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Biomedical subjects

Wendy Franks

Publications and source records attributed to Wendy Franks.

9 recordsLinked to original sources

Characterization of a microfluidic dispensing system for localised stimulation of cellular networks.

We present a 3-D microfluidic device designed for localized drug delivery to cellular networks. The device features a flow cell comprising a main channel for nutrient delivery as well as multiple channels for drug delivery. This device is one key component of a larger, fully integrated system now under development, based upon a microelectrode array (MEA) with on-chip CMOS circuitry for recording and stimulation of electrogenic cells (e.g. neurons, cardiomyocytes). As a critical system unit, the microfluidics must be carefully designed and characterized to ensure that candidate drugs are delivered to specific regions of the culture at known concentrations. Furthermore, microfluidic design and functionality is dictated by the size, geometry, and material/electrical characteristics of the CMOS MEA. Therefore, this paper reports on the design considerations and fabrication of the flow cell, including theoretical and experimental analysis of the mass transfer properties of the nutrient and drug flows, which are in good agreement with one another. To demonstrate proof of concept, the flow cell was mounted on a dummy CMOS chip, which had been plated with HL-1 cardiomyocytes. A test chemical compound was delivered to the cell culture in a spatially resolved manner. Envisioned applications of this stand-alone system include simultaneous toxicological testing of multiple compounds and chemical stimulation of natural neural networks for neuroscience investigations.

Algorithms↗

Microfluidics/CMOS orthogonal capabilities for cell biology.

The study of individual cells and cellular networks can greatly benefit from the capabilities of microfabricated devices for the stimulation and the recording of electrical cellular events. In this contribution, we describe the development of a device, which combines capabilities for both electrical and pharmacological cell stimulation, and the subsequent recording of electrical cellular activity. The device combines the unique advantages of integrated circuitry (CMOS technology) for signal processing and microfluidics for drug delivery. Both techniques are ideally suited to study electrogenic mammalian cells, because feature sizes are of the same order as the cell diameter, approximately 50 microm. Despite these attractive features, we observe a size mismatch between microfluidic devices, with bulky fluidic connections to the outside world, and highly miniaturized CMOS chips. To overcome this problem, we developed a microfluidic flow cell that accommodates a small CMOS chip. We simulated the performances of a flow cell based on a 3-D microfluidic system, and then fabricated the device to experimentally verify the nutrient delivery and localized drug delivery performance. The flow-cell has a constant nutrient flow, and six drug inlets that can individually deliver a drug to the cells. The experimental analysis of the nutrient and drug flow mass transfer properties in the flowcell are in good agreement with our simulations. For an experimental proof-of-principle, we successfully delivered, in a spatially resolved manner, a 'drug' to a culture of HL-1 cardiac myocytes.

Cell Culture Techniques↗

Drops and falls.

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Accidental Falls↗

Ocular hypotensive efficacy and safety of brinzolamide ophthalmic suspension 1% added to travoprost ophthalmic solution 0.004% therapy in patients with open-angle glaucoma or ocular hypertension.

OBJECTIVE: The primary objective of this study was to determine if combined travoprost ophthalmic solution 0.004% and brinzolamide ophthalmic suspension 1% therapy is superior in lowering intraocular pressure (IOP) compared to travoprost monotherapy for patients with open angle glaucoma or ocular hypertension. The secondary objective was to measure the percentage of patients achieving IOP levels of 18 mmHg or less. STUDY DESIGN AND METHODS: Single arm, open-label. PARTICIPANTS: eighty-two patients with inadequate IOP control with travoprost monotherapy. INTERVENTION: the addition of brinzolamide ophthalmic suspension 1% twice daily. MAIN OUTCOME MEASURES: The primary endpoint was mean IOP reduction from baseline at 4 and 12 weeks. The percentage of patients who achieved IOP values <or= 18 mmHg was also measured. RESULTS: The mean age of the patients was 67 years. Ethnic origin was 92.7% Caucasian, 3.7% Black, 2.4% Asian and 1.2% other. The mean duration of travoprost treatment before the trial started was 30 weeks. Compared to the baseline data (IOP = 22.5 mmHg) with travoprost ophthalmic solution 0.004% monotherapy, IOP was decreased after 4 (n = 78) and 12 (n = 71) weeks of combined travoprost and brinzolamide therapy by an average of 3.9 mmHg (17.4%) and 4.2 mmHg (18.4%), respectively. At baseline 6.3% of patients had an IOP of 18 mmHg or less whereas at 4 and 12 weeks, 53.8% and 60.6% of patients respectively had an IOP of 18 mmHg or less. Common adverse events were mild and included ocular hyperaemia, dysgeusia and eye irritation. STUDY LIMITATIONS: this study had a small sample size and was open-label. CONCLUSION: Patients receiving combined travoprost ophthalmic solution 0.004% and brinzolamide ophthalmic suspension 1% therapy had lower IOP values compared to those on travoprost monotherapy (p < 0.0001). Combined therapy resulted in a significantly greater percentage of patients achieving IOPs of 18 mmHg or less (p < 0.0001).

