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Chih-Ming Ho

Publications and source records attributed to Chih-Ming Ho.

At least 19 recordsLinked to original sources

Evaluation of synthetic linear motor-molecule actuation energetics.

By applying atomic force microscope (AFM)-based force spectroscopy together with computational modeling in the form of molecular force-field simulations, we have determined quantitatively the actuation energetics of a synthetic motor-molecule. This multidisciplinary approach was performed on specifically designed, bistable, redox-controllable [2]rotaxanes to probe the steric and electrostatic interactions that dictate their mechanical switching at the single-molecule level. The fusion of experimental force spectroscopy and theoretical computational modeling has revealed that the repulsive electrostatic interaction, which is responsible for the molecular actuation, is as high as 65 kcal.mol(-1), a result that is supported by ab initio calculations.

Microscopy, Atomic Force↗

Nanomanufacturing and characterization modalities for bio-nano-informatics systems.

In the next decade or two, the feature size of microelectronic devices will continue to decrease and is eventually expected to reach fabrication and material limits. With the field of microelectronics rapidly approaching the end of its roadmap, the National Nanotechnology Initiative (NNI) was created for the purpose of creating new technologies and to maintain the momentum of continuous scientific and technological progress. Primarily, the fields of nanoscience and nanotechnology aim to synthesize, characterize, apply, and control macro functional molecules and consist of three areas. First, the area of bio-nanotechnologies concerns that of biological molecules such as DNA, the molecule that serves as the blueprint of all living organisms. Harnessing the intrinsic functionality of these nano-sized biological molecules, i.e., DNA/RNA and proteins, will yield enormous potential for a wide array of applications (biomedical, energy, sensing, etc.) Second, diminishing electronic device feature sizes has spurred the development of new techniques for nanoelectronics and has emerged as a critical area of research. Third, these macro functional molecules possess rich potential for various new nanomaterials that have applications in bio-nano and nanoelectronics industries. Given the range of devices and applications that may be generated and addressed, respectively, through the fruition of these areas, development of novel and advanced core characterization and nanomanufacturing technologies will serve as a requisite strategy toward the realization of the potential underlying nanotechnological development. As such, this review will address how these novel technologies will be used to achieve a true coalescence of nanoscience and nanotechnology. This, in turn, will ultimately benefit the human condition by using the building blocks and fundamental findings of nanoscience to develop systems based on the fusion of biology, nanotechnology, and informatics, with embedded intelligence and emergent behavior.

Computational Biology↗

Integrated human papillomavirus types 52 and 58 are infrequently found in cervical cancer, and high viral loads predict risk of cervical cancer.

OBJECTIVE: The aim of this prospective study was to analyze whether integration or high viral loads of human papillomavirus (HPV) is essential for malignant transformation of HPV types 52 and 58 as well as types 16 and 18. METHODS: Cervical swabs from 178 consecutive patients, including 81 with invasive cervical cancers and 97 with cervical intraepithelial neoplasias (CIN) II-III, were collected and examined to determine the physical status and viral load of HPV types 16, 18, 52 and 58 DNA using genechip and real-time PCR (polymerase chain reaction) analysis. RESULTS: In cervical cancer patients, the integrated form of HPV 52 and 58 DNA was found in 25.0% and 12.5% of swabs, respectively; while HPV16 and 18 DNA was found in 82.6% and 100% of swabs, respectively (P < 0.01, for pair-wise comparison of types 16, 18 versus types 52, 58). The viral loads reflected by the amount of E6 for HPV 16, 18, or 52 were significantly increased in invasive cervical cancer compared to CINII-III (P = 0.022 for type 16, P = 0.003 for type18, and P = 0.001 for type 52, respectively). Area under the receiver operating characteristic (ROC) curve for cervical cancer versus CIN II-III was 73.8%, 92.9%, and 88.5% for HPV 16, 18, and 52, respectively, indicating that real-time PCR had good diagnostic value in differentiating cervical cancer from CIN II-III. CONCLUSIONS: Infrequent integration of HPV 52 and 58 DNA in cervical cancer suggests that it is not prerequisite for progression to cervical cancer. High viral loads (E6) of HPV 16, 18, and 52 DNA may be predictive of the transition of CIN II-III to cervical cancer. Our results indicate that both viral DNA physical status and viral loads of HPV are important factors in the carcinogenesis of different HPV types.

DNA, Viral↗

Bubble dispenser in microfluidic devices.

