Increased p-cresyl sulfate level is independently associated with poor outcomes in patients with heart failure.

Amino acid-derived metabolites, including protein-bound uremic toxins, may have prognostic value for patients with heart failure (HF). The aim of this study was to investigate whether p-cresyl sulfate (PCS), indoxyl sulfate (IS), and arginine metabolites provided prognostic values in addition to the traditional biomarker, B-type natriuretic peptide (BNP), in patients with HF. Chromatography mass spectrometry was performed to measure tyrosine, tryptophan, arginine, PCS, IS, and asymmetric (ADMA) and symmetric dimethylarginine (SDMA) in the plasma from 51 normal controls and 136 HF patients. Compared to the normal controls, PCS levels significantly increased in HF patients (p = 0.003). During the follow-up (2.3 ± 1.1 years), 35 (25.7 %) patients experienced a composite event of death or HF-related re-hospitalization. In univariable analysis, PCS, estimated glomerular filtration rate (eGFR), BNP, DMA/arginine ratio, and ADMA/arginine ratio were associated with a higher rate of composite events. In the multivariable analysis, PCS was the only independent predictor of composite events [hazard ratio (HR) 1.06 (per 10 µM), 95 % confidence interval (CI) 1.01-1.11, p = 0.02]. Kaplan-Meier curves showed that a PCS level of ≥50 µM was significantly associated with a higher composite event rate than those with a PCS level of <50 µM (Log rank = 5.11, p = 0.024; HR 2.13, 95 % CI 1.09-4.16, p = 0.02). In conclusion, among protein-bound uremic toxins, eGFR, and DMA metabolites, increased PCS is the only independent predictor of HF-related events in patients with HF. A combination of PCS and BNP should better risk-stratify patients with HF.

[Action Plan to Improve the Utilization of Stationary Bikes in a Health Promotion Exercise Program].

BACKGROUND & PROBLEM: Research has shown that exercise helps reduce the risk and the severity of metabolic syndrome. Since 2009, KMHK hospital has implemented a primary-prevention health promotion program that targets individuals who are at elevated risk of metabolic syndrome. The program engages participants in an exercise protocol that asks them to exercise regularly on a stationary bike three times a week for six months. The utilization rate of the stationary bikes averaged 75% in 2010, but reduced to 34.7% in 2011, with an average withdrawal rate of 24.3%. Therefore, an action team was assembled in order to enhance the effectiveness of the program. PURPOSE: This project used two primary strategies to increase the utilization of stationary bikes. These strategies included: increasing referrals and decreasing withdrawals. METHODS: Surveys of participants who, respectfully, failed to complete and successfully completed the exercise protocol were conducted to identify the factors associated with non-completion / completion. The enrollment policies, the equipment, and the environment were inspected comprehensively. After identifying the causes and effects, several interventions were implemented. These interventions included: installing insulation curtains to block direct sunlight, upgrading the stationary bikes to newer models, creating an environment more conducive to exercise, promoting the referral policies, marketing the health promotion program, and securing family support. RESULTS: After three months, the utilization rate of stationary bikes increased to 77.8%, representing an improvement rate of 124%. Furthermore, the number of case referrals significantly increased and the withdrawal rate decreased to 4.8%. Finally, longer-term follow up indicates that the utilization rate and the withdrawal rate have continued to improve. CONCLUSIONS: The program implemented in the present study successfully enrolled more participants in the exercise protocol, as evidenced by the increased utilization of stationary bikes and by the lower withdrawal rate. Meanwhile, the risk factors for metabolic syndrome among the participants improved dramatically, which in turn achieved the goal of primary prevention and demonstrated program effectiveness.

Immunomagnetic nanoscreening of circulating tumor cells with a motion controlled microfluidic system.

Combining the power of immunomagnetic assay and microfluidic microchip operations, we successfully detected rare CTCs from clinical blood samples. The microfluidic system is operated in a flip-flop mode, where a computer-controlled rotational holder with an array of microfluidic chips inverts the microchannels. We have demonstrated both theoretically and experimentally that the direction of red blood cell (RBC) sedimentation with regards to the magnetic force required for cell separation is important for capture efficiency, throughput, and purity. The flip-flop operation reduces the stagnation of RBCs and non-specific binding on the capture surface by alternating the direction of the magnetic field with respect to gravity. The developed immunomagnetic microchip-based screening system exhibits high capture rates (more than 90%) for SkBr3, PC3, and Colo205 cell lines in spiked screening experiments and successfully isolates CTCs from patient blood samples. The proposed motion controlled microchip-based immunomagnetic system shows great promise as a clinical tool for cancer diagnosis and prognosis.

