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Mandenius, Carl-FredrikORCID iD iconorcid.org/0000-0001-9711-794x
Alternative names
Publications (10 of 99) Show all publications
Park, C., Lim, W., Song, R., Han, J., You, D., Kim, S., . . . Park, S. (2024). Efficient separation of large particles and giant cancer cells using an isosceles trapezoidal spiral microchannel. The Analyst, 149(17), 4496-4505
Open this publication in new window or tab >>Efficient separation of large particles and giant cancer cells using an isosceles trapezoidal spiral microchannel
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2024 (English)In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 149, no 17, p. 4496-4505Article in journal (Refereed) Published
Abstract [en]

Polyploid giant cancer cells (PGCCs) contribute to the genetic heterogeneity and evolutionary dynamics of tumors. Their size, however, complicates their isolation from mainstream tumor cell populations. Standard techniques like fluorescence-activated cell sorting (FACS) rely on fluorescent labeling, introducing potential challenges in subsequent PGCC analyses. In response, we developed the Isosceles Trapezoidal Spiral Microchannel (ITS mu C), a microfluidic device optimizing the Dean drag force (FD) and exploiting uniform vortices for enhanced separation. Numerical simulations highlighted ITS mu C's advantage in producing robust FD compared to rectangular and standard trapezoidal channels. Empirical results confirmed its ability to segregate larger polystyrene (PS) particles (avg. diameter: 50 mu m) toward the inner wall, while directing smaller ones (avg. diameter: 23 mu m) outward. Utilizing ITS mu C, we efficiently isolated PGCCs from doxorubicin-resistant triple-negative breast cancer (DOXR-TNBC) and patient-derived cancer (PDC) cells, achieving outstanding purity, yield, and viability rates (all greater than 90%). This precision was accomplished without fluorescent markers, and the versatility of ITS mu C suggests its potential in differentiating a wide range of heterogeneous cell populations. Polyploid giant cancer cells (PGCCs) contribute to the genetic heterogeneity and evolutionary dynamics of tumors.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2024
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:liu:diva-206321 (URN)10.1039/d4an00750f (DOI)001275477100001 ()39049608 (PubMedID)
Note

Funding Agencies|Korea-Sweden Cooperation Program through STINT (the Swedish Foundation for International Cooperation in Research and Higher Education); National Research Foundation (NRF) through the Ministry of Science and ICT (MSIT) of Korea [RS-2023-00218543, RS-2023-00242443]; National Research Council of Science & Technology (NST) [CRC22021-200]

Available from: 2024-08-15 Created: 2024-08-15 Last updated: 2025-02-18Bibliographically approved
Tran, T., Martinsson, E., Vargas, S., Lundström, I., Mandenius, C.-F. & Aili, D. (2022). Nanoplasmonic Avidity-Based Detection and Quantification of IgG Aggregates. Analytical Chemistry, 94(45), 15754-15762
Open this publication in new window or tab >>Nanoplasmonic Avidity-Based Detection and Quantification of IgG Aggregates
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2022 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 94, no 45, p. 15754-15762Article in journal (Refereed) Published
Abstract [en]

Production of therapeutic monoclonal antibodies (mAbs) is a complex process that requires extensive analytical and bioanalytical characterization to ensure high and consistent product quality. Aggregation of mAbs is common and very problematic and can result in products with altered pharmacodynamics and pharmacokinetics and potentially increased immunogenicity. Rapid detection of aggregates, however, remains very challenging using existing analytical techniques. Here, we show a real-time and label-free fiber optical nanoplasmonic biosensor system for specific detection and quantification of immunoglobulin G (IgG) aggregates exploiting Protein A mediated avidity effects. Compared to monomers, IgG aggregates were found to have substantially higher apparent affinity when binding to Protein Afunctionalized sensor chips in a specific pH range (pH 3.8-4.0). Under these conditions, aggregates and monomers showed significantly different binding and dissociation kinetics. Reliable and rapid aggregate quantification was demonstrated with a limit of detection (LOD) and limit of quantification (LOQ) of about 9 and 30 mu g/mL, respectively. Using neural network-based curve fitting, it was further possible to simultaneously quantify monomers and aggregates for aggregate concentrations lower than 30 mu g/mL. Our work demonstrates a unique avidity-based biosensor approach for fast aggregate analysis that can be used for rapid at-line quality control, including lot/batch release testing. This technology can also likely be further optimized for real-time in-line monitoring of product titers and quality, facilitating process intensification and automation.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2022
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:liu:diva-190352 (URN)10.1021/acs.analchem.2c03446 (DOI)000884793100001 ()36318700 (PubMedID)
Note