This Brief Report presents experimental and computational results on bubble formation in microfluidic devices. Bubbles are generated at the right-angle intersection of four identical square microchannels. When the pressure gradient generated by the liquid flow dominates the pressure gradient generated by gas flow, the length of the produced confined bubbles follows a law based on the channel size and fluid volume fraction. This bubble production technique was used to produce monodisperse aqueous foam in two-dimensional and three-dimensional microchannels.

Computer Simulation↗

Detection of picomolar levels of interleukin-8 in human saliva by SPR.

Researchers at UCLA have discovered that the levels of interleukin-8 (IL-8) protein in the saliva of healthy individuals and patients with oropharyngeal squamous cell carcinoma (OSCC) are 30 pM and 86 pM, respectively. In this study, we present the development of the first immunoassay for the quantification of picomolar IL-8 concentrations in human saliva using Biacore surface plasmon resonance (SPR) in a microfluidic channel. A sandwich assay using two monoclonal antibodies, which recognize different epitopes on the antigen (IL-8), was used. Only 13 minutes were required to determine the quantity of pure IL-8 added to just 100 microL of either buffer or saliva-based samples. The limit of detection (LOD) of this immunoassay in buffer was 2.5 pM, and the precision of the response for each concentration was <3% of the coefficient of variation. When first analyzing the saliva supernatants, non-specific binding to the surface was observed. By adding carboxymethyl dextran sodium salt (10 mg mL(-1)) to compete with the surface dextran and primary antibody for non-specific interactions, the signal to noise ratio was greatly improved. The LOD of this immunoassay in saliva was 184 pM. A minimum concentration of 250 pM of exogenous IL-8 could then be consistently detected in a salivary environment. The precision of the response for each IL-8 concentration tested was <7% of the coefficient of variation. Diagnostic sensitivity for oral cancer can be achieved by pre-concentrating the saliva samples 10 fold prior to SPR analysis, making the target levels of IL-8 300 pM for healthy individuals and 860 pM for oral cancer patients.

Animals↗

Detection and quantitation of human papillomavirus type 16, 18 and 52 DNA in the peripheral blood of cervical cancer patients.

OBJECTIVE: To prospectively evaluate the feasibility of detecting human papillomavirus (HPV) type 16, 18 and 52 DNA in the peripheral blood of patients with cervical cancer using real-time polymerase chain reaction (PCR) and to determine its prognostic importance. METHODS: Blood and cervical swab specimens from 135 consecutive patients with 60 invasive cervical cancers, 10 microinvasions, 20 cervical intraepithelial neoplasias (CIN) III, 10 CIN II, 10 CIN I and 25 controls were collected and examined for HPV type 16, 18 and 52 DNA using real-time PCR to investigate the prevalence and viral load of HPV DNA at the time of diagnosis and during follow-up in patients with positive blood samples. RESULTS: Of the 60 patients with invasive cervical cancer, 27% had positive test results for HPV DNA in blood samples in contrast to 0% of patients with microinvasions, CIN III, CIN II, CIN I and normal controls. The DNA detection rates of viral subtypes in blood samples of cervical cancer patients were 5% for HPV-16, 16.7% for HPV-18, 8.3% for HPV-52, 1.7% for both HPV-16 and HPV-18 and 1.7% for both HPV-18 and HPV-52, while the detection rates in cervical swab specimens were 36.2% for HPV-16, 15.5% for HPV-18 and 17.2% for HPV-52. During follow-up, 8 of 10 cervical cancer patients with viral DNA detected in blood within 3 months after treatment had recurrence, and a high percentage (87.5%, 7/8) of this recurrence involved distant metastases. CONCLUSIONS: In this study, real-time PCR detected HPV-16, -18 or -52 DNA in the peripheral blood of more than one-fourth of invasive cervical cancer patients. The association between risk of cancer recurrence and the amount of viral DNA detected in blood among cervical cancer patients after treatment is intriguing and deserves further investigation.

Adult↗

Linear artificial molecular muscles.

