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Nonsurgical bleeding occurs in a significant proportion of patients implanted with continuous-flow ventricular assist devices (CF-VADs) and is associated with nonphysiologic flow with diminished pulsatility. An in vitrovascular pulse perfusion model seeded with adult human aortic endothelial cells (HAECs) was used to identify biomarkers sensitive to changes in pulsatility. Diminished pulsatility resulted in an ~45% decrease in von Willebrand factor (vWF) levels from 9.80 to 5.32 ng/ml (n = 5, p< 0.05) and a threefold increase in angiopoietin-2 (ANGPT-2) levels from 775.29 to 2471.93 pg/ml (n = 5, p< 0.05) in cultured HAECs. These changes are in agreement with evaluation of patient blood samples obtained pre-CF-VAD implant and 30-day postimplant: a decrease in plasma vWF level by 50% from ~45.59 to ~22.49 μg/ml (n = 15, p< 0.01) and a 64% increase in plasma ANGPT-2 level from 7,073 to 11,615 pg/ml (n = 8, p< 0.05). This study identified vWF and ANGPT-2 as highly sensitive to changes in pulsatility, in addition to interleukin-6 (IL-6), IL-8, and tumor necrosis-α (TNF-α). These biomarkers may help determine the optimal level of pulsatility and help identify patients at high risk of nonsurgical bleeding.

Patients with metabolic dysfunction-associated steatohepatitis (MASH) are at an increased risk of developing venous thromboembolic events, including deep vein thrombosis (DVT). To date, the study of DVT in MASH has been hampered by the lack of reliable models that mimic the pathologic aspects of human disease.

Astronauts participating in long duration space missions are likely to be exposed to ionizing radiation associated with highly energetic and charged heavy particles. Previously proposed gene biomarkers for radiation exposure include phosphorylated H2A Histone Family, Member X (γH2AX), Tumor Protein 53 (TP53), and Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A). However, transcripts of these genes may not be the most suitable biomarkers for radiation exposure due to a lack of sensitivity or specificity. As part of a larger effort to develop lab-on-a-chip methods for detecting radiation exposure events using blood samples, we designed a dose–course microarray study in order to determine coding and non-coding RNA transcripts undergoing differential expression immediately following radiation exposure. The main goal was to elicit a small set of sensitive and specific radiation exposure biomarkers at low, medium, and high levels of ionizing radiation exposure. Four separate levels of radiation were considered: 0Gray (Gy) control; 0.3Gy; 1.5Gy; and 3.0Gy with four replicates at each radiation level. This report includes raw gene expression data files from the resulting microarray experiments from all three radiation levels ranging from a lower, typical exposure than an astronaut might see (0.3Gy) to high, potentially lethal, levels of radiation (3.0Gy). The data described here is available in NCBI's Gene Expression Omnibus (GEO), accession GSE64375.

In the body, osteocytes reside in lacunae, lenticular shaped cavities within mineralized bone. These cells are linked to each other and surface-residing osteoblasts via physical channels known as gap junctions. It has been suggested that osteocytes sense mechanical load applied to bone and relay that signal to osteoclasts and osteoblasts. Current in vitro and in vivo models of mechanotransduction face temporal and spatial barriers. Recent advances in polydimethylsiloxane (PDMS) based microfabrication techniques may be able to overcome some of these hurdles. However, before the bone research field can effectively utilize microsystems techniques, fundamental groundwork must be completed. This study characterized the behaviour of osteocytes on PDMS coated with collagen type I (CTI) and provides the framework for bone cell mechanotransduction studies using microsystems. The goal was to determine whether osteocytes were adversely affected by the substrate material by comparing their behaviour to a standard glass substrate. In addition, optimal culture conditions and time points for growing osteocytes on PDMS substrates were determined. Results of this study suggested that use of PDMS does not adversely affect osteocyte behaviour. Furthermore, the results demonstrated that osteocytes should be cultured for no less than 72 hours prior to experimentation to allow the establishment and maintenance of phenotypic characteristics. These results completed essential groundwork necessary for further studies regarding osteocytes in microsystems modelling utilizing PDMS.

Circulating tumor cells (CTC) are cells that have detached from primary tumors and circulate in the bloodstream where they are carried to other organs, leading to seeding of new tumors and metastases. CTC have been known to exist in the bloodstream for more than a century. With recent progress in the area of micro- and nanotechnology, it has been possible to adopt new approaches in CTC research. Microscale and nanoscale studies can throw some light on the time course of CTC appearance in blood and CTC overexpression profiles for cancer-related markers and galvanize the development of drugs to block metastases. CTC counts could serve as endpoint biomarkers and as prognostic markers for patients with a metastatic disease. This paper reviews some of the recent researches on using micro- and nanotechnology to capture and profile CTC.