Adult↗

Impedance characterization and modeling of electrodes for biomedical applications.

A low electrode-electrolyte impedance interface is critical in the design of electrodes for biomedical applications. To design low-impedance interfaces a complete understanding of the physical processes contributing to the impedance is required. In this work a model describing these physical processes is validated and extended to quantify the effect of organic coatings and incubation time. Electrochemical impedance spectroscopy has been used to electrically characterize the interface for various electrode materials: platinum, platinum black, and titanium nitride; and varying electrode sizes: 1 cm2, and 900 microm2. An equivalent circuit model comprising an interface capacitance, shunted by a charge transfer resistance, in series with the solution resistance has been fitted to the experimental results. Theoretical equations have been used to calculate the interface capacitance impedance and the solution resistance, yielding results that correspond well with the fitted parameter values, thereby confirming the validity of the equations. The effect of incubation time, and two organic cell-adhesion promoting coatings, poly-L-lysine and laminin, on the interface impedance has been quantified using the model. This demonstrates the benefits of using this model in developing better understanding of the physical processes occurring at the interface in more complex, biomedically relevant situations.

Biomedical Engineering↗

Results of the betaxolol versus placebo treatment trial in ocular hypertension.

PURPOSE: To determine whether treatment with betaxolol can delay or prevent the conversion from ocular hypertension to early glaucoma on the basis of visual field criteria, by means of a prospective, randomised, placebo-controlled trial. METHODS: Three hundred and fifty-six ocular hypertensives were randomized to treatment with either betaxolol drops or placebo drops during the period 1992-1996. Each patient was followed prospectively with 4-monthly visits. Examination at each visit included visual field testing, intra-ocular pressure (IOP) measurement and optic disc imaging. Conversion to early glaucoma was defined on the basis of visual field change by AGIS criteria. An intent-to-treat analysis compared visual field conversion after 3 years in the treatment and placebo arms. Normal visual field survival analysis was also performed. The IOP characteristics of the two treatment groups were compared. RESULTS: Two hundred and fifty-five patients completed the study, which ended in 1998, with a range of follow-up of 2-6 years. Sixteen (13.2%) of 121 patients in the placebo group converted to glaucoma, compared with 12 (9.0%) of 134 patients in the betaxolol group. The intent-to-treat analysis demonstrated no evidence of any difference in conversion rates between the betaxolol and placebo groups after 3 years. Visual field survival analysis demonstrated no significant difference between the betaxolol and placebo groups. The betaxolol-treated group had significantly lower post-treatment IOP values. Converters had significantly higher pre- and post-treatment IOP values than non-converters. CONCLUSIONS: Betaxolol significantly lowered the IOP level compared with placebo. Conversion to glaucoma was found to be related to both the baseline and post-treatment IOP levels. However the intent-to-treat analysis did not demonstrate a statistically significant reduction in the conversion rate in the betaxolol-treated group.

Adrenergic beta-Antagonists↗

Supraorbital nerve block in trabeculectomy surgery: an observational case series.

Thirteen patients completed a visual analogue pain scale after trabeculectomy with topical anaesthesia and a supraorbital nerve block with 2 mL of lignocaine 2%. Ease of surgery was graded on a scale of 0-5. Inadvertent eye movements and episodes of orbicularis spasm were recorded. Statistical analysis was performed using STATA software. Median pain score (range) during delivery of anaesthesia was 2 (1-5), during surgery was 0 (0-4) and postoperatively was 0 (0-3). Pain scores after surgery were significantly lower than during delivery of anaesthesia (Wilcoxon signed rank test, P = 0.0289). Three subjects had inadvertent eye movements with ease of surgery recorded as 1 of 5 in 12 cases and 2 of 5 in one case. The novel application of this anaesthetic technique offers adequate analgesia in trabeculectomy surgery. However, a larger scale comparative trial is needed to further evaluate the value of this technique.

Aged↗