Two switchable, palindromically constituted bistable [3]rotaxanes have been designed and synthesized with a pair of mechanically mobile rings encircling a single dumbbell. These designs are reminiscent of a "molecular muscle" for the purposes of amplifying and harnessing molecular mechanical motions. The location of the two cyclobis(paraquat-p-phenylene) (CBPQT(4+)) rings can be controlled to be on either tetrathiafulvalene (TTF) or naphthalene (NP) stations, either chemically ((1)H NMR spectroscopy) or electrochemically (cyclic voltammetry), such that switching of inter-ring distances from 4.2 to 1.4 nm mimics the contraction and extension of skeletal muscle, albeit on a shorter length scale. Fast scan-rate cyclic voltammetry at low temperatures reveals stepwise oxidations and movements of one-half of the [3]rotaxane and then of the other, a process that appears to be concerted at room temperature. The active form of the bistable [3]rotaxane bears disulfide tethers attached covalently to both of the CBPQT(4+) ring components for the purpose of its self-assembly onto a gold surface. An array of flexible microcantilever beams, each coated on one side with a monolayer of 6 billion of the active bistable [3]rotaxane molecules, undergoes controllable and reversible bending up and down when it is exposed to the synchronous addition of aqueous chemical oxidants and reductants. The beam bending is correlated with flexing of the surface-bound molecular muscles, whereas a monolayer of the dumbbell alone is inactive under the same conditions. This observation supports the hypothesis that the cumulative nanoscale movements within surface-bound "molecular muscles" can be harnessed to perform larger-scale mechanical work.

Biomimetic Materials↗

Single-molecule tracing on a fluidic microchip for quantitative detection of low-abundance nucleic acids.

Here, we report a method capable of quantitative detection of low-abundance DNA/RNA molecules by incorporating confocal fluorescence spectroscopy, molecular beacons, and a molecular-confinement microfluidic reactor. By using a combination of ac and dc fields via a trio of 3-D electrodes in the microreactor, we are able to precisely direct the transport of individual molecules to a minuscule laser-focused detection volume ( approximately 1 fL). A burst of fluorescence photons is detected whenever a molecular beacon-target hybrid flows through the detection region, and the amount of targets can be directly quantified according to the number of recorded single-molecule flow-through events. This assay consumes only attomoles of molecular probes and is able to quantitatively detect subpicomolar DNA targets. A measurement time of less than 2 min is sufficient to complete the detection.

DNA↗

Epidemiologic correlates of cervical human papillomavirus prevalence in women with abnormal Pap smear tests: a Taiwan Cooperative Oncology Group (TCOG) study.

To explore factors affecting human papillomavirus (HPV) prevalence in all grades of cervical neoplasia among Chinese women, 1,264 women with abnormal cervical cytology attending the gynaecologic clinics of 11 major medical centres in Taiwan. Patients were interviewed and underwent complete gynaecologic examination including colposcopy. Cervical scrapings were collected for HPV DNA detection by both Hybrid Capture-2 (high-risk probe) and L1 consensus PCR-reverse line blot. The prevalences of HPV in the four different diagnosis groups: (i) suspicious (n = 316), (ii) low-grade intraepithelial lesion (n = 474), (iii) high-grade intraepithelial lesion (n = 450), and (iv) cancer (n = 16), were 36.1%, 74.7%, 83.6%, and 100%, respectively. In the latter two groups, Patients less than 30 or 40 years old, respectively, tended to be infected more frequently with HPV than the older patients were. The main correlates of HPV prevalence were lifetime number of sex partners (odds ratio (OR) for two or more partners: 2.44; 95% CI, 1.44-4.15), vaginal douching after intercourse (OR for douching frequently: 1.44; 95% CI, 1.01-2.04), vitamin supplementation (OR for regular vitamin supplement: 0.71, 95% CI, 0.55-0.92), and performance of Pap smear tests (OR for never having a Pap smear performed: 2.22; 95% CI, 1.19-4.17). The risk for vaginal douching was augmented by the promiscuity of sex partners (OR of 3.19 (1.91-5.34)) and smoking (OR of 1.90 (1.15-3.13)), whereas vitamin supplementation reduced the odds ratio to 1.35 (0.85-2.15). The results of this study provide further evidence of the role of HPV in cervical carcinogenesis. The data also indicate the main areas of risk for the prevalence of HPV in cervical neoplasia in Chinese women living in Taiwan.

Adult↗

Cell relaxation after electrodeformation: effect of latrunculin A on cytoskeletal actin.

Precise measurement of the mechanical properties of a cell provides useful information about its structural organization and physiological state. It is interesting to understand the effect of individual components on the mechanical properties of the entire cell. In this study, we investigate the influence of the cytoskeletal actin on the viscoelastic properties of a cell. Actin-specific agents, including latrunculin A and jasplakinolide, are used to alter the organization of the cytoskeletal actin. Brassica oleracea protoplasts are treated with the drugs and deformed under an external electric potential. The relaxation processes of single protoplasts after electrodeformation are measured. The data are analyzed by a model-independent spectrum recovery algorithm. Two distinct characteristic time constants are obtained from the relaxation spectra. Treatment with latrunculin A increases both of the relaxation time constants. The longest relaxation times for control, latrunculin A treated, and jasplakinolide treated cells are determined to be 0.28, 1.0, and 0.21 s, respectively.