Computational analysis of microfluidic immunomagnetic rare cell separation from a particulate blood flow.

We describe a computational analysis method to evaluate the efficacy of immunomagnetic rare cell separation from non-Newtonian particulate blood flow. The core procedure proposed here is calculation of local viscosity distributions induced by red blood cell (RBC) sedimentation. Numerical calculation methods have previously been introduced to simulate particulate behavior of individual RBCs. However, due to the limitation of the computational power, those studies are typically capable of calculating only a very small number (less than 100) of RBCs and are not suitable to analyze many practical separation methods for rare cells such as circulating tumor cells (CTCs). We introduce a sedimentation and viscosity model based on our experimental measurements. The computational field is divided into small unit control volumes, where the local viscosity distribution is dynamically calculated based on the experimentally found sedimentation model. For analysis of rare cell separation, the local viscosity distribution is calculated as a function of the volume RBC rate. The direction of gravity has an important role in such a sedimentation-involved cell separation system. We evaluated the separation efficacy with multiple design parameters including the channel design, channel operational orientations (inverted and upright), and flow rates. The results showed excellent agreement with real experiments to demonstrate the effectiveness of our computational analytical method. We demonstrated higher capture efficiency with the inverted microchannel configuration.We conclude that proper direction of blood sedimentation significantly enhances separation efficiency in microfluidic devices.

Non-invasive cardiac index monitoring during cardiopulmonary functional testing provides additional prognostic value in patients after acute heart failure.

The prognostic value of parameters derived from a cardiopulmonary exercise test (CPET) is well established in patients stabilized after acute heart failure (HF). Under multidisciplinary disease management, this study sought to test whether noninvasive cardiac output (CO) monitoring (NICOM) during the CPET provides additional prognostic value. In total, 131 patients stabilized after acute HF agreed to undergo the CPET with NICOM. Outcome follow-up focused on composite events of death and HF-related rehospitalization. Patients with a peak cardiac index (CI) of ≤ 4.5 L/minute/ m(2) (n = 32), compared to those with a peak CI of > 4.5 L/minute/m(2) (n = 99), had higher incidences of diabetes mellitus (DM) and hypertension, but had lower hemoglobin levels, estimated glomerular filtration rates (eGFR), oxygen uptake efficiency slope (OUES), and peak oxygen uptake (VO(2)). During the 1.2 ± 0.7 years of follow-up, there were 8 (6.1%) deaths, and 16 (12.2%) HF-related rehospitalizations. In a Cox univariable analysis, a lower event-free survival was associated with a history of DM, a higher Ve/VCO(2) slope, lower peak VCO(2) and eGFR, and a peak CI of ≤ 4.5 L/minute/ m(2) (P < 0.05). The Cox multivariable analysis showed that the Ve/VCO(2) slope (hazard ratio (HR) = 1.08, 95% confidence interval (CI): 1.01~1.16, P = 0.02) and peak CI of ≤ 4.5 L/minute/m(2 )(HR = 3.26, 95% CI: 1.18~9.01, P = 0.02) were significant independent predictors. In conclusion, NICOM during the CPET was demonstrated to provide prognostic information in addition to traditional risk factors, biomarkers, and other well-established CPET parameters.

Edema index-guided disease management improves 6-month outcomes of patients with acute heart failure.

The efficacy of heart failure (HF) management programs is compromised by the challenge of early identification of patients at imminent risk. Segmental multifrequency bioelectrical impedance analysis can generate an "edema index" (EI) as a surrogate for the body fluid status. In this study, we tested whether integration of EI-guided management improved the 6-month outcomes of HF patients under multidisciplinary care. In total, 159 patients with acute HF were randomized into control, case management (CM), and EI-guided CM (EI) groups (n = 53 in each group). In the EI group, a management algorithm was designed based on the measured EI. The analyzed endpoints included HF-related and all cause-related events during the 6-month follow-up period. In the 6 months, there were 11 (6.9%) deaths, 19 (11.9%) HF-related rehospitalizations, and 45 (28.3%) all-cause-related rehospitalizations. Compared to the control (26.4%) and CM groups (15.1%), the EI group had a lower rate of HF-related death and rehospitalization (3.8%, P = 0.004). Multivariate analysis revealed that EI-guided management was an independent predictor of a lower HF-related event rate (hazard ratio = 0.15, 95%CI = 0.03~0.66, P = 0.012). Patients with a higher pre-discharge EI were older, had lower blood albumin and hemoglobin levels, and had a higher functional class and incidences of diabetes mellitus and chronic kidney disease. An increase in the pre-discharge EI by 0.001 increased the HF-related event rate by 6% (P = 0.002). Use of EI-guided management lowered this risk (P = 0.03). In conclusion, an EI-based HF management program demonstrated an event-lowering effect superior to traditional nurse-led multidisciplinary care in 6 months after an acute HF episode.

