TECHNOLOGY Pub Date : 2020-03-01 Epub Date: 2020-11-05 DOI: 10.1142/s2339547820500028

Omar Haque, Casie A Pendexter, Stephanie E J Cronin, Siavash Raigani, Reiner J de Vries, Heidi Yeh, James F Markmann, Korkut Uygun

{"title":"Twenty-four hour ex-vivo normothermic machine perfusion in rat livers.","authors":"Omar Haque, Casie A Pendexter, Stephanie E J Cronin, Siavash Raigani, Reiner J de Vries, Heidi Yeh, James F Markmann, Korkut Uygun","doi":"10.1142/s2339547820500028","DOIUrl":"10.1142/s2339547820500028","url":null,"abstract":"Ex-vivo liver perfusion (EVLP) is an ideal platform to study liver disease, therapeutic interventions, and pharmacokinetic properties of drugs without any patient risk. Rat livers are an ideal model for EVLP due to less organ quality variability, ease of hepatectomy, well-defined molecular pathways, and relatively low costs compared to large animal or human perfusions. However, the major limitation with rat liver normothermic machine perfusion (NMP) is maintaining physiologic liver function on an ex-vivo machine perfusion system. To address this need, our research demonstrates 24-hour EVLP in rats under normothermic conditions. Early (6 hour) perfusate transaminase levels and oxygen consumption of the liver graft are shown to be good markers of perfusion success and correlate with viable 24-hour post-perfusion histology. Finally, we address overcoming challenges in long-term rat liver perfusions such as rising intrahepatic pressures and contamination, and offer future directions necessary to build upon our work.","PeriodicalId":22332,"journal":{"name":"TECHNOLOGY","volume":"8 1-2","pages":"27-36"},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300916/pdf/nihms-1646032.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39225465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

First-in-human evaluation of a hand-held automated venipuncture device for rapid venous blood draws. 首次对用于快速静脉抽血的手持式自动静脉穿刺装置进行人体评估。

TECHNOLOGY Pub Date : 2019-09-01 Epub Date: 2020-01-22 DOI: 10.1142/S2339547819500067

Josh M Leipheimer, Max L Balter, Alvin I Chen, Enrique J Pantin, Alexander E Davidovich, Kristen S Labazzo, Martin L Yarmush

{"title":"First-in-human evaluation of a hand-held automated venipuncture device for rapid venous blood draws.","authors":"Josh M Leipheimer, Max L Balter, Alvin I Chen, Enrique J Pantin, Alexander E Davidovich, Kristen S Labazzo, Martin L Yarmush","doi":"10.1142/S2339547819500067","DOIUrl":"10.1142/S2339547819500067","url":null,"abstract":"Obtaining venous access for blood sampling or intravenous (IV) fluid delivery is an essential first step in patient care. However, success rates rely heavily on clinician experience and patient physiology. Difficulties in obtaining venous access result in missed sticks and injury to patients, and typically require alternative access pathways and additional personnel that lengthen procedure times, thereby creating unnecessary costs to healthcare facilities. Here, we present the first-in-human assessment of an automated robotic venipuncture device designed to safely perform blood draws on peripheral forearm veins. The device combines ultrasound imaging and miniaturized robotics to identify suitable vessels for cannulation and robotically guide an attached needle toward the lumen center. The device demonstrated results comparable to or exceeding that of clinical standards, with a success rate of 87% on all participants (n = 31), a 97% success rate on nondifficult venous access participants (n = 25), and an average procedure time of 93 ± 30 s (n = 31). In the future, this device can be extended to other areas of vascular access such as IV catheterization, central venous access, dialysis, and arterial line placement.","PeriodicalId":22332,"journal":{"name":"TECHNOLOGY","volume":"7 3-4","pages":"98-107"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156113/pdf/nihms-1555677.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37837582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A protein interaction free energy model based on amino acid residue contributions: Assessment of point mutation stability of T4 lysozyme. 基于氨基酸残基贡献的蛋白质相互作用自由能模型：T4溶菌酶点突变稳定性的评估。

TECHNOLOGY Pub Date : 2019-03-01 Epub Date: 2019-04-26 DOI: 10.1142/s233954781950002x

Lawrence J Williams, Brian J Schendt, Zachary R Fritz, Yonatan Attali, Robert H Lavroff, Martin L Yarmush