Actins↗

Prevalence of cervical human papillomavirus in Taiwanese women.

PURPOSE: To define the prevalence rate of cervical human papilloma virus (HPV) using DNA oligonucleotide microarray and its correlation with risk factors in Taiwanese women in metropolitan Taipei. METHODS: Thirteen hundred and twenty healthy women, aged 21 - 65 yr without history of cervical intraepithelial neoplasia (CIN) or carcinoma were included in this prospective study. Pap smear and HPV typing using oligonucleotide microarray were performed for each woman. They were given a standardized questionnaire to obtain information about the risk factors of cervical cancer in Taiwan. RESULTS: The overall HPV positivity was 19.85% and multiple infections were found in 35.84% of the infected group, 7.92% of the whole study population. The younger the subject, the higher was the infection rate and multiple infection rates. The most common HPV types were 16, 18, 58, 52, 51 and 56, which is different from the western world. The sensitivity of the HPV DNA chip in detecting CIN and cervical carcinoma is 97.06%, and 100% in detecting CIN 2 or more lesions. Risk factors for HPV infection include earlier coitarche (P < 0.01), multiple sexual partners (P < 0.05), history of sexually transmitted disease (P < 0.05), two or more vaginal deliveries (P < 0.05) and infrequent use of condoms (P < 0.05). The association between oral contraception or cigarette smoking and HPV infection could not be determined because few women smoke or used oral contraception. There was no relationship between induced abortion and HPV infection. CONCLUSIONS: About one-fifth of adult women in metropolitan Taipei were cervical HPV positive. The popular HPV types and the risk factors of HPV infection in metropolitan Taipei are not the same as those in the western world. The sensitivity of the HPV DNA chip in detecting cervical neoplasia is very high.

Adult↗

Electrokinetic bioprocessor for concentrating cells and molecules.

Bioprocessors for concentrating bioparticles, such as cells and molecules, are commonly needed in bioanalysis systems. In this microfluidic processor, a global flow field generated by ac electroosmosis transports the embedded particles to the regions near the electrode surface. The processor then utilizes electrophoretic and dielectrophoretic forces, which are effective in short range, to trap the target cells and molecules on the electrode surface. By optimizing the operating parameters, we have concentrated various biological objects in a large range of sizes, including Escherichia coli bacteria, lambda phage DNA, and single-stranded DNA fragments as small as 20 bases that have a radius of gyration of only 3 nm.

Bacteriophage lambda↗

Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma.

BACKGROUND: Since morbidity and mortality rates due to oral cavity and oropharyngeal squamous cell carcinoma (OSCC) have improved little in the past 30 years, early detection or prevention of this disease is likely to be most effective. Using laser-capture microdissection, we have identified the expression of 2 cellular genes that are uniquely associated with OSCC: interleukin (IL) 6 and IL-8. These cytokines may contribute to the pathogenesis of this disease, and have been linked with increased tumor growth and metastasis. OBJECTIVES: To investigate whether IL-6 and/or IL-8 could serve as informative biomarkers for OSCC in saliva and/or serum and to determine if there is a role for saliva as a diagnostic medium for OSCC. PATIENTS AND METHODS: Patients with newly diagnosed T1 or T2 oral cavity or oropharyngeal histologically confirmed squamous cell carcinoma were recruited for the study. Age and sex-matched disease-free subjects were used as controls. Using quantitative real-time polymerase chain reaction analysis and enzyme-linked immunosorbent assay, we respectively assessed the expression of IL-6 and IL-8 in serum (controls, n = 32; patients with OSCC, n = 19) and saliva (controls, n = 32; patients with OSCC, n = 32) at the messenger RNA (mRNA) and protein levels. MAIN OUTCOME MEASURES: Specificity and sensitivity of these biomarkers for OSCC and their predictive value. RESULTS: Interleukin 8 was detected at higher concentrations in saliva (P<.01) and IL-6 was detected at higher concentrations in serum of patients with OSCC (P<.01). We confirmed these results at both the mRNA and the protein levels, and the results were concordant. The concentration of IL-8 in saliva and IL-6 in serum did not appear to be associated with sex, age, or alcohol or tobacco use (P>.75). Using statistical analysis, we were able to determine the threshold value, sensitivity, and specificity of each biomarker, as well as a combination of biomarkers, for detecting OSCC. CONCLUSIONS: Our findings indicate that IL-8 in saliva and IL-6 in serum hold promise as biomarkers for OSCC. A saliva-based test could be a cost-effective adjunctive tool in the diagnosis and follow-up of patients with OSCC.

