniform particle dispersions can be formed. With this technique, both permeabilities and selectivities of select gases in the MMMs were improved at loadings ranging from 5 to 40 wt %. At a 40 wt % loading, CO permeability and CO/CH selectivity were enhanced by 48 and 15%, respectively. Additionally, pure MOF permeabilities for H, N, O, CH, and CO were predicted by the Maxwell model.
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http://dx.doi.org/10.1021/acsami.9b07500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727620PMC
August 2019

Polymers with Side Chain Porosity for Ultrapermeable and Plasticization Resistant Materials for Gas Separations.

Adv Mater 2019 May 9;31(21):e1807871. Epub 2019 Apr 9.

Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Polymer membranes with ultrahigh CO permeabilities and high selectivities are needed to address some of the critical separation challenges related to energy and the environment, especially in natural gas purification and postcombustion carbon capture. However, very few solution-processable, linear polymers are known today that access these types of characteristics, and all of the known structures achieve their separation performance through the design of rigid backbone chemistries that concomitantly increase chain stiffness and interchain spacing, thereby resulting in ultramicroporosity in solid-state chain-entangled films. Herein, the separation performance of a porous polymer obtained via ring-opening metathesis polymerization is reported, which possesses a flexible backbone with rigid, fluorinated side chains. This polymer exhibits ultrahigh CO permeability (>21 000 Barrer) and exceptional plasticization resistance (CO plasticization pressure > 51 bar). Compared to traditional polymers of intrinsic microporosity, the rate of physical aging is slower, especially for gases with small effective diameters (i.e., He, H , and O ). This structural design strategy, coupled with studies on fluorination, demonstrates a generalizable approach to create new polymers with flexible backbones and pore-forming side chains that have unexplored promise for small-molecule separations.
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http://dx.doi.org/10.1002/adma.201807871DOI Listing
May 2019

Mixed-Matrix Membranes Formed from Multi-Dimensional Metal-Organic Frameworks for Enhanced Gas Transport and Plasticization Resistance.

ChemSusChem 2019 Jun 29;12(11):2355-2360. Epub 2019 Apr 29.

Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts, 02139, USA.

Mixed-matrix membranes (MMMs) formed by incorporating metal-organic frameworks (MOFs) into polymers have a general limitation in that the MOFs are typically formed into rather simple dimensionalities (such as 1D, 2D, or 3D). Each design approach has intrinsic-albeit independent-benefits, such as network percolation (1D), access to high-aspect ratios (2D), and ease of processability (3D). However, a design strategy is needed to combine multiple dimensionalities and, thereby, access the full range of transport and compositing benefits of these high-performance materials. Herein, a facile method to form multi-dimensional HKUST-1 nanoparticles is introduced by using a modulator to tune the MOF nucleation and growth mechanism. At 30 wt % multidimensional MOF loading, the MMM shows CO permeabilities of approximately 2500 Barrer, which represents a 2.5-fold increase compared to that of a pure polymer without a large loss of selectivity for CO /CH and CO /N . Additionally, almost no plasticization pressure response is observed for CO up to 750 psi, suggesting an unusual stability to high activity feeds.
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http://dx.doi.org/10.1002/cssc.201900623DOI Listing
June 2019

Engineered Transport in Microporous Materials and Membranes for Clean Energy Technologies.

Adv Mater 2018 Feb 8;30(8). Epub 2018 Jan 8.

Materials Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Rd, Berkeley, CA, 94720, USA.