Funding Agencies|Swedish Innovation Agency (VINNOVA); Swedish Research Council [2016-04120, 2019-00130]; European Union [841373]

Available from: 2022-12-06 Created: 2022-12-06 Last updated: 2023-11-07Bibliographically approved
Tran, T., Martinsson, E., Gustavsson, R., Tronarp, O., Nilsson, M., Hansson, K. R., . . . Aili, D. (2022). Process integrated biosensors for real-time monitoring of antibodies for automated affinity purification. Analytical Methods, 14(44), 4555-4562
Open this publication in new window or tab >>Process integrated biosensors for real-time monitoring of antibodies for automated affinity purification
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2022 (English)In: Analytical Methods, ISSN 1759-9660, E-ISSN 1759-9679, Vol. 14, no 44, p. 4555-4562Article in journal (Refereed) Published
Abstract [en]

Therapeutic monoclonal antibodies (mAbs) provide new means for treatments of a wide range of diseases and comprise a large fraction of all new approved drugs. Production of mAbs is expensive compared to conventional drug production, primarily due to the complex processes involved. The affinity purification step is dominating the cost of goods in mAb manufacturing. Process intensification and automation could reduce costs, but the lack of real-time process analytical technologies (PAT) complicates this development. We show a specific and robust fiber optical localized surface plasmon resonance (LSPR) sensor technology that is optimized for in-line product detection in the effluent in affinity capture steps. The sensor system comprises a flow cell and a replaceable sensor chip functionalized with biorecognition elements for specific analyte detection. The high selectivity of the sensor enable detection of mAbs in complex sample matrices at concentrations below 2.5 mu g mL(-1). In place regeneration of the sensor chips allowed for continuous monitoring of multiple consecutive chromatographic separation cycles. Excellent performance was obtained at different purification scales with flow rates up to 200 mL min(-1). This sensor technology facilitates efficient column loading, optimization, and control of chromatography systems, which can pave the way for continuous operation and automation of protein purification steps.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2022
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:liu:diva-189942 (URN)10.1039/d2ay01567f (DOI)000877122600001 ()36314900 (PubMedID)
Note

Funding Agencies|European Unions Horizon 2020 research and innovation program under the Marie Skodowska-Curie grant [841373]; Swedish Innovation Agency (VINNOVA) [2016-04120, 2019-00130]

Available from: 2022-11-15 Created: 2022-11-15 Last updated: 2023-05-09Bibliographically approved
Mandenius, C.-F. (2021). Measurement Technologies for Upstream and Downstream Bioprocessing. Processes, 9(1), Article ID 143.
Open this publication in new window or tab >>Measurement Technologies for Upstream and Downstream Bioprocessing
2021 (English)In: Processes, ISSN 2227-9717, Vol. 9, no 1, article id 143Article in journal, Editorial material (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
MDPI, 2021
National Category
Bioprocess Technology
Identifiers
urn:nbn:se:liu:diva-173430 (URN)10.3390/pr9010143 (DOI)000610777800001 ()
Available from: 2021-02-20 Created: 2021-02-20 Last updated: 2021-02-23
Randek, J. & Mandenius, C.-F. (2020). In situ scanning capacitance sensor with spectral analysis reveals morphological states in cultures for production of biopharmaceuticals. Sensors and actuators. B, Chemical, 313, Article ID 128052.
Open this publication in new window or tab >>In situ scanning capacitance sensor with spectral analysis reveals morphological states in cultures for production of biopharmaceuticals
2020 (English)In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 313, article id 128052Article in journal (Refereed) Published
Abstract [en]

