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Article ; Online: Monitoring and modulation of the tumor microenvironment for enhanced cancer modeling.

Head, Tristen / Cady, Nathaniel C

Experimental biology and medicine (Maywood, N.J.)

2022 Volume 247, Issue 7, Page(s) 598–613

Abstract: Cancer treatments utilizing biologic or cytotoxic drugs compose the frontline of therapy, and though gains in treatment efficacy have been persistent in recent decades, much work remains in understanding cancer progression and treatment. Compounding this ...

Abstract	Cancer treatments utilizing biologic or cytotoxic drugs compose the frontline of therapy, and though gains in treatment efficacy have been persistent in recent decades, much work remains in understanding cancer progression and treatment. Compounding this situation is the low rate of success when translating preclinical drug candidates to the clinic, which raises costs and development timelines. This underperformance is due in part to the poor recapitulation of the tumor microenvironment, a critical component of cancer biology, in cancer model systems. New technologies capable of both accurately observing and manipulating the tumor microenvironment are needed to effectively model cancer response to treatment. In this review, conventional cancer models are summarized, and a primer on emerging techniques for monitoring and modulating the tumor microenvironment is presented and discussed.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Humans ; Neoplasms/drug therapy ; Neoplasms/pathology ; Tumor Microenvironment
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2022-01-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1177/15353702221074293
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Article ; Online: Surveilling cellular vital signs: toward label-free biosensors and real-time viability assays for bioprocessing.

Rosenberg, Julian N / Cady, Nathaniel C

Current opinion in biotechnology

2021 Volume 71, Page(s) 123–129

Abstract: Cell viability is an essential facet of mammalian and microbial bioprocessing. While robust methods of monitoring cellular health remain critically important to biomanufacturing and biofabrication, the complexity of advanced cell culture platforms often ... ...

Abstract	Cell viability is an essential facet of mammalian and microbial bioprocessing. While robust methods of monitoring cellular health remain critically important to biomanufacturing and biofabrication, the complexity of advanced cell culture platforms often poses challenges for conventional viability assays. This review surveys novel approaches to discern the metabolic, morphological, and mechanistic hallmarks of living systems - spanning subcellular and multicellular scales. While fluorescent probes coupled with 3D image analysis generate rapid results with spatiotemporal detail, molecular techniques like viability PCR can distinguish live cells with genetic specificity. Notably, label-free biosensors can detect nuanced attributes of cellular vital signs with single-cell resolution via optical, acoustic, and electrical signals. Ultimately, efforts to integrate these modalities with automation, machine learning, and high-throughput workflows will lead to exciting new vistas across the cell viability landscape.
MeSH term(s)	Animals ; Biological Assay ; Biosensing Techniques ; Cell Culture Techniques ; Cell Survival ; Vital Signs
Language	English
Publishing date	2021-08-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1052045-4
ISSN	1879-0429 ; 0958-1669
ISSN (online)	1879-0429
ISSN	0958-1669
DOI	10.1016/j.copbio.2021.07.004
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Article ; Online: Dual detection of COVID-19 antigens and antibodies using nanoscale fluorescent plasmonic substrates.

Taubner, Benjamin / Gibbons, Ashley / Cady, Nathaniel C

Experimental biology and medicine (Maywood, N.J.)

2022 Volume 247, Issue 23, Page(s) 2081–2089

Abstract: There is a continuing need for biosensors that can be used in the diagnosis of COVID-19 infection and to measure a subject's immune response to the virus itself (SARS-CoV-2). In this study, grating-coupled fluorescent plasmonic (GC-FP)-based detection of ...

Abstract	There is a continuing need for biosensors that can be used in the diagnosis of COVID-19 infection and to measure a subject's immune response to the virus itself (SARS-CoV-2). In this study, grating-coupled fluorescent plasmonic (GC-FP)-based detection of SARS-CoV-2 antigens was coupled with antibody detection to yield a dual-mode detection assay. Pairs of capture and detection antibodies were screened for direct detection of the SARS-CoV-2 nucleocapsid (Nuc) antigen, which were then combined with an existing GC-FP antibody detection assay. Nuc could be detected as low as 1 µg/mL concentrations, while antibodies were detectable to 50 ng/mL. The dual detection assay was tested by adding purified Nuc antigen to serum from a polymerase chain reaction (PCR)-positive COVID-19-infected individual. Using this sample, co-detection of Nuc antigen and anti-spike protein antibodies was successfully performed on a single GC-FP chip. Total assay time was 1 h, making this the first known example of rapid dual antibody and antigen detection on the same biosensor chip.
MeSH term(s)	Humans ; COVID-19/diagnosis ; SARS-CoV-2 ; Antibodies, Viral ; COVID-19 Testing ; Sensitivity and Specificity
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2022-08-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1177/15353702221113860
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Article ; Online: Quantitative multiplexed strategies for human Lyme disease serological testing.