Plasmonic nanograting tip design for high power throughput near-field scanning aperture probe.

We design nanogratings consisting of concentric plasmonic resonance grooves on the metallic sidewalls of near-field scanning probe aperture to increase the power throughput without losing the imaging resolution. Nanograting tip design involves choosing the proper pitch length and the cut location of grooves. Four different nanograting designs are evaluated, as compared with standard single aperture pyramidal near-field scanning probe without grating patterns. We show that, by adding nano-grooves at the location of electromagnetic field intensity-maximum along interface and with the pitch period matching the surface plasmon wavelength, the power throughput can be greatly increased by at least a factor of 530 at 405nm UV wavelength with 100nm diameter aperture probe.

[Perceived barriers to taking a Pap smear: predictors in immigrant women].

BACKGROUND: New immigrant women in Taiwan are believed to generally perceive that "no illness" infers good health. Because medical inspection induces feelings of discomfit and due to language barriers, limited/no insurance coverage and more limited access to medical resources, understanding better the motivation of immigrant women to take Pap smears, the actual examination rate and key factors that influence willingness is important. Coverage of this issue, however, is extremely limited in domestic research. PURPOSE: This study aimed to investigate: (i) The Pap smear screening rate amongst immigrant women; (ii) Immigrant women's perception of cervical cancer susceptibility and severity as well as cues to action and perceived barriers to taking a Pap smear; and (iii) Predictors of perceived barriers to taking Pap smears in this target population. METHODS: Using a cross-sectional descriptive correlation study design, 100 immigrant women were recruited from the outpatient clinic and inpatient wards of a regional teaching hospital in Kaohsiung. Structured questionnaires included a demographic survey, scales of susceptibility and cervical cancer severity, scales of cues to action and barriers to receiving a Pap smear. RESULTS: One-quarter (25%) of the surveyed population had never taken a Pap smear. Immigrant women perceived their knowledge somewhat insufficient with regard to cervical cancer susceptibility and severity. Level of education, previous Pap smear experience, and number of children represented significant predictors of perceived barriers in taking Pap smears, accounting collectively for 26.1% perceived variance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Findings suggest that appropriate interventions should be targeted on the general healthcare population as well as tailored to specific immigrant national populations in order to improve Pap smear screening rates amongst immigrant women.

Emotional distress and quality of life during folinic acid, fluorouracil, and oxaliplatin in colorectal cancer patients with and without chemotherapy-induced peripheral neuropathy: A cross-sectional study.

When the 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy regimen is used to treat colorectal cancer (CRC), chemotherapy-induced peripheral neuropathy (CIPN) caused by oxaliplatin can substantially affect quality of life (QOL) in the CRC patients. This study compared emotional distress and QOL during FOLFOX in CRC patients with and without CIPN symptoms.This cross-sectional, descriptive, and comparative study recruited 68 CRC patients receiving FOLFOX at a local teaching hospital and at a medical center in southern Taiwan. Self-reported structured questionnaires (oxaliplatin-associated neuropathy questionnaire, profile of mood states short form, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30, version 3.0) were used for 1-time data collection. The Chi-square test, Fisher exact test, and Mann-Whitney U test were used to analyze data, and a P-value < .05 was considered statistically significant.The CIPN group had 45 (66.2%) patients, and the non-CIPN group had 23 (33.8%) patients. The 5 most common symptoms were coldness-related burning sensation or discomfort in the upper limbs, numbness in the upper limbs, tingling in the upper limbs, impairment of vision, and discomfort in the throat. The CIPN group had more females (P = .013), a more advanced stage of CRC (P = .04) and a higher chemotherapy dosage (P = .006). The 2 groups did not significantly differ in anxiety (P = .065) or depression (P = .135). Compared to the non-CIPN group, the CIPN group had significantly lower functioning (P = .001) and global health status (P < .001) and significantly more symptoms (P < .001).The CIPN group had significantly lower QOL compared to the non-CIPN group. However, the CIPN group did not have lower emotional distress compared to the non-CIPN group. The results of this study demonstrate the need for in-service courses specifically designed to train health professionals in assessing and managing CIPN symptoms to improve QOL in CRC patients receiving FOLFOX.