{"title":"A protein interaction free energy model based on amino acid residue contributions: Assessment of point mutation stability of T4 lysozyme.","authors":"Lawrence J Williams, Brian J Schendt, Zachary R Fritz, Yonatan Attali, Robert H Lavroff, Martin L Yarmush","doi":"10.1142/s233954781950002x","DOIUrl":"10.1142/s233954781950002x","url":null,"abstract":"Here we present a model to estimate the interaction free energy contribution of each amino acid residue of a given protein. Protein interaction energy is described in terms of per-residue interaction factors, μ. Multibody interactions are implicitly captured in μ through the combination of amino acid terms (γ) guided by local conformation indices (σ). The model enables construction of an interaction factor heat map for a protein in a given fold, allows prima facie assessment of the degree of residue-residue interaction, and facilitates a qualitative and quantitative evaluation of protein association properties. The model was used to compute thermal stability of T4 bacteriophage lysozyme mutants across seven sites. Qualitative assessment of mutational effects provides a straightforward rationale regarding whether a particular site primarily perturbs native or non-native states, or both. The presented model was found to be in good agreement with experimental mutational data (R 2 = 0.73) and suggests an approach by which to convert structure space into energy space.","PeriodicalId":22332,"journal":{"name":"TECHNOLOGY","volume":"7 1-2","pages":"12-39"},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/s233954781950002x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37770243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

The growing role of precision and personalized medicine for cancer treatment. 精准和个性化药物在癌症治疗中的作用越来越大。

TECHNOLOGY Pub Date : 2018-09-01 Epub Date: 2019-01-11 DOI: 10.1142/S2339547818300020

Paulina Krzyszczyk, Alison Acevedo, Erika J Davidoff, Lauren M Timmins, Ileana Marrero-Berrios, Misaal Patel, Corina White, Christopher Lowe, Joseph J Sherba, Clara Hartmanshenn, Kate M O'Neill, Max L Balter, Zachary R Fritz, Ioannis P Androulakis, Rene S Schloss, Martin L Yarmush

{"title":"The growing role of precision and personalized medicine for cancer treatment.","authors":"Paulina Krzyszczyk, Alison Acevedo, Erika J Davidoff, Lauren M Timmins, Ileana Marrero-Berrios, Misaal Patel, Corina White, Christopher Lowe, Joseph J Sherba, Clara Hartmanshenn, Kate M O'Neill, Max L Balter, Zachary R Fritz, Ioannis P Androulakis, Rene S Schloss, Martin L Yarmush","doi":"10.1142/S2339547818300020","DOIUrl":"10.1142/S2339547818300020","url":null,"abstract":"Cancer is a devastating disease that takes the lives of hundreds of thousands of people every year. Due to disease heterogeneity, standard treatments, such as chemotherapy or radiation, are effective in only a subset of the patient population. Tumors can have different underlying genetic causes and may express different proteins in one patient versus another. This inherent variability of cancer lends itself to the growing field of precision and personalized medicine (PPM). There are many ongoing efforts to acquire PPM data in order to characterize molecular differences between tumors. Some PPM products are already available to link these differences to an effective drug. It is clear that PPM cancer treatments can result in immense patient benefits, and companies and regulatory agencies have begun to recognize this. However, broader changes to the healthcare and insurance systems must be addressed if PPM is to become part of standard cancer care.","PeriodicalId":22332,"journal":{"name":"TECHNOLOGY","volume":"6 3-4","pages":"79-100"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36972355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tri-culture system for pro-hapten sensitizer identification and potency classification. 半抗原前致敏剂鉴定及效价分类的三培养体系。

TECHNOLOGY Pub Date : 2018-06-01 Epub Date: 2018-06-29 DOI: 10.1142/S233954781850005X

Serom Lee, Talia Greenstein, Lingting Shi, Tim Maguire, Rene Schloss, Martin Yarmush

{"title":"Tri-culture system for pro-hapten sensitizer identification and potency classification.","authors":"Serom Lee, Talia Greenstein, Lingting Shi, Tim Maguire, Rene Schloss, Martin Yarmush","doi":"10.1142/S233954781850005X","DOIUrl":"https://doi.org/10.1142/S233954781850005X","url":null,"abstract":"Allergic contact dermatitis (ACD) is an inflammatory disease that impacts 15-20% of the general population and accurate screening methods for chemical risk assessment are needed. However, most approaches poorly predict pre- and pro-hapten sensitizers, which require abiotic or metabolic conversion prior to inducing sensitization. We developed a tri-culture system comprised of MUTZ-3-derived Langerhans cells, HaCaT keratinocytes, and primary dermal fibroblasts to mimic the cellular and metabolic environments of skin sensitization. A panel of non-sensitizers and sensitizers was tested and the secretome was evaluated. A support vector machine (SVM) was used to identify the most predictive sensitization signature and classification trees identified statistical thresholds to predict sensitizer potency. The SVM computed 91% tri-culture prediction accuracy using the top 3 ranking biomarkers (IL-8, MIP-1β, and GM-CSF) and improved the detection of pre- and pro-haptens. This in vitro assay combined with in silico data analysis presents a promising approach and offers the possibility of multi-metric analysis for enhanced ACD sensitizer screening.","PeriodicalId":22332,"journal":{"name":"TECHNOLOGY","volume":"6 2","pages":"67-74"},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S233954781850005X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36800760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Automated end-to-end blood testing at the point-of-care: Integration of robotic phlebotomy with downstream sample processing. 护理点自动化端到端血液检测：将机器人静脉切开术与下游样本处理集成。

