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Pump-Free Microfluidic Hemofiltration Device.

ABSTRACT: Hemofiltration removes water and small molecules from the blood via nanoporous filtering membranes. This paper discusses a pump-free hemofiltration device driven by the pressure difference between the artery and the vein. In the design of the filtering device, oncotic pressure needs to be taken into consideration. Transmembrane pressure (TMP) determines the amount and direction of hemofiltration, which is calculated by subtracting the oncotic pressure from the blood pressure. Blood pressure decreases as the channels progress from the inlet to the outlet, while oncotic pressure increases slightly since no protein is removed from the blood to the filtrate in hemofiltration. When TMP is negative, the filtrate returns to the blood, i.e., backfiltration takes place. A small region of the device with negative TMP would thus result in a small amount of or even zero filtrates. First, we investigated this phenomenon using in vitro experiments. We then designed a hemofiltration system taking backfiltration into consideration. We divided the device into two parts. In the first part, the device has channels for the blood and filtrate with a nanoporous membrane. In the second part, the device does not have channels for filtration. This design ensures TMP is always positive in the first part and prevents backfiltration. The concept was verified using in vitro experiments and ex vivo experiments in beagle dogs. Given the simplicity of the device without pumps or electrical components, the proposed pump-free hemofiltration device may prove useful for either implantable or wearable hemofiltration.

SUBMITTER: Ito T

PROVIDER: S-EPMC8401791 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC-clusters). Existing technologies for CTC enrichment are designed primarily to isolate single CTCs, and while CTC-clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here, we developed a microchip technology (Cluster-Chip) specifically designed to capture CTC-clusters independent of tumor-specific markers from unprocessed blood. CTC-clusters are isolated through specialized bifurcating traps under low shear-stress conditions that preserve their integrity and even two-cell clusters are captured efficiently. Highly parallel architecture of the chip allows deterministic screening of clinically relevant volumes of blood samples at slow, and hence, non-damaging flow rates. Using the Cluster-Chip, we identify CTC-clusters in 30-40% of patients with metastatic cancers of the breast, prostate and melanoma. RNA sequencing of CTC-clusters confirms their tumor origin and identifies leukocytes within the clusters as being tissue-derived macrophages. Together, the development of a device for efficient capture of CTC-clusters will enable detailed characterization of their biological properties and role in cancer metastasis. We used the Cluster-Chip to capture CTC-clusters from the blood of a breast cancer patient with high CTC counts, released CTC-clusters in solution, stained them with TexasRed-conjugated antibodies against the leukocyte cell surface markers CD45, CD14 and CD16, and then isolated intact CTC-clusters individually using a micromanipulator. From a single time point, we retrieved 15 CTC-clusters, and each of those clusters was individually subjected to RNA-sequencing analysis using a next generation platform (SOLiD 5500). In addition, two leukocytes were isolated from the blood of a healthy donor were individually subjected to RNA-sequencing analysis using the same platform.

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Pump-Free Microfluidic Hemofiltration Device.

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