Inkjet-Print Micromagnet Array on Glass Slides for Immunomagnetic Enrichment of Circulating Tumor Cells.

We report an inkjet-printed microscale magnetic structure that can be integrated on regular glass slides for the immunomagnetic screening of rare circulating tumor cells (CTCs). CTCs detach from the primary tumor site, circulate with the bloodstream, and initiate the cancer metastasis process. Therefore, a liquid biopsy in the form of capturing and analyzing CTCs may provide key information for cancer prognosis and diagnosis. Inkjet printing technology provides a non-contact, layer-by-layer and mask-less approach to deposit defined magnetic patterns on an arbitrary substrate. Such thin film patterns, when placed in an external magnetic field, significantly enhance the attractive force in the near-field close to the CTCs to facilitate the separation. We demonstrated the efficacy of the inkjet-print micromagnet array integrated immunomagnetic assay in separating COLO205 (human colorectal cancer cell line) from whole blood samples. The micromagnets increased the capture efficiency by 26% compared with using plain glass slide as the substrate.

Microscale magnetic field modulation for enhanced capture and distribution of rare circulating tumor cells.

Immunomagnetic assay combines the powers of the magnetic separation and biomarker recognition and has been an effective tool to perform rare Circulating Tumor Cells detection. Key factors associated with immunomagnetic assay include the capture rate, which indicates the sensitivity of the system, and distributions of target cells after capture, which impact the cell integrity and other biological properties that are critical to downstream analyses. Here we present a theoretical framework and technical approach to implement a microscale magnetic immunoassay through modulating local magnetic field towards enhanced capture and distribution of rare cancer cells. Through the design of a two-dimensional micromagnet array, we characterize the magnetic field generation and quantify the impact of the micromagnets on rare cell separation. Good agreement is achieved between the theory and experiments using a human colon cancer cell line (COLO205) as the capture targets.

Screening and Molecular Analysis of Single Circulating Tumor Cells Using Micromagnet Array.

Immunomagnetic assay has been developed to detect rare circulating tumor cells (CTCs), which shows clinical significance in cancer diagnosis and prognosis. The generation and fine-tuning of the magnetic field play essential roles in such assay toward effective single-cell-based analyses of target cells. However, the current assay has a limited range of field gradient, potentially leading to aggregation of cells and nanoparticles. Consequently, quenching of the fluorescence signal and mechanical damage to the cells may occur, which lower the system sensitivity and specificity. We develop a micromagnet-integrated microfluidic system for enhanced CTC detection. The ferromagnetic micromagnets, after being magnetized, generate localized magnetic field up to 8-fold stronger than that without the micromagnets, and strengthen the interactions between CTCs and the magnetic field. The system is demonstrated with four cancer cell lines with over 97% capture rate, as well as with clinical samples from breast, prostate, lung, and colorectal cancer patients. The system captures target CTCs from patient blood samples on a standard glass slide that can be examined using the fluorescence in-situ hybridization method for the single-cell profiling. All cells showed clear hybridization signals, indicating the efficacy of the compact system in providing retrievable cells for molecular studies.

Flux or speed? Examining speckle contrast imaging of vascular flows.

Speckle contrast imaging enables rapid mapping of relative blood flow distributions using camera detection of back-scattered laser light. However, speckle derived flow measures deviate from direct measurements of erythrocyte speeds by 47 ± 15% (n = 13 mice) in vessels of various calibers. Alternatively, deviations with estimates of volumetric flux are on average 91 ± 43%. We highlight and attempt to alleviate this discrepancy by accounting for the effects of multiple dynamic scattering with speckle imaging of microfluidic channels of varying sizes and then with red blood cell (RBC) tracking correlated speckle imaging of vascular flows in the cerebral cortex. By revisiting the governing dynamic light scattering models, we test the ability to predict the degree of multiple dynamic scattering across vessels in order to correct for the observed discrepancies between relative RBC speeds and multi-exposure speckle imaging estimates of inverse correlation times. The analysis reveals that traditional speckle contrast imagery of vascular flows is neither a measure of volumetric flux nor particle speed, but rather the product of speed and vessel diameter. The corrected speckle estimates of the relative RBC speeds have an average 10 ± 3% deviation in vivo with those obtained from RBC tracking.

An Immunofluorescence-Assisted Microfluidic Single Cell Quantitative Reverse Transcription Polymerase Chain Reaction Analysis of Tumour Cells Separated from Blood.