Chou, Eunice / Minor, Armond / Cady, Nathaniel C

Experimental biology and medicine (Maywood, N.J.)

2021 Volume 246, Issue 12, Page(s) 1388–1399

Abstract: Lyme disease, which is primarily caused by infection with the ... ...

Abstract	Lyme disease, which is primarily caused by infection with the bacterium
MeSH term(s)	Antigens, Bacterial/immunology ; Borrelia burgdorferi/immunology ; Humans ; Immunity/immunology ; Lyme Disease/diagnosis ; Lyme Disease/immunology ; Sensitivity and Specificity ; Serologic Tests/methods
Chemical Substances	Antigens, Bacterial
Language	English
Publishing date	2021-04-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1177/15353702211003496
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Article: Lithographically patterned micro-nozzles for controlling fluid flow profiles for drug delivery and in vitro imaging applications.

Head, Tristen / Tokranova, Natalya / Cady, Nathaniel C

MRS communications

2021 Volume 11, Issue 5, Page(s) 584–589

Abstract: Precisely controlling delivery of drugs and other reagents is important for intravital microscopy studies. In this work, photolithographic integration of micro-nozzles onto a microfluidic platform was performed to tune the fluid flow profile and depth of ...

Abstract	Precisely controlling delivery of drugs and other reagents is important for intravital microscopy studies. In this work, photolithographic integration of micro-nozzles onto a microfluidic platform was performed to tune the fluid flow profile and depth of penetration into biological tissue mimics. Performance characteristics were measured by correlating the flow rate through the device to the applied pressure and/or delivery of dyes into solution and agarose gel-based phantom tissue. From these results, the implementation of micro-nozzles was demonstrated to significantly improve the lateral dispersion of delivered fluid and increase the depth of penetration into phantom tissue.
Language	English
Publishing date	2021-09-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2645443-9
ISSN	2159-6867 ; 2159-6859
ISSN (online)	2159-6867
ISSN	2159-6859
DOI	10.1557/s43579-021-00078-0
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Article: Biologically-derived nanomaterials for targeted therapeutic delivery to the brain.

Curley, Stephanie M / Cady, Nathaniel C

Science progress

2018 Volume 101, Issue 3, Page(s) 273–292

Abstract: Delivery of imaging agents and pharmaceutical payloads to the central nervous system (CNS) is essential for efficient diagnosis and treatment of brain diseases. However, therapeutic delivery is often restricted by the blood-brain barrier (BBB), which ... ...

Abstract	Delivery of imaging agents and pharmaceutical payloads to the central nervous system (CNS) is essential for efficient diagnosis and treatment of brain diseases. However, therapeutic delivery is often restricted by the blood-brain barrier (BBB), which prevents transport of clinical compounds to their region of interest. This review discusses the methods that have been used to avoid or overcome this barrier, presenting the use of biologically-derived nanomaterial systems as an efficient strategy for the diagnosis and treatment of CNS diseases. Biological nanomaterials have many advantages over synthetic systems, including being biodegradable, biocompatible, easily surface functionalised for conjugation of targeting moieties, and are often able to self-assemble. These abilities are discussed in relation to various systems, including liposomes, dendrimers, and viral nanoparticles.
MeSH term(s)	Animals ; Blood-Brain Barrier/metabolism ; Capillary Permeability ; Dendrimers/chemistry ; Dendrimers/pharmacokinetics ; Dendrimers/therapeutic use ; Drug Liberation ; Humans ; Nanoconjugates/chemistry ; Nanoconjugates/therapeutic use ; Nanoparticles/chemistry ; Nanoparticles/therapeutic use
Chemical Substances	Dendrimers ; Nanoconjugates
Language	English
Publishing date	2018-08-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	128412-5
ISSN	0036-8504 ; 0302-1785
ISSN	0036-8504 ; 0302-1785
DOI	10.3184/003685018X15306123582346
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Zs.B 731: Show issues

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Article ; Online: Interfacing neural cells with typical microelectronics materials for future manufacturing.