In situ capacitance sensing is shown to be capable of monitoring critical morphological changes in industrial cultures by analyzing the sensor’s frequency spectrum. Scanning the frequency of an alternating current between the electrodes of a capacitance sensor, placed in a cell culture, allowed detection of the size change of microbial cells from shifts in the spectra. The frequency was scanned between 0.1–15 MHz and cell size was measured from 1 to 20 μm. The analysis of the spectra was verified with two recombinant strains, one producing human insulin and another Green Fluorescence Protein (GFP). Both the insulin and GFP cultivations were carried out in 6 L fed-batch bioreactors using typical industrial procedures. The spectral analysis provided critical information about the changes in the size of the cells. It is suggested that this information may have high relevance for a better assessment of the state of cultivations producing proteins, for optimization and for improving the economy of large-scale biopharmaceutical production.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Recombinant protein, Impedance, Capacitance, Dielectric spectroscopy, Frequency scanning, Cell growth
National Category
Pharmaceutical and Medical Biotechnology
Identifiers
urn:nbn:se:liu:diva-165090 (URN)10.1016/j.snb.2020.128052 (DOI)000526287200017 ()2-s2.0-85082736277 (Scopus ID)
Note

Funding agencies: European Unions Horizon 2020 research and innovation program under the Marie Sklodowska-Curie actions grantEuropean Union (EU) [643056]

Available from: 2020-04-15 Created: 2020-04-15 Last updated: 2025-02-10Bibliographically approved
Theuer, L., Randek, J., Junne, S., Neubauer, P., Mandenius, C.-F. & Beni, V. (2020). Single-use printed biosensor for l-lactate and its application in bioprocess monitoring. Processes, 8(3), Article ID 321.
Open this publication in new window or tab >>Single-use printed biosensor for l-lactate and its application in bioprocess monitoring
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2020 (English)In: Processes, ISSN 2227-9717, Vol. 8, no 3, article id 321Article in journal (Refereed) Published
Abstract [en]

There is a profound need in bioprocess manufacturing for low-cost single-use sensors that allow timely monitoring of critical product and production attributes. One such opportunity is screen-printed enzyme-based electrochemical sensors, which have the potential to enable low-cost online and/or off-line monitoring of specific parameters in bioprocesses. In this study, such a singleuse electrochemical biosensor for lactate monitoring is designed and evaluated. Several aspects of its fabrication and use are addressed, including enzyme immobilization, stability, shelf-life and reproducibility. Applicability of the biosensor to off-line monitoring of bioprocesses was shown by testing in two common industrial bioprocesses in which lactate is a critical quality attribute (Corynebacterium fermentation and mammalian Chinese hamster ovary (CHO) cell cultivation). The specific response to lactate of the screen-printed biosensor was characterized by amperometric measurements. The usability of the sensor at typical industrial culture conditions was favorably evaluated and benchmarked with commonly used standard methods (HPLC and enzymatic kits). The single-use biosensor allowed fast and accurate detection of lactate in prediluted culture media used in industrial practice. The design and fabrication of the biosensor could most likely be adapted to several other critical bioprocess analytes using other specific enzymes. This makes this single-use screen-printed biosensor concept a potentially interesting and versatile tool for further applications in bioprocess monitoring. © 2020 by the authors.