Circulating tumour cells (CTCs) are important indicators of metastatic cancer and may provide critical information for individualized treatment. As CTCs are usually very rare, the techniques to obtain information from very small numbers of cells are crucial. Here, we propose a method to perform a single cell quantitative reverse transcription polymerase chain reaction (qPCR) analysis of rare tumour cells. We utilized a microfluidic immunomagnetic assay to separate cancer cells from blood. A combination of detailed immunofluorescence and laser microdissection enabled the precise selection of individual cells. Cancer cells that were spiked into blood were successfully separated and picked up for a single cell PCR analysis. The breast cancer cell lines MCF7, SKBR3 and MDAMB231 were tested with 10 different genes. The result of the single cell analysis matched the results from a few thousand cells. Some markers (e.g., ER, HER2) that are commonly used for cancer identification showed relatively large deviations in expression levels. However, others (e.g., GRB7) showed deviations that are small enough to supplement single cell disease profiling.

Effect of multidisciplinary disease management for hospitalized heart failure under a national health insurance programme.

AIM: Multidisciplinary disease management programmes (MDPs) for heart failure have been shown to be effective in Western countries. However, it is not known whether they improve outcomes in a high population density country with a national health insurance programme. METHODS: In total, 349 patients hospitalized because of heart failure were randomized into control and MDP groups. All-cause death and re-hospitalization related to heart failure were analyzed. The median follow-up period was approximately 2 years. RESULTS: Mean patient age was 60 years; 31% were women; and 50% of patients had coronary artery disease. MDP was associated with fewer all-cause deaths [hazard ratio (HR) = 0.49, 95% confidence interval (CI) = 0.27-0.91, P = 0.02] and heart failure-related re-hospitalizations (HR = 0.44, 95% CI = 0.25-0.77, P = 0.004). MDP was still associated with better outcomes for all-cause death (HR = 0.53, 95% CI = 0.29-0.98, P = 0.04) and heart failure-related re-hospitalization (HR = 0.46, 95% CI = 0.26-0.81, P = 0.007), after adjusting for age, diuretics, diabetes mellitus, chronic kidney disease, hypertension, sodium, and albumin. However, MDPs' effect on all-cause mortality and heart failure-related re-hospitalization was significantly attenuated after adjusting for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers or ß-blockers. A stratified analysis showed that MDP combined with guideline-based medication had synergistic effects. CONCLUSIONS: MDP is effective in lowering all-cause mortality and re-hospitalization rates related to heart failure under a national health insurance programme. MDP synergistically improves the effectiveness of guidelines-based medications for heart failure.

Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics.

BACKGROUND: Identification of novel biomarkers is needed to improve the diagnosis and prognosis of heart failure (HF). Metabolic disturbance is remarkable in patients with HF. OBJECTIVES: This study sought to assess the diagnostic and prognostic values of metabolomics in HF. METHODS: Mass spectrometry-based profiling of plasma metabolites was performed in 515 participants; the discovery phase study enrolled 51 normal control subjects and 183 HF patients, and the validation study enrolled 63 control subjects and 218 patients with stage C HF. Another independent group of 32 patients with stage C HF who recovered to New York Heart Association functional class I at 6 and 12 months was profiled as the "recovery" group. RESULTS: A panel of metabolites, including histidine, phenylalanine, spermidine, and phosphatidylcholine C34:4, has a diagnostic value similar to B-type natriuretic peptide (BNP). In the recovery group, the values of this panel significantly improved at 6 and 12 months. To evaluate the prognostic values, events were defined as the combined endpoints of death or HF-related re-hospitalization. A metabolite panel, which consisted of the asymmetric methylarginine/arginine ratio, butyrylcarnitine, spermidine, and the total amount of essential amino acids, provided significant prognostic values (p < 0.0001) independent of BNP and traditional risk factors. The prognostic value of the metabolite panel was better than that of BNP (area under the curve of 0.85 vs. 0.74 for BNP) and Kaplan-Meier curves (log rank: 17.5 vs. 9.95). These findings were corroborated in the validation study. CONCLUSIONS: Metabolomics demonstrate powerful diagnostic value in estimating HF-related metabolic disturbance. The profile of metabolites provides better prognostic value versus conventional biomarkers.

Multiscale immunomagnetic enrichment of circulating tumor cells: from tubes to microchips.