Pesantez Torres, Fernando / Tokranova, Natalya / Amodeo, Eleanor / Bertucci, Taylor / Kiehl, Thomas R / Xie, Yubing / Cady, Nathaniel C / Sharfstein, Susan T

Biosensors & bioelectronics

2023 Volume 242, Page(s) 115749

Abstract: The biocompatibility of materials used in electronic devices is critical for the development of implantable devices like pacemakers and neuroprosthetics, as well as in future biomanufacturing. Biocompatibility refers to the ability of these materials to ... ...

Abstract	The biocompatibility of materials used in electronic devices is critical for the development of implantable devices like pacemakers and neuroprosthetics, as well as in future biomanufacturing. Biocompatibility refers to the ability of these materials to interact with living cells and tissues without causing an adverse response. Therefore, it is essential to evaluate the biocompatibility of metals and semiconductor materials used in electronic devices to ensure their safe use in medical applications. Here, we evaluated the biocompatibility of a collection of diced silicon chips coated with a variety of metal thin films, interfacing them with different cell types, including murine mastocytoma cells in suspension culture, adherent NIH 3T3 fibroblasts, and human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs). All materials tested were biocompatible and showed the potential to support neural differentiation of iPSC-NPCs, creating an opportunity to use these materials in a scalable production of a range of biohybrid devices such as electronic devices to study neural behaviors and neuropathies.
MeSH term(s)	Humans ; Mice ; Animals ; Induced Pluripotent Stem Cells ; Cell Differentiation ; Biosensing Techniques ; Neurons/metabolism ; Neural Stem Cells
Language	English
Publishing date	2023-10-13
Publishing country	England
Document type	Journal Article
ZDB-ID	1011023-9
ISSN	1873-4235 ; 0956-5663
ISSN (online)	1873-4235
ISSN	0956-5663
DOI	10.1016/j.bios.2023.115749
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Zs.A 2275: Show issues

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Article: Surveilling cellular vital signs: toward label-free biosensors and real-time viability assays for bioprocessing

Rosenberg, Julian N / Cady, Nathaniel C

Current opinion in biotechnology. 2021 Oct., v. 71

2021

Abstract	Cell viability is an essential facet of mammalian and microbial bioprocessing. While robust methods of monitoring cellular health remain critically important to biomanufacturing and biofabrication, the complexity of advanced cell culture platforms often poses challenges for conventional viability assays. This review surveys novel approaches to discern the metabolic, morphological, and mechanistic hallmarks of living systems — spanning subcellular and multicellular scales. While fluorescent probes coupled with 3D image analysis generate rapid results with spatiotemporal detail, molecular techniques like viability PCR can distinguish live cells with genetic specificity. Notably, label-free biosensors can detect nuanced attributes of cellular vital signs with single-cell resolution via optical, acoustic, and electrical signals. Ultimately, efforts to integrate these modalities with automation, machine learning, and high-throughput workflows will lead to exciting new vistas across the cell viability landscape.
Keywords	acoustics ; automation ; biofabrication ; bioprocessing ; biosensors ; cell culture ; cell viability ; fluorescence ; image analysis ; landscapes ; mammals
Language	English
Dates of publication	2021-10
Size	p. 123-129.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1052045-4
ISSN	1879-0429 ; 0958-1669
ISSN (online)	1879-0429
ISSN	0958-1669
DOI	10.1016/j.copbio.2021.07.004
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Rapid and Quantitative Detection of Human Antibodies against the 2019 Novel Coronavirus SARS CoV2 and Its Variants as a Result of Vaccination and Infection.

Taubner, Benjamin / Peredo-Wende, Ruben / Ramani, Ananthakrishnan / Singh, Gurpreet / Strle, Klemen / Cady, Nathaniel C

Microbiology spectrum

2021 Volume 9, Issue 2, Page(s) e0089021

Abstract: Measuring the antibody response to 2019 SARS CoV2 is critical for diagnostic purposes, for monitoring the prevalence of infection, and for gauging the efficacy of the worldwide vaccination effort for COVID-19. In this study, a microchip-based grating- ... ...