Place, publisher, year, edition, pages
MDPI, 2020
Keywords
At-line measurement, Enzyme electrode, In-line monitoring, Lactate biosensor, Off-line monitoring, Screen-printing
National Category
Bioprocess Technology
Identifiers
urn:nbn:se:liu:diva-165115 (URN)10.3390/pr8030321 (DOI)000525842000066 ()2-s2.0-85081985509 (Scopus ID)
Note

Funding agencies: European Unions Horizon 2020 research and innovation program under the Marie Sklodowska-Curie actions grantEuropean Union (EU) [643056]

Available from: 2020-04-15 Created: 2020-04-15 Last updated: 2020-04-27Bibliographically approved
Christoffersson, J., Aronsson, C., Jury, M., Selegård, R., Aili, D. & Mandenius, C.-F. (2019). Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device. Biofabrication, 11(1), 1-13, Article ID 015013.
Open this publication in new window or tab >>Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device
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2019 (English)In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 11, no 1, p. 1-13, article id 015013Article in journal (Refereed) Published
Abstract [en]

Liver cell culture models are attractive in both tissue engineering and for development of assays for drug toxicology research. To retain liver specific cell functions, the use of adequate cell types and culture conditions, such as a 3D orientation of the cells and a proper supply of nutrients and oxygen, are critical. In this article, we show how extracellular matrix mimetic hydrogels can support hepatocyte viability and functionality in a perfused liver-on-a-chip device. A modular hydrogel system based on hyaluronan and poly(ethylene glycol) (HA-PEG), modified with cyclooctyne moieties for bioorthogonal strain-promoted alkyne-azide 1, 3-dipolar cycloaddition (SPAAC), was developed, characterized, and compared for cell compatibility to hydrogels based on agarose and alginate. Hepatoma cells (HepG2) formed spheroids with viable cells in all hydrogels with the highest expression of albumin and urea in alginate hydrogels. By including an excess of cyclooctyne in the HA backbone, azide-modified cell adhesion motifs (linear and cyclic RGD peptides) could be introduced in order to enhance viability and functionality of human induced pluripotent stem cell derived hepatocytes (hiPS-HEPs). In the HA-PEG hydrogels modified with cyclic RGD peptides hiPS-HEPs migrated and grew in 3D and showed an increased viability and higher albumin production compared to when cultured in the other hydrogels. This flexible SPAAC crosslinked hydrogel system enabled fabrication of perfused 3D cell culture of hiPS-HEPs and is a promising material for further development and optimization of liver-on-a-chip devices.

Place, publisher, year, edition, pages
Institute of Physics (IOP), 2019
National Category
Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cell Biology
Identifiers
urn:nbn:se:liu:diva-154008 (URN)10.1088/1758-5090/aaf657 (DOI)000454550900002 ()
Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2022-04-29Bibliographically approved
Christoffersson, J., Meier, F., Kempf, H., Schwanke, K., Coffee, M., Beilmann, M., . . . Mandenius, C.-F. (2018). A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device. Bioengineering, 5(2), 1-13, Article ID 36.
Open this publication in new window or tab >>A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device
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2018 (English)In: Bioengineering, E-ISSN 2306-5354, Vol. 5, no 2, p. 1-13, article id 36Article in journal (Refereed) Published
Abstract [en]

Three-dimensional (3D) models with cells arranged in clusters or spheroids have emerged as valuable tools to improve physiological relevance in drug screening. One of the challenges with cells cultured in 3D, especially for high-throughput applications, is to quickly and non-invasively assess the cellular state in vitro. In this article, we show that the number of cells growing out from human induced pluripotent stem cell (hiPSC)-derived cardiac spheroids can be quantified to serve as an indicator of a drug’s effect on spheroids captured in a microfluidic device. Combining this spheroid-on-a-chip with confocal high content imaging reveals easily accessible, quantitative outgrowth data. We found that effects on outgrowing cell numbers correlate to the concentrations of relevant pharmacological compounds and could thus serve as a practical readout to monitor drug effects. Here, we demonstrate the potential of this semi-high-throughput “cardiac cell outgrowth assay” with six compounds at three concentrations applied to spheroids for 48 h. The image-based readout complements end-point assays or may be used as a non-invasive assay for quality control during long-term culture.