In the body, osteocytes reside in lacunae, lenticular shaped cavities within mineralized bone. These cells are linked to each other and surface-residing osteoblasts via physical channels known as gap junctions. It has been suggested that osteocytes sense mechanical load applied to bone and relay that signal to osteoclasts and osteoblasts. Current in vitro and in vivo models of mechanotransduction face temporal and spatial barriers. Recent advances in polydimethylsiloxane (PDMS) based microfabrication techniques may be able to overcome some of these hurdles. However, before the bone research field can effectively utilize microsystems techniques, fundamental groundwork must be completed. This study characterized the behaviour of osteocytes on PDMS coated with collagen type I (CTI) and provides the framework for bone cell mechanotransduction studies using microsystems. The goal was to determine whether osteocytes were adversely affected by the substrate material by comparing their behaviour to a standard glass substrate. In addition, optimal culture conditions and time points for growing osteocytes on PDMS substrates were determined. Results of this study suggested that use of PDMS does not adversely affect osteocyte behaviour. Furthermore, the results demonstrated that osteocytes should be cultured for no less than 72 hours prior to experimentation to allow the establishment and maintenance of phenotypic characteristics. These results completed essential groundwork necessary for further studies regarding osteocytes in microsystems modelling utilizing PDMS.

Native heart consists of myocytes and non-myocytes. We demonstrate here the feasibility of a size-based microfluidic separation of myocytes and non-myocytes from the neonatal rat myocardium. The device consists of a middle channel (50 μm wide, 200 μm tall, and 4 cm long) connected to adjacent side channels by microsieves (80 μm wide, 5 μm tall and 40 μm in length). The side channels increase in width in a flared shape along the length of the device to ensure constant pressure gradient across all sieves. In the first step, non-myoctes were removed from the myocytes by a conventional pre-plating method for 75 min. Subsequently, the non-myocytes were further enriched in a microfludic device at 20 μl/min. We demonstrated that the cells in the middle and side channels maintained viability during sorting and the ability to attach and grow in culture. Upon culture for 48 h cardiomyocytes from the reservoir (control) and middle channel stained positive for cardiac Troponin I, exhibited a well developed contractile apparatus and contracted spontaneously and in response to electrical field stimulation. Most of the cells in the side channel expressed a non-myocyte marker vimetin. Fluorescent activated cell sorting indicated significant enrichment in the side channel (p< 0.001) for non-myocytes. Original cell suspension had a bimodal cell size distribution with the peaks in the range from 7–9 μm and 15–17 μm. Upon cell sorting the distribution was Gaussian in both side channel and middle channel with the peaks in the range 7–9 μm and 9–11 μm respectively, indicating that the separation by size occurred.Native heart consists of myocytes and non-myocytes. We demonstrate here the feasibility of a size-based microfluidic separation of myocytes and non-myocytes from the neonatal rat myocardium. The device consists of a middle channel (50 μm wide, 200 μm tall, and 4 cm long) connected to adjacent side channels by microsieves (80 μm wide, 5 μm tall and 40 μm in length). The side channels increase in width in a flared shape along the length of the device to ensure constant pressure gradient across all sieves. In the first step, non-myoctes were removed from the myocytes by a conventional pre-plating method for 75 min. Subsequently, the non-myocytes were further enriched in a microfludic device at 20 μl/min. We demonstrated that the cells in the middle and side channels maintained viability during sorting and the ability to attach and grow in culture. Upon culture for 48 h cardiomyocytes from the reservoir (control) and middle channel stained positive for cardiac Troponin I, exhibited a well developed contractile apparatus and contracted spontaneously and in response to electrical field stimulation. Most of the cells in the side channel expressed a non-myocyte marker vimetin. Fluorescent activated cell sorting indicated significant enrichment in the side channel (p< 0.001) for non-myocytes. Original cell suspension had a bimodal cell size distribution with the peaks in the range from 7–9 μm and 15–17 μm. Upon cell sorting the distribution was Gaussian in both side channel and middle channel with the peaks in the range 7–9 μm and 9–11 μm respectively, indicating that the separation by size occurred.

Apheresis is a procedure used to fractionate whole blood into its individual components. Following fractionation, the desired component is isolated and the remaining blood in many cases is returned to the donor. Leukapheresis is one type of apheresis where leukocytes (white blood cells) are selectively removed. This procedure is commonly used for blood transfusions to remove donor leukocytes from being transferred to the recipient. Apheresis also has several therapeutic applications. In this manuscript we discuss the design, fabrication and testing of a continuous flow diffusive filter, fabricated using simple soft lithographic techniques for depletion of leukocytes. This device employs micro sieves that exploit the size and shape difference between the different cell types to obtain depletion of leukocytes from whole blood. Currently, conventional apheresis methods like centrifugation or fiber mesh filtration are commonly used. A theoretical model was developed to determine the optimal shape of the diffuser to ensure that the volumetric flow through individual sieve elements is equal. This device was designed to serve as a passive device that does not require any external manipulation. Results show that for the given device design, isolation of ∼50% of the inlet erythrocytes (red blood cells), along with depletion of >97% of the inlet leukocytes is possible at a flow rate of 5 µl min−1. Simple modifications to the geometry and dimensions of the sieves can be made to obtain isolation of plasma.