TECHNOLOGY Pub Date : 2018-06-01 DOI: 10.1142/S2339547818500048

M L Balter, J M Leipheimer, A I Chen, A Shrirao, T J Maguire, M L Yarmush

{"title":"Automated end-to-end blood testing at the point-of-care: Integration of robotic phlebotomy with downstream sample processing.","authors":"M L Balter, J M Leipheimer, A I Chen, A Shrirao, T J Maguire, M L Yarmush","doi":"10.1142/S2339547818500048","DOIUrl":"10.1142/S2339547818500048","url":null,"abstract":"Diagnostic blood testing is the most commonly performed clinical procedure in the world, and influences the majority of medical decisions made in hospital and laboratory settings. However, manual blood draw success rates are dependent on clinician skill and patient physiology, and results are generated almost exclusively in centralized labs from large-volume samples using labor-intensive analytical techniques. This paper presents a medical device that enables end-to-end blood testing by performing blood draws and providing diagnostic results in a fully automated fashion at the point-of-care. The system couples an image-guided venipuncture robot, developed to address the challenges of routine venous access, with a centrifuge-based blood analyzer to obtain quantitative measurements of hematology. We first demonstrate a white blood cell assay on the analyzer, using a blood mimicking fluid spiked with fluorescent microbeads, where the area of the packed bead layer is correlated with the bead concentration. Next we perform experiments to evaluate the pumping efficiency of the sample handling module. Finally, studies are conducted on the integrated device - from blood draw to analysis - using blood vessel phantoms to assess the accuracy and repeatability of the resulting white blood cell assay.","PeriodicalId":22332,"journal":{"name":"TECHNOLOGY","volume":"6 2","pages":"59-66"},"PeriodicalIF":0.0,"publicationDate":"2018-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058193/pdf/nihms-981354.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36352039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microfluidic flow cytometry: The role of microfabrication methodologies, performance and functional specification. 微流体流式细胞仪：微制造方法、性能和功能规范的作用。

TECHNOLOGY Pub Date : 2018-03-01 Epub Date: 2018-03-16 DOI: 10.1142/S2339547818300019

Anil B Shrirao, Zachary Fritz, Eric M Novik, Gabriel M Yarmush, Rene S Schloss, Jeffrey D Zahn, Martin L Yarmush

{"title":"Microfluidic flow cytometry: The role of microfabrication methodologies, performance and functional specification.","authors":"Anil B Shrirao, Zachary Fritz, Eric M Novik, Gabriel M Yarmush, Rene S Schloss, Jeffrey D Zahn, Martin L Yarmush","doi":"10.1142/S2339547818300019","DOIUrl":"10.1142/S2339547818300019","url":null,"abstract":"Flow cytometry is an invaluable tool utilized in modern biomedical research and clinical applications requiring high throughput, high resolution particle analysis for cytometric characterization and/or sorting of cells and particles as well as for analyzing results from immunocytometric assays. In recent years, research has focused on developing microfluidic flow cytometers with the motivation of creating smaller, less expensive, simpler, and more autonomous alternatives to conventional flow cytometers. These devices could ideally be highly portable, easy to operate without extensive user training, and utilized for research purposes and/or point-of-care diagnostics especially in limited resource facilities or locations requiring on-site analyses. However, designing a device that fulfills the criteria of high throughput analysis, automation and portability, while not sacrificing performance is not a trivial matter. This review intends to present the current state of the field and provide considerations for further improvement by focusing on the key design components of microfluidic flow cytometers. The recent innovations in particle focusing and detection strategies are detailed and compared. This review outlines performance matrix parameters of flow cytometers that are interdependent with each other, suggesting trade offs in selection based on the requirements of the applications. The ongoing contribution of microfluidics demonstrates that it is a viable technology to advance the current state of flow cytometry and develop automated, easy to operate and cost-effective flow cytometers.","PeriodicalId":22332,"journal":{"name":"TECHNOLOGY","volume":"6 1","pages":"1-23"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907470/pdf/nihms957841.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36032555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel model for ex situ reperfusion of the human liver following subnormothermic machine perfusion. 一种新型的人肝脏离体再灌注模型。

TECHNOLOGY Pub Date : 2017-12-01 Epub Date: 2017-11-10 DOI: 10.1142/S2339547817500108