We review the rare cancer cell sorting technologies, with a focus on multiscale immunomagnetic approaches. Starting from the conventional magnetic activated cell sorting system, we derive the scaling laws of immunomagnetic assay and justify the recent trend of using downscaled systems for CTC studies. Furthermore, we introduce recent work on combining the immunomagnetic assay with microfluidic technology for enhanced separation. We summarize different types of in-channel micro-magnetic structures that can further increase the local magnetic field without lowering the system throughput. Related design concepts, principles, and microfabrication techniques are presented and evaluated.

A correlational study of illness knowledge, self-care behaviors, and quality of life in elderly patients with heart failure.

BACKGROUND: Patients with heart failure experience adverse physical symptoms that affect quality of life. The number of patients with heart failure in Taiwan has been growing in recent years. PURPOSE: This article examines correlations among illness knowledge, self-care behaviors, and quality of life in elderly patients with heart failure. METHODS: A cross-sectional research design using three questionnaires was adopted. The study was undertaken in an outpatient department of a teaching hospital in Taiwan from January to June 2008. Potential participants aged 65 years or older were selected by a physician based on several diagnostic findings of heart failure that included an International Classification of Diseases' code 4280 or 4289. Patients who were bedridden or had a prognosis of less than 6 months were excluded from consideration. RESULTS: One hundred forty-one patients with heart failure were recruited. Most participants were men (51.8%), older adults (49.6% older than 71 years old), and either educated to an elementary school level or illiterate (69.5%) and have New York Heart Association class II (61.0%). Participants had an average left ventricular ejection fraction of 41.1%. The illness knowledge of participants was poor (accuracy rate: 29.3%), and most were unaware of the significance of self-care. Illness knowledge correlated with both self-care behaviors (r = -.42, p < .01) and quality of life (r = -.22, p < .01). Illness knowledge and age were identified as significant correlated factors of self-care behaviors (R = .22); and functional class, living independently, and age were identified as significant correlated factors of quality of life (R = .41). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Participants in this study with higher self-reported self-care behaviors and quality of life were younger in age and had better illness knowledge. Furthermore, physical function and independence in daily living significantly affected quality of life. Care for patients with heart failure, particularly older adults, should focus on teaching these patients about heart failure illness and symptom management. Assisting elderly patients with heart failure to promote and maintain physical functions to handle activities of daily living independently is critical to improving patient quality of life.

Point-of-care technologies for molecular diagnostics using a drop of blood.

Molecular diagnostics is crucial for prevention, identification, and treatment of disease. Traditional technologies for molecular diagnostics using blood are limited to laboratory use because they rely on sample purification and sophisticated instruments, are labor and time intensive, expensive, and require highly trained operators. This review discusses the frontiers of point-of-care (POC) diagnostic technologies using a drop of blood obtained from a finger prick. These technologies, including emerging biotechnologies, nanotechnologies, and microfluidics, hold the potential for rapid, accurate, and inexpensive disease diagnostics.

Versatile immunomagnetic nanocarrier platform for capturing cancer cells.

Sensitive and quantitative assessment of changes in circulating tumor cells (CTCs) can help in cancer prognosis and in the evaluation of therapeutics efficacy. However, extremely low occurrence of CTCs in the peripheral blood (approximately one CTC per billion blood cells) and potential changes in molecular biomarkers during the process of epithelial to mesenchymal transition create technical hurdles to the enrichment and enumeration of CTCs. Recently, efforts have been directed toward development of antibody-capture assays based on the expression of the common biomarker-the epithelial cell adhesion molecule (EpCAM) of epithelium-derived cancer cells. Despite some promising results, the assays relying on EpCAM capture have shown inconsistent sensitivity in clinical settings and often fail to detect CTCs in patients with metastatic cancer. We have addressed this problem by the development of an assay based on hybrid magnetic/plasmonic nanocarriers and a microfluidic channel. In this assay, cancer cells are specifically targeted by antibody-conjugated magnetic nanocarriers and are separated from normal blood cells by a magnetic force in a microfluidic chamber. Subsequently, immunofluorescence staining is used to differentiate CTCs from normal blood cells. We demonstrated in cell models of colon, breast, and skin cancers that this platform can be easily adapted to a variety of biomarkers, targeting both surface receptor molecules and intracellular biomarkers of epithelial-derived cancer cells. Experiments in whole blood showed capture efficiency greater than 90% when two cancer biomarkers are used for cell capture. Thus, the combination of immunotargeted magnetic nanocarriers with microfluidics provides an important platform that can improve the effectiveness of current CTC assays by overcoming the problem of heterogeneity of tumor cells in the circulation.