Hybrid negative enrichment of circulating tumor cells from whole blood in a 3D-printed monolithic device

Chu, Chia‐Heng; Liu, Ruxiu; Ozkaya‐Ahmadov, Tevhide; Boya, Mert; Swain, Brandi E.; Owens, Jacob M; Burentugs, Enerelt; Bilen, Mehmet Asım; McDonald, John F.; Sarioglu, A. Fatih

doi:10.1039/c9lc00575g

Cited by 35 publications

(28 citation statements)

References 62 publications

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“…Signal generation on the lateral flow assay was via color change in presence of 3,3 ,5,5 -Tetramethylbenzidine (TMB) substrate, magnetic nanoparticle probes modified with HRP and antibody resulted in generation of color spots at detection zones upon addition of colorimetric substrate ( Figure 10C). Sarioglu et al [112] constructed a hybrid 3D printed monolithic device for negative enrichment of circulating tumor cells from whole blood, by combining microfluidic immunoaffinity based cell capture and a membrane filter to enrich the captured circulating tumor cells for downstream applications. Microfluidic device was designed to have high surface area and increased interaction between white blood cells and functionalized surfaces with 4-32 stacked microfluidic layers and 200 µM diameter microposts ( Figure 10D).…”

Section: Hybrid 3d Printed Sensorsmentioning

confidence: 99%

“…3 µM membrane filter to retain all eluted nucleated cells for downstream applications. Reproduced with permission from [112]. Copyright (2019) The Royal Society of Chemistry (E) Images of 3D printed modular chips made from DLP based stereolithography based approach where monomeric resin is doped with acrylic acid to generate a platform that has intrinsic carboxylates for direct conjugation of biomolecules.…”

Section: Hybrid 3d Printed Sensorsmentioning

confidence: 99%

“…Sarioglu et al [ 112 ] constructed a hybrid 3D printed monolithic device for negative enrichment of circulating tumor cells from whole blood, by combining microfluidic immunoaffinity based cell capture and a membrane filter to enrich the captured circulating tumor cells for downstream applications. Microfluidic device was designed to have high surface area and increased interaction between white blood cells and functionalized surfaces with 4-32 stacked microfluidic layers and 200 µM diameter microposts ( Figure 10 D).…”

Section: Hybrid 3d Printed Sensorsmentioning

confidence: 99%

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3D-Printed Immunosensor Arrays for Cancer Diagnostics

Sharafeldin

Kadimisetty

Bhalerao

et al. 2020

Sensors

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Detecting cancer at an early stage of disease progression promises better treatment outcomes and longer lifespans for cancer survivors. Research has been directed towards the development of accessible and highly sensitive cancer diagnostic tools, many of which rely on protein biomarkers and biomarker panels which are overexpressed in body fluids and associated with different types of cancer. Protein biomarker detection for point-of-care (POC) use requires the development of sensitive, noninvasive liquid biopsy cancer diagnostics that overcome the limitations and low sensitivities associated with current dependence upon imaging and invasive biopsies. Among many endeavors to produce user-friendly, semi-automated, and sensitive protein biomarker sensors, 3D printing is rapidly becoming an important contemporary tool for achieving these goals. Supported by the widely available selection of affordable desktop 3D printers and diverse printing options, 3D printing is becoming a standard tool for developing low-cost immunosensors that can also be used to make final commercial products. In the last few years, 3D printing platforms have been used to produce complex sensor devices with high resolution, tailored towards researchers’ and clinicians’ needs and limited only by their imagination. Unlike traditional subtractive manufacturing, 3D printing, also known as additive manufacturing, has drastically reduced the time of sensor and sensor array development while offering excellent sensitivity at a fraction of the cost of conventional technologies such as photolithography. In this review, we offer a comprehensive description of 3D printing techniques commonly used to develop immunosensors, arrays, and microfluidic arrays. In addition, recent applications utilizing 3D printing in immunosensors integrated with different signal transduction strategies are described. These applications include electrochemical, chemiluminescent (CL), and electrochemiluminescent (ECL) 3D-printed immunosensors. Finally, we discuss current challenges and limitations associated with available 3D printing technology and future directions of this field.