Adult↗

Multivariate analysis of the prognostic factors and outcomes in early cervical cancer patients undergoing radical hysterectomy.

OBJECTIVE: This study was performed to identify pathologic and clinical risk factors that best predicted 5-year recurrence-free survival (RFS) among patients with early-stage cervical carcinoma, treated by radical hysterectomy and pelvic lymphadenectomy. METHODS: The records of 197 patients with early-stage invasive cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy from 1990 to 1999 were retrospectively reviewed. Clinical and pathologic variables including age, tumor size (TS), clinical stage, depth of invasion (DI), lymphovascular space involvement (LVSI), cell type, tumor grade, lymph node metastases (LNM), parametrial invasion, surgical margin involvement, and pattern of adjuvant therapy were analyzed using univariate and multivariate methods to define those variables that best predicted RFS. RESULTS: Outer 1/3 invasion, LVSI, and LNM were identified as independent poor prognostic factors, which were used to define three prognostic groups: patients (n = 104) with good prognoses (LVSI (-) and LNM (-)), patients (n = 46) with intermediate prognoses (either LVSI (+) without outer 1/3 invasion or LNM (+) without LVSI), and patients (n = 47) with poor prognoses (LVSI (+) patients with outer 1/3 invasion). The estimated 3-year RFS for patients with LVSI and deeply invasive tumors regardless of nodal status and/or nodal metastases receiving adjuvant CT + RT was significantly greater than that for patients who received only adjuvant radiotherapy (80% vs. 49%, P = 0.048 in the group of patients with LVSI and deeply invasive tumors with positive nodes and without positive nodes; 87% vs. 36%, P = 0.013 in the group of patients with LVSI and deeply invasive tumors with positive nodes only). CONCLUSIONS: The multivariate analysis and prognostic grouping system maximally separated patients with early-stage invasive cervical carcinoma into groups with good, intermediate, or poor prognoses, with 3-year RFSs of 90%, 82%, 67%; and 5-year RFSs of 89%, 69%, 43%, respectively. CT + RT played a role in improving RFS among patients with LVSI and deeply invasive tumors and poor prognoses.

Adult↗

Pure-type clear cell carcinoma of the ovary as a distinct histological type and improved survival in patients treated with paclitaxel-platinum-based chemotherapy in pure-type advanced disease.

OBJECTIVE: The aim was to compare survival in pure and mixed-type advanced clear cell ovarian carcinoma and to determine the benefits among patients with pure advanced clear cell ovarian carcinoma treated in paclitaxel-platinum-based chemotherapy in comparison with those treated in conventional platinum-based chemotherapy after primary surgery. METHODS: Between 1994 and 2001, 31 women with stage III and IV pure clear cell ovarian carcinoma and nine patients with stage III and IV mixed-type clear cell carcinoma were identified from the tumor registry of six institutions. All patients underwent cytoreductive surgery followed by conventional platinum-based chemotherapy or paclitaxel and platinum-based chemotherapy. RESULTS: The median survival of women with pure clear cell carcinoma was 11 months, compared to 48+ months for those with mixed-type clear cell carcinoma (P = 0.003). Overall, for women with pure clear cell carcinoma, 35% had clinically complete responses to chemotherapy. For women with pure clear cell carcinoma treated with paclitaxel-platinum-based chemotherapy, the median survival was significantly longer than for those treated with conventional platinum-based chemotherapy (16.26 vs. 10.75 months, P = 0.045; with optimal cytoreduction, 40.95 vs. 9.02 months, P = 0.028). Univariate analysis showed paclitaxel-platinum-based treatment was the only favorable prognostic factor for women with advanced pure clear cell ovarian carcinoma (P = 0.05). CONCLUSIONS: Patients with advanced pure clear cell ovarian carcinoma have poorer prognoses than those with the mixed type. Paclitaxel-platinum-based chemotherapy improved survival among our patients with advanced pure clear cell carcinoma, especially for those with optimal cytoreduction.

