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Bioelectronic measurement and feedback control of molecules in living cells

Published in:
Sci. Rep., Vol. 7, No. 1, 2 October 2017, 12511.

Summary

We describe an electrochemical measurement technique that enables bioelectronic measurements of reporter proteins in living cells as an alternative to traditional optical fluorescence. Using electronically programmable microfluidics, the measurement is in turn used to control the concentration of an inducer input that regulates production of the protein from a genetic promoter. The resulting bioelectronic and microfluidic negative-feedback loop then serves to regulate the concentration of the protein in the cell. We show measurements wherein a user-programmable set-point precisely alters the protein concentration in the cell with feedback-loop parameters affecting the dynamics of the closed-loop response in a predictable fashion. Our work does not require expensive optical fluorescence measurement techniques that are prone to toxicity in chronic settings, sophisticated time-lapse microscopy, or bulky/expensive chemo-stat instrumentation for dynamic measurement and control of biomolecules in cells. Therefore, it may be useful in creating a: cheap, portable, chronic, dynamic, and precise all-electronic alternative for measurement and control of molecules in living cells.
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Summary

We describe an electrochemical measurement technique that enables bioelectronic measurements of reporter proteins in living cells as an alternative to traditional optical fluorescence. Using electronically programmable microfluidics, the measurement is in turn used to control the concentration of an inducer input that regulates production of the protein from a genetic...

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Flexible glucose sensors and fuel cells for bioelectronic implants

Published in:
IEEE 60th Int. Midwest Symp. on Circuits and Systems, MWSCAS, 6-9 August 2017.

Summary

Microfabrication techniques were developed to create flexible 24 um thick glucose sensors on polyimide substrates. Measurements of the sensor performance, recorded as voltage potential, were carried out for a range of glucose concentrations (0 – 8 mM) in physiological saline (0.1 M NaCl, pH 7.4). The sensors show rapid response times (seconds to stable potential) and good sensitivity in the 0 – 4 mM range. Additionally, we demonstrate that the sensors can operate as fuel cells, generating peak power levels up to 0.94 uW/cm2. Such flexible devices, which can be rolled up to increase surface area within a fixed volume, may enable ultra-low-power bio-electronic implants for glucose sensing or glucose energy harvesting in the future.
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Summary

Microfabrication techniques were developed to create flexible 24 um thick glucose sensors on polyimide substrates. Measurements of the sensor performance, recorded as voltage potential, were carried out for a range of glucose concentrations (0 – 8 mM) in physiological saline (0.1 M NaCl, pH 7.4). The sensors show rapid response...

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Fluidic microoptics with adjustable focusing and beam steering for single