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Section: Hybrid 3d Printed Sensorsmentioning

confidence: 99%

Section: Hybrid 3d Printed Sensorsmentioning

confidence: 99%

Section: Hybrid 3d Printed Sensorsmentioning

confidence: 99%

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3D-Printed Immunosensor Arrays for Cancer Diagnostics

Sharafeldin

Kadimisetty

Bhalerao

et al. 2020

Sensors

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“…The Cytophone platform uses an in vivo photoacoustic flow cytometry platform with a high pulse rate laser and focused ultrasound transducers for label-free detection of CTCs (113). Furthermore, there are separation methods that combine antibody capture with physical properties, such as CTC-iCHIP (86) and 3D-printed microfluidic devices (114), which capture CTCs more efficiently by combining antibody beads with CTC size filtration.…”

Section: Isolation and Detection Of Ctcsmentioning

confidence: 99%

Pathology of circulating tumor cells and the available capture tools (Review)

Guan

Tian

et al. 2020

Oncol Rep

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Circulating tumor cells (CTCs), are tumor cells that diffuse into the circulating blood and serve an important role in the progress of cancer. During the early stages of cancer, CTCs undergo an epithelial-mesenchymal transition and obtain a more invasive phenotype. Subsequently, the tumor cells enter the circulating blood with the aid of immune cells, and enter a dormant state upon reaching distal organs. As the tumor progresses, metastasis may occur under certain conditions. The capture technologies available for CTCs are based on antibody-based capture, or capture based on the physical properties of CTCs, as well as modern technologies that integrate both these methods. Emerging modern technologies have increased the accuracy and efficiency of tumor cell capture, and have thus improved our understanding of tumor cells, and the molecular mechanisms underlying their properties. CTCs serve an important role in disease progression, prediction of patient prognosis and individualized treatment. Contents 1. Introduction 2. Physiological processes of CTCs 3. Isolation and detection of CTCs 4. CTC associated research methods 5. Conclusion

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“…Depletion of white blood cells through immunocapture on functionalized device surfaces is often not practical for clinically-relevant volumes of blood because of the limited surface area available in a typical microfluidic device 40 . To increase the surface area available for the WBC immunocapture, we recently introduced an additively manufactured multi-layered microfluidic device, which still required WBCs to be prelabeled with biotin and relied on strong avidin–biotin interaction for depletion 41 .…”

Section: Introductionmentioning

confidence: 99%

Negative enrichment of circulating tumor cells from unmanipulated whole blood with a 3D printed device

Chu

Ozkaya‐Ahmadov

Swain

et al. 2021

Sci Rep

Self Cite

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Reliable and routine isolation of circulating tumor cells (CTCs) from peripheral blood would allow effective monitoring of the disease and guide the development of personalized treatments. Negative enrichment of CTCs by depleting normal blood cells ensures against a biased selection of a subpopulation and allows the assay to be applied on different tumor types. Here, we report an additively manufactured microfluidic device that can negatively enrich viable CTCs from clinically-relevant volumes of unmanipulated whole blood samples. Our device depletes nucleated blood cells based on their surface antigens and the smaller anucleated cells based on their size. Enriched CTCs are made available off the device in suspension making our technique compatible with standard immunocytochemical, molecular and functional assays. Our device could achieve a ~ 2.34-log depletion by capturing > 99.5% of white blood cells from 10 mL of whole blood while recovering > 90% of spiked tumor cells. Furthermore, we demonstrated the capability of the device to isolate CTCs from blood samples collected from patients (n = 15) with prostate and pancreatic cancers in a pilot study. A universal CTC assay that can differentiate tumor cells from normal blood cells with the specificity of clinically established membrane antigens yet require no label has the potential to enable routine blood-based tumor biopsies at the point-of-care.

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Hybrid negative enrichment of circulating tumor cells from whole blood in a 3D-printed monolithic device

Abstract: A monolithic 3D-printed microfluidic device integrated with stacked layers of functionalized leukodepletion channels and microfiltration for the negative enrichment of circulating tumor cells directly from clinically relevant volumes of whole blood.

Cited by 35 publications

References 62 publications

3D-Printed Immunosensor Arrays for Cancer Diagnostics

3D-Printed Immunosensor Arrays for Cancer Diagnostics

Pathology of circulating tumor cells and the available capture tools (Review)

Negative enrichment of circulating tumor cells from unmanipulated whole blood with a 3D printed device

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