Adenocarcinoma, Clear Cell↗

Micro sensors: linking real-time oscillatory shear stress with vascular inflammatory responses.

The important interplay between blood circulation and vascular cell behavior warrants the development of highly sensitive but small sensing systems. The emerging micro electro mechanical systems (MEMS) technology, thus, provides the high spatiotemporal resolution to link biomechanical forces on the microscale with large-scale physiology. We fabricated MEMS sensors, comparable to the endothelial cells (ECs) in size, to link real-time shear stress with monocyte/EC interactions in an oscillatory flow environment, simulating the moving and unsteady separation point at arterial bifurcations. In response to oscillatory shear stress (tau) at +/- 2.6 dyn/cm2, time-averaged shear stress (tauave) = 0 at 0.5 Hz, individual monocytes displayed unique to-and-fro trajectories, undergoing rolling, binding, and dissociation with other monocyte, followed by solid adhesion on EC. Incorporating with cell-tracking velocimetry, we visualized that these real-time events occurred over a dynamic range of oscillating shear stress between +/- 2.6 dyn/cm2 and Reynolds number between 0 and 22.2 in the presence of activated adhesion molecule and chemokine mRNA expression.

Animals↗

Evaluation of complete surgical staging with pelvic and para-aortic lymphadenectomy and paclitaxel plus carboplatin chemotherapy for improvement of survival in stage I ovarian clear cell carcinoma.

OBJECTIVE: The aim was to determine the benefits of lymphadenectomy and paclitaxel plus carboplatin chemotherapy for stage I ovarian clear cell carcinoma (defined as intra-abdominal disease confined to the ovaries). METHODS: Twenty patients with stage I pure clear cell carcinoma of the ovary diagnosed between 1991 and 2001 were divided into two groups: Group A (12 patients, 1997-2001) underwent complete surgical staging including bilateral salpingo-oophorectomy, hysterectomy, omentectomy, and pelvic and para-aortic lymphadenectomy, followed by paclitaxel and carboplatin chemotherapy. Group B (8 patients, 1991-1996) underwent bilateral salpingo-oophorectomy, hysterectomy, and omentectomy without lymphadenectomy, followed by cisplatin-based chemotherapy. The survival of the two groups was compared. The clinical characteristics of the two groups were evaluated for age distribution, grade, substage, preoperative CA-125, presence or absence of endometriosis, and maximal tumor diameter. RESULTS: The estimated 4-year survival rate was 76.9%. The clinical characteristics of the two groups were similar, except for lymphadenectomy and regimen of chemotherapy. With a median follow-up of 36 months (range: 11-130 months), one of 12 patients in Group A had recurrence in comparison with 6 of 8 patients in Group B (P = 0.004). The estimated 3-year recurrence-free survival and 4-year overall survival for Group A was significantly greater than that for Group B (91.7 vs 33.3%, P = 0.014; 100 vs 50%, P = 0.014). Median time to recurrence was 8 months. CONCLUSIONS: Complete surgical staging, including pelvic and para-aortic lymphadenectomy and paclitaxel plus carboplatin chemotherapy, appeared to be capable of improving survival of patients with stage I ovarian clear cell carcinoma.

Adenocarcinoma, Clear Cell↗

Monocyte recruitment to endothelial cells in response to oscillatory shear stress.

Leukocyte recruitment to endothelial cells is a critical event in inflammatory responses. The spatial, temporal gradients of shear stress, topology, and outcome of cellular interactions that underlie these responses have so far been inferred from static imaging of tissue sections or studies of statically cultured cells. In this report, we developed micro-electromechanical systems (MEMS) sensors, comparable to a single endothelial cell (EC) in size, to link real-time shear stress with monocyte/EC binding kinetics in a complex flow environment, simulating the moving and unsteady separation point at the arterial bifurcation with high spatial and temporal resolution. In response to oscillatory shear stress (tau) at +/- 2.6 dyn/cm2 at a time-averaged shear stress (tau(ave))=0 and 0.5 Hz, individual monocytes displayed unique to-and-fro trajectories undergoing rolling, binding, and dissociation with other monocyte, followed by solid adhesion on EC. Our study quantified individual monocyte/EC binding kinetics in terms of displacement and velocity profiles. Oscillatory flow induces up-regulation of adhesion molecules and cytokines to mediate monocyte/EC interactions over a dynamic range of shear stress +/- 2.6 dyn/cm2 (P=0.50, n=10).

Biosensing Techniques↗