Microelectrofluidic probe for sequential cell separation and patterning

Brimmo, Ayoola T.; Menachery, Anoop; Qasaimeh, Mohammad A.

doi:10.1039/c9lc00748b

Cited by 18 publications

(11 citation statements)

References 41 publications

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“…In addition, the estimated average shear stresses within channels were <2 Pa ( Fig. 1f), which are expected not to jeopardize the captured cells remaining intact within the channels 16 . Finally, micromixing as well as cell intactness were experimentally verified by the flow patterns of cells spiked into blood samples ( Fig.…”

Section: Visualization Of the Flow And Shearmentioning

confidence: 94%

AFM-compatible microfluidic platform for affinity-based capture and nanomechanical characterization of circulating tumor cells

Deliorman¹,

Janahi

Sukumar³

et al. 2020

Microsyst Nanoeng

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Circulating tumor cells (CTCs) carried by the patient's bloodstream are known to lead to the metastatic spread of cancer. It is becoming increasingly clear that an understanding of the nanomechanical characteristics of CTCs, such as elasticity and adhesiveness, represents advancements in tracking and monitoring cancer progression and metastasis. In the present work, we describe a combined microfluidic-atomic force microscopy (AFM) platform that uses antibody-antigen capture to routinely isolate and nanomechanically characterize CTCs present in blood samples from prostate cancer patients. We introduce the reversible assembly of a microfluidic device and apply refined and robust chemistry to covalently bond antibodies onto its glass substrate with high density and the desired orientation. As a result, we show that the device can efficiently capture CTCs from patients with localized and metastatic prostate cancer through anti-EpCAM, anti-PSA, and anti-PSMA antibodies, and it is suitable for AFM measurements of captured intact CTCs. When nanomechanically characterized, CTCs originating from metastatic cancer demonstrate decreased elasticity and increased deformability compared to those originating from localized cancer. While the average adhesion of CTCs to the AFM tip surface remained the same in both the groups, there were fewer multiple adhesion events in metastatic CTCs than there were in their counterparts. The developed platform is simple, robust, and reliable and can be useful in the diagnosis and prognosis of prostate cancer as well as other forms of cancer.

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Section: Visualization Of the Flow And Shearmentioning

confidence: 94%

AFM-compatible microfluidic platform for affinity-based capture and nanomechanical characterization of circulating tumor cells

Deliorman¹,

Janahi

Sukumar³

et al. 2020

Microsyst Nanoeng

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“…The different intrinsic features of cell populations, including their density [55], size [56], compressibility [57], deformability [58], dielectric properties [59], and viscosity [60], are used to physically separate CTCs [61,62]. Deterministic lateral displacement, inertial microfluidics, micropores, micropillar arrays, vortex-mediated deformability cytometry (VDC), inertial focusing dielectrophoresis, acoustic waves, and optical approaches have all been reported for the detection and separation of CTCs [63][64][65][66][67][68][69]. Biological approaches, on the other hand, rely on specific surface proteins produced on tumor cells to act as molecular recognizers such as transferrin, peptides, sialic acid, and antibodies to trap and isolate CTCs [70][71][72].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Microfluidic Platform for Physical and Immunological Detection and Capture of Circulating Tumor Cells

et al. 2022

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CTCs (circulating tumor cells) are well-known for their use in clinical trials for tumor diagnosis. Capturing and isolating these CTCs from whole blood samples has enormous benefits in cancer diagnosis and treatment. In general, various approaches are being used to separate malignant cells, including immunomagnets, macroscale filters, centrifuges, dielectrophoresis, and immunological approaches. These procedures, on the other hand, are time-consuming and necessitate multiple high-level operational protocols. In addition, considering their low efficiency and throughput, the processes of capturing and isolating CTCs face tremendous challenges. Meanwhile, recent advances in microfluidic devices promise unprecedented advantages for capturing and isolating CTCs with greater efficiency, sensitivity, selectivity and accuracy. In this regard, this review article focuses primarily on the various fabrication methodologies involved in microfluidic devices and techniques specifically used to capture and isolate CTCs using various physical and biological methods as well as their conceptual ideas, advantages and disadvantages.

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“…The capture efficiency is strongly related with the magnitude of shear stresses, which is also greatly influenced by the separation distance “d” between the HB‐MFP mesa and the capture substrate. [ 36 ] To investigate this effect on the cell capture efficiency, the HB‐MFP was positioned at 25, 50, 75, and 100 µm distances above the substrate and a suspension of PC3 cells was injected on an anti‐EpCAM‐activated glass at 1.2 mL h ‐1 flow rate. As apparent in Figure 3d, with increasing separation distances, the cell capture efficiency increases until a maximum is reached, and then starts dropping down.…”

Section: Resultsmentioning

confidence: 99%

“…[30] Nevertheless, since their first introduction, [31] the MFPs have already been deployed in several applications, such as cell stimulation [32] and manipulation. [33,34] More recently, we have developed 3D printing methodologies to manufacture MFPs with great modular capability in the design, [35,36] thus easing the implementation of new concepts and applications with simple design adjustments.…”

Section: In This Work For First Time Circulating Tumor Cells (Ctcs) A...mentioning

confidence: 99%

Herringbone Microfluidic Probe for Multiplexed Affinity‐Capture of Prostate Circulating Tumor Cells

Glia

Deliorman

Sukumar

et al. 2021

Adv Materials Technologies

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In this work, for first time, circulating tumor cells (CTCs) are captured on an open biofunctionalized substrate with multiplexing capability. This is achieved by developing a new microfluidic probe (MFP) integrated with radially staggered herringbone (HB) elements for microvortex generation. The new tool, named as herringbone microfluidic probe (HB‐MFP), is a channel‐less microfluidic system with physically separated bottom capture substrate and top fluidics delivery system. The concept allows for functionalizing the capture substrate with multiple biorecognition ligands (in this work, stripes of different capture antibodies) and scanning the fluidics delivery system across the substrate in a 2D printing‐like movement. Using the HB‐MFP, CTCs are efficiently captured from prostate cancer blood samples through their specific EpCAM, PSMA, and PSA antigens in a single run, with counts ranging from as low as 6 CTCs mL‐1 (localized cancer patients) to as high as 280 CTCs mL‐1 (metastatic cancer patients). In the process, CTC clusters with sizes of as high as 40–50 cells are also successfully captured. The results indicate that multiplex profiles of CTCs could reveal certain cellular phenotypes based on PSMA and PSA expression levels. The developed HB‐MFP is simple and robust to use, allows for high throughput sample processing, and provides seamless access to captured CTCs for further downstream characterization.

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Microelectrofluidic probe for sequential cell separation and patterning

Abstract: Cell separation and patterning are of great interest to numerous biomedical applications. This work presents the microelectrofluidic probe, which separates cells within an open microfluidic system, and patterns cells in a 2D printing approach.

Cited by 18 publications

References 41 publications

AFM-compatible microfluidic platform for affinity-based capture and nanomechanical characterization of circulating tumor cells

AFM-compatible microfluidic platform for affinity-based capture and nanomechanical characterization of circulating tumor cells

Recent Advances in Microfluidic Platform for Physical and Immunological Detection and Capture of Circulating Tumor Cells

Herringbone Microfluidic Probe for Multiplexed Affinity‐Capture of Prostate Circulating Tumor Cells

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