Abstract	Measuring the antibody response to 2019 SARS CoV2 is critical for diagnostic purposes, for monitoring the prevalence of infection, and for gauging the efficacy of the worldwide vaccination effort for COVID-19. In this study, a microchip-based grating-coupled fluorescent plasmonic (GC-FP) assay was used to measure antibody levels that resulted from COVID-19 infection and vaccination. In addition, we measured the relative antibody binding toward antigens from the CoV2 virus variants strains B.1.1.7 (Alpha) and B.1.351 (Beta). Antibody levels against multiple antigens within the SARS CoV2 spike protein were significantly elevated for both vaccinated and infected individuals, while those against the nucleocapsid (N) protein were only elevated for infected individuals. GC-FP was effective for monitoring the IgG-based serological response to vaccination throughout the vaccination sequence and also resolved acute (within hours) increases in antibody levels. A significant decrease in antibody binding to antigens from the B.1.351 variant, but not B.1.1.7, was observed for all vaccinated subjects when measured by GC-FP compared to the 2019 SARS CoV2 antigens. These results were corroborated by competitive enzyme-linked immunosorbent assay (ELISA). Collectively, the findings suggest that GC-FP is a viable, rapid, and accurate method for measuring both overall antibody levels to SARS CoV2 and relative antibody binding to viral variants during infection or vaccination.
MeSH term(s)	Antibodies, Viral/blood ; Antibody Affinity/immunology ; Biosensing Techniques ; COVID-19/diagnosis ; COVID-19/immunology ; COVID-19 Vaccines/immunology ; Coronavirus Nucleocapsid Proteins/immunology ; Dried Blood Spot Testing/methods ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G/blood ; Phosphoproteins/immunology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; SARS-CoV-2/isolation & purification ; Spike Glycoprotein, Coronavirus/immunology
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; Coronavirus Nucleocapsid Proteins ; Immunoglobulin G ; Phosphoproteins ; Spike Glycoprotein, Coronavirus ; nucleocapsid phosphoprotein, SARS-CoV-2 ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-09-29
Publishing country	United States
Document type	Journal Article
ISSN	2165-0497
ISSN (online)	2165-0497
DOI	10.1128/Spectrum.00890-21
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Article ; Online: Smart fracture plate for quantifying fracture healing: Preliminary efficacy in a biomechanical model.

Ledet, Eric H / Caparaso, Sydney M / Stout, Madelyn / Cole, Keegan P / Liddle, Benjamin / Cady, Nathaniel C / Archdeacon, Michael T

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

2022 Volume 40, Issue 10, Page(s) 2414–2420

Abstract: The diagnosis of fracture nonunion following plate osteosynthesis is subjective and frequently ambiguous. Initially following osteosynthesis, loads applied to the bone are primarily transmitted through the plate. However, as callus stiffness increases, ... ...

Abstract	The diagnosis of fracture nonunion following plate osteosynthesis is subjective and frequently ambiguous. Initially following osteosynthesis, loads applied to the bone are primarily transmitted through the plate. However, as callus stiffness increases, the callus is able to bear load proportional to its stiffness while forces through the plate decrease. The purpose of this study was to use a "smart" fracture plate to distinguish between phases of fracture healing by measuring forces transmitted through the plate. A wireless force sensor and small adapter were placed on the outside of a distal femoral locking plate. The adapter converts the slight bending of the plate under axial load into a transverse force which is measurable by the sensor. An osteotomy was created and then plated in the distal femur of biomechanical Sawbones. Specimens were loaded to simulate single-leg stance first with the osteotomy defect empty (acute healing), then sequentially filled with silicone (early callus) and then polymethyl methacrylate (hard callus). There was a strong correlation between applied axial load and force measured by the "smart" plate. Data demonstrate statistically significant differences between each phase of healing with as little as 150 N of axial load applied to the femur. Forces measured in the plate were significantly different between acute (100%), early callus (66.4%), and hard callus (29.5%). This study demonstrates the potential of a "smart" fracture plate to distinguish between phases of healing. These objective data may enable early diagnosis of nonunion and enhance outcomes for patients.
MeSH term(s)	Biomechanical Phenomena ; Bone Plates ; Femoral Fractures/surgery ; Fracture Fixation, Internal ; Fracture Healing ; Humans ; Polymethyl Methacrylate ; Silicones
Chemical Substances	Silicones ; Polymethyl Methacrylate (9011-14-7)
Language	English
Publishing date	2022-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605542-4
ISSN	1554-527X ; 0736-0266
ISSN (online)	1554-527X
ISSN	0736-0266
DOI	10.1002/jor.25254
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