National Category
Cell and Molecular Biology Biomedical Laboratory Science/Technology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-154007 (URN)10.3390/bioengineering5020036 (DOI)
Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-03-29Bibliographically approved
Bengtsson, K., Christoffersson, J., Mandenius, C.-F. & Robinson, N. D. (2018). A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices. Microfluidics and Nanofluidics, 22(3), Article ID 27.
Open this publication in new window or tab >>A clip-on electroosmotic pump for oscillating flow in microfluidic cell culture devices
2018 (English)In: Microfluidics and Nanofluidics, ISSN 1613-4982, E-ISSN 1613-4990, Vol. 22, no 3, article id 27Article in journal (Refereed) Published
Abstract [en]

Recent advances in microfluidic devices put a high demand on small, robust and reliable pumps suitable for high-throughput applications. Here we demonstrate a compact, low-cost, directly attachable (clip-on) electroosmotic pump that couples with standard Luer connectors on a microfluidic device. The pump is easy to make and consists of a porous polycarbonate membrane and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) electrodes. The soft electrode and membrane materials make it possible to incorporate the pump into a standard syringe filter holder, which in turn can be attached to commercial chips. The pump is less than half the size of the microscope slide used for many commercial lab-on-a-chip devices, meaning that these pumps can be used to control fluid flow in individual reactors in highly parallelized chemistry and biology experiments. Flow rates at various electric current and device dimensions are reported. We demonstrate the feasibility and safety of the pump for biological experiments by exposing endothelial cells to oscillating shear stress (up to 5 dyn/cm2) and by controlling the movement of both micro- and macroparticles, generating steady or oscillatory flow rates up to ± 400 μL/min.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2018
National Category
Other Medical Biotechnology
Identifiers
urn:nbn:se:liu:diva-145301 (URN)10.1007/s10404-018-2046-4 (DOI)000427527600005 ()
Note

Funding agencies: Swedish Research Council (Vetenskapsradet) [2015-03298]

Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2019-01-22Bibliographically approved
Randek, J. & Mandenius, C.-F. (2018). On-line soft sensing in upstream bioprocessing. Critical reviews in biotechnology, 38(1), 106-121
Open this publication in new window or tab >>On-line soft sensing in upstream bioprocessing
2018 (English)In: Critical reviews in biotechnology, ISSN 0738-8551, E-ISSN 1549-7801, Vol. 38, no 1, p. 106-121Article, review/survey (Refereed) Published
Abstract [en]

This review provides an overview and a critical discussion of novel possibilities of applying soft sensors for on-line monitoring and control of industrial bioprocesses. Focus is on bio-product formation in the upstream process but also the integration with other parts of the process is addressed. The term soft sensor is used for the combination of analytical hardware data (from sensors, analytical devices, instruments and actuators) with mathematical models that create new real-time information about the process. In particular, the review assesses these possibilities from an industrial perspective, including sensor performance, information value and production economy. The capabilities of existing analytical on-line techniques are scrutinized in view of their usefulness in soft sensor setups and in relation to typical needs in bioprocessing in general. The review concludes with specific recommendations for further development of soft sensors for the monitoring and control of upstream bioprocessing.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Biomanufacturing; biotechnology; bioreactor monitoring; in situ measurement; real-time analysis
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-145254 (URN)10.1080/07388551.2017.1312271 (DOI)000423834000008 ()28423945 (PubMedID)
Note

Funding Agencies|EU-Horizon Marie Sklodowska-Curie Innovative Training Network BIORAPID [643056]; Linkoping University

Available from: 2018-03-07 Created: 2018-03-07 Last updated: 2020-04-15
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ORCID iD: ORCID iD iconorcid.org/0000-0001-9711-794x

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