James H Avruch, Bote G Bruinsma, Pepijn D Weeder, Gautham V Sridharan, Robert J Porte, Heidi Yeh, James F Markmann, Korkut Uygun

{"title":"A novel model for ex situ reperfusion of the human liver following subnormothermic machine perfusion.","authors":"James H Avruch, Bote G Bruinsma, Pepijn D Weeder, Gautham V Sridharan, Robert J Porte, Heidi Yeh, James F Markmann, Korkut Uygun","doi":"10.1142/S2339547817500108","DOIUrl":"https://doi.org/10.1142/S2339547817500108","url":null,"abstract":"Machine perfusion-based organ preservation techniques are prudently transitioning into clinical practice. Although experimental data is compelling, the outcomes in the highly variable clinical donation-transplantation setting are unpredictable. Here, we offer an intermediate tool for pre-clinical assessment of human donor livers. We present a model for ex situ reperfusion of discarded human livers and report on its application in three human livers that have undergone subnormothermic (21°C) machine perfusion as an experimental preservation method. During reperfusion, the livers macroscopically reperfused in the first 15 minutes, and remained visually well-perfused for 3 hours of ex situ reperfusion. Bile production and oxygen consumption were observed throughout ex situ reperfusion. ATP levels increased 4.25-fold during SNMP. Between the end of SNMP and the end of reperfusion ATP levels dropped 45%. ALT levels in blood increased rapidly in the first 30 minutes and ALT release continued to taper off towards the end of perfusion. Release of CRP, TNF-α, IL-1β, and IL-12, IFN-γ was sustained during reperfusion. These findings support the use of this model for the evaluation of novel human liver preservation techniques.","PeriodicalId":22332,"journal":{"name":"TECHNOLOGY","volume":"5 4","pages":"196-200"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1142/S2339547817500108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37255014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

A thermoreversible, photocrosslinkable collagen bio-ink for free-form fabrication of scaffolds for regenerative medicine. 一种热可逆、光交联胶原生物墨水，可用于再生医学支架的自由形态制造。

TECHNOLOGY Pub Date : 2017-12-01 Epub Date: 2017-10-17 DOI: 10.1142/S2339547817500091

Kathryn E Drzewiecki, Juilee N Malavade, Ijaz Ahmed, Christopher J Lowe, David I Shreiber

{"title":"A thermoreversible, photocrosslinkable collagen bio-ink for free-form fabrication of scaffolds for regenerative medicine.","authors":"Kathryn E Drzewiecki, Juilee N Malavade, Ijaz Ahmed, Christopher J Lowe, David I Shreiber","doi":"10.1142/S2339547817500091","DOIUrl":"10.1142/S2339547817500091","url":null,"abstract":"As a biomaterial, collagen has been used throughout tissue engineering and regenerative medicine. Collagen is native to the body, is highly biocompatible, and naturally promotes cell adhesion and regeneration. However, collagen fibers and the inherent weak mechanical properties of collagen hydrogels interfere with further development of collagen as a bio-ink. Herein, we demonstrate the use of a modified type-I collagen, collagen methacrylamide (CMA), as a fibril-forming bio-ink for free-form fabrication of scaffolds. Like collagen, CMA can self-assemble into a fibrillar hydrogel at physiological conditions. In contrast, CMA is photocrosslinkable and thermoreversible, and photocrosslinking eliminates thermoreversibility. Free-form fabrication of CMA was performed through self-assembly of the CMA hydrogel, photocrosslinking the structure of interest using a photomask, and cooling the entire hydrogel, which results in cold-melting of unphotocrosslinked regions. Printed hydrogels had a resolution on the order of ~350 μm, and can be fabricated with or without cells and maintain viability or be further processed into freeze-dried sponges, all while retaining pattern fidelity. A subcutaneous implant study confirmed the biocompatibility of CMA in comparison to collagen. Free-form fabrication of CMA allows for printing of macroscale, customized scaffolds with good pattern fidelity and can be implemented with relative ease for continued research and development of collagen-based scaffolds in tissue engineering.","PeriodicalId":22332,"journal":{"name":"TECHNOLOGY","volume":"5 4","pages":"185-195"},"PeriodicalIF":0.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845803/pdf/nihms942882.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35915670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell-sized lipid vesicles for cell-cell synaptic therapies. 细胞大小的脂质囊泡用于细胞-细胞突触疗法。

TECHNOLOGY Pub Date : 2017-12-01 Epub Date: 2018-01-24 DOI: 10.1142/S233954781750011X

D Vallejo, S H Lee, D Lee, C Zhang, C Rapier, S D Chessler, A P Lee

引用次数: 0

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