Discrete Chemical Release From a microfluidic Chip

Hu, Min; Lindemann, T.; Göttsche, Thorsten; Kohnle, J.; Zengerle, Roland; Koltay, Peter

doi:10.1109/memsys.2006.1627728

Cited by 7 publications

(10 citation statements)

References 7 publications

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“…Earlier attempts to use microfluidic devices for chemical stimulation of cells suffered from the problem of uncontrolled leakage from open microapertures into the medium and consequently undefined concentration conditions (4,5). In contrast, our novel ''air gap''-scheme (6) (Fig. 1) avoids such leakage completely.…”

Section: Introductionmentioning

confidence: 85%

Localized Functional Chemical Stimulation of TE 671 Cells Cultured on Nanoporous Membrane by Calcein and Acetylcholine

Zibek

Stett

Koltay³

et al. 2007

Biophysical Journal

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Acetylcholine sensitive TE 671 cells were cultured on nanoporous membranes and chemically stimulated by localized application of i), calcein-AM and ii), acetylcholine, respectively, onto the bottom face of the membrane employing an ink jet print head. Stimulus correlated response of cells was recorded by fluorescence microscopy with temporal and spatial resolution. Calcein fluorescence develops as a result of intracellular enzymatic conversion of calcein-AM, whereas Ca(2+) imaging using fluo-4 dye was employed to visualize cellular response to acetylcholine stimulation. Using 25 pl droplets and substance concentration ranging from 10 microM to 1 mM on Nucleopore membranes with pore diameters between 50 nm and 1 microm, a resolution on the order of 50 microm was achieved.

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Section: Introductionmentioning

confidence: 85%

Localized Functional Chemical Stimulation of TE 671 Cells Cultured on Nanoporous Membrane by Calcein and Acetylcholine

Zibek

Stett

Koltay³

et al. 2007

Biophysical Journal

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“…For another potential use of this device, treating angina, the IRD3 could be implanted in high‐risk patients to deliver vasodilators such as nitrates on demand. Hu et al28 provide an example of a similar implementation of pulsed liquid ejection to accurately achieve sub‐nL volume bursts from a microchip reservoir.…”

Section: Rationale For Mems‐based Implantable Medical Devicesmentioning

confidence: 99%

“…There is a fundamental limitation of device size imposed by the need to have sufficient storage capacity for a chronic dosing regimen, and even the most potent drugs require microgram quantities per day. Peptide formulation development has demonstrated that highly concentrated (>100 mg/mL) peptide solutions (leuprolide and human parathyroid hormone [hPTH] (1–34)) can be prepared, filled in microchip reservoirs, and lyophilized 68,69…”

Section: Implantable Mems‐based Drug Delivery Systems: Design and Commentioning

confidence: 99%

“…The same system was tested to deliver the 34‐amino acid N‐terminal fragment of hPTH. (1–34) Intermittent bursts of PTH are required to induce bone growth 102–105. A lyophilized formulation was developed that was successfully released (as shown in Figure 9) with the necessary reproducible pulsatile release 98.…”

Section: Implantable Mems‐based Drug Delivery Systems: Control Of Relmentioning

confidence: 99%

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Microchips and controlled‐release drug reservoirs

Staples¹

2010

WIREs Nanomed Nanobiotechnol

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This review summarizes and updates the development of implantable microchip-containing devices that control dosing from drug reservoirs integrated with the devices. As the expense and risk of new drug development continues to increase, technologies that make the best use of existing therapeutics may add significant value. Trends of future medical care that may require advanced drug delivery systems include individualized therapy and the capability to automate drug delivery. Implantable drug delivery devices that promise to address these anticipated needs have been constructed in a variety of ways using micro- and nanoelectromechanical systems (MEMS or NEMS)-based technology. These devices expand treatment options for addressing unmet medical needs related to dosing. Within the last few years, advances in several technologies (MEMS or NEMS fabrication, materials science, polymer chemistry, and data management) have converged to enable the construction of miniaturized implantable devices for controlled delivery of therapeutic agents from one or more reservoirs. Suboptimal performance of conventional dosing methods in terms of safety, efficacy, pain, or convenience can be improved with advanced delivery devices. Microchip-based implantable drug delivery devices allow localized delivery by direct placement of the device at the treatment site, delivery on demand (emergency administration, pulsatile, or adjustable continuous dosing), programmable dosing cycles, automated delivery of multiple drugs, and dosing in response to physiological and diagnostic feedback. In addition, innovative drug-medical device combinations may protect labile active ingredients within hermetically sealed reservoirs.

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“…These devices, however, usually have complicated structure and fabrication, only allow relatively small delivery rates, require long response times to control signals, and also have problems in unintended drug release due to diffusion. The use of discrete droplets would minimize diffusive drug leakage while allowing delivery of minute drug volumes [20], but their inability to deliver drugs at specified locations in tissue is undesirable for neurobiological studies. Moreover, microfluidic devices integrating microflow regulation components [21] and drug delivery routes [22] are used for local delivery of drugs with the dosage varied in situ .…”

Section: Introductionmentioning

confidence: 99%

A Microfluidic Approach to Pulsatile Delivery of Drugs for Neurobiological Studies

Wang

Litvin

et al. 2012

J. Microelectromech. Syst.

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We present an innovative microfluidic approach to transcranial delivery of small quantities of drugs in brief time pulses for neurobiological studies. The approach is based on a two-stage process of consecutive drug dispensing and delivery, demonstrated by a device featuring a fully planar design in which the microfluidic components are integrated in a single layer. This 2-D configuration offers ease in device fabrication and is compatible to diverse actuation schemes. A compliance-based and normally closed check valve is used to couple the microchannels that are responsible for drug dispensing and delivery. Brief pneumatic pressure pulses are used to mobilize buffer and drug solutions, which are injected via a cannula into brain tissue. Thus, the device can potentially allow transcranial drug delivery and can also be potentially extended to enable transdermal drug delivery. We have characterized the device by measuring the dispensed and delivered volumes under varying pneumatic driving pressures and pulse durations, the standby diffusive leakage, and the repeatability in the delivery of multiple pulses of drug solutions. Results demonstrate that the device is capable of accurately dispensing and delivering drug solutions 5 to 70 nL in volume within time pulses as brief as 50 ms, with negligible diffusive drug leakage over a practically relevant time scale. Furthermore, testing of pulsatile drug delivery into intact mouse brain tissue has been performed to demonstrate the potential application of the device to neurobiology.

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Discrete Chemical Release From a microfluidic Chip

Cited by 7 publications

References 7 publications

Localized Functional Chemical Stimulation of TE 671 Cells Cultured on Nanoporous Membrane by Calcein and Acetylcholine

Localized Functional Chemical Stimulation of TE 671 Cells Cultured on Nanoporous Membrane by Calcein and Acetylcholine

Microchips and controlled‐release drug reservoirs

A Microfluidic Approach to Pulsatile Delivery of Drugs for Neurobiological Studies

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