Many forward-looking clean-energy technologies hinge on the development of scalable and efficient membrane-based separations. Ongoing investment in the basic research of microporous materials is beginning to pay dividends in membrane technology maturation. Specifically, improvements in membrane selectivity, permeability, and durability are being leveraged for more efficient carbon capture, desalination, and energy storage, and the market adoption of membranes in those areas appears to be on the horizon. Herein, an overview of the microporous materials chemistry driving advanced membrane development, the clean-energy separations employing them, and the theoretical underpinnings tying membrane performance to membrane structure across multiple length scales is provided. The interplay of pore architecture and chemistry for a given set of analytes emerges as a critical design consideration dictating mass transport outcomes. Opportunities and outstanding challenges in the field are also discussed, including high-flux 2D molecular-sieving membranes, phase-change adsorbents as performance-enhancing components in composite membranes, and the need for quantitative metrologies for understanding mass transport in heterophasic materials and in micropores with unusual chemical interactions with analytes of interest.
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http://dx.doi.org/10.1002/adma.201704953DOI Listing
February 2018

Enhanced ethylene separation and plasticization resistance in polymer membranes incorporating metal-organic framework nanocrystals.

Nat Mater 2016 08 11;15(8):845-9. Epub 2016 Apr 11.

Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California 94720, USA.

The implementation of membrane-based separations in the petrochemical industry has the potential to reduce energy consumption significantly relative to conventional separation processes. Achieving this goal, however, requires the development of new membrane materials with greater selectivity, permeability and stability than available at present. Here, we report composite materials consisting of nanocrystals of metal-organic frameworks dispersed within a high-performance polyimide, which can exhibit enhanced selectivity for ethylene over ethane, greater ethylene permeability and improved membrane stability. Our results suggest that framework-polymer interactions reduce chain mobility of the polymer while simultaneously boosting membrane separation performance. The increased stability, or plasticization resistance, is expected to improve membrane utility under real process conditions for petrochemical separations and natural gas purification. Furthermore, this approach can be broadly applied to numerous polymers that encounter aggressive environments, potentially making gas separations possible that were previously inaccessible to membranes.
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http://dx.doi.org/10.1038/nmat4621DOI Listing
August 2016

Graphene oxide: a new platform for high-performance gas- and liquid-separation membranes.

Angew Chem Int Ed Engl 2014 Sep 22;53(39):10286-8. Epub 2014 Jul 22.

Department of Chemical Engineering, Texas Materials Institute, and Center for Energy and Environmental Resources, The University of Texas at Austin, 10100 Burnet Road, Bldg. 133, Austin, TX 78758 (USA) http://membrane.ces.utexas.edu.

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http://dx.doi.org/10.1002/anie.201404407DOI Listing
September 2014

Growth of human pancreatic cancer is inhibited by down-regulation of gastrin gene expression.

Pancreas 2009 Jul;38(5):e151-61

Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17011, USA.

Objectives: This study evaluated the effects of gastrin messenger RNA (mRNA) down-regulation on growth of human pancreatic cancer.

Methods: Gastrin expression was examined in human pancreatic cancer cell lines by reverse transcriptase-polymerase chain reaction, and peptide expression was assessed by immunocytochemistry. Gastrin was down-regulated using either stable transfection of an antisense gastrin cDNA or 1 of 3 shRNA (short hairpin RNA) constructs. Tumor formation was evaluated after either subcutaneous or orthotopic injections into nude mice. The effect of nanoliposomes loaded with gastrin siRNA (small interfering RNA) was tested in mice bearing pancreatic tumors.

Results: Stable transfection of gastrin antisense or shRNAs into BxPC-3 cells resulted in clones with more than 90% reduction in gastrin mRNA. Tumor growth rate and incidence of metastases in both wild-type and transfected pancreatic cancer cells were directly proportional to the degrees of gastrin mRNA expression. Immunofluorescence analysis confirmed that gastrin peptide levels were decreased in antisense and shRNA tumors. Gastrin knockdown clones had lower Ki-67 and increased cleaved caspase-3 staining, consistent with known effects of gastrin on proliferation and apoptosis. Tumors in mice treated with gastrin siRNA were smaller than controls.

Conclusions: These results suggest that RNAi targeting of gastrin could serve as an effective treatment for pancreatic cancer.
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http://dx.doi.org/10.1097/MPA.0b013e3181a66fdcDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704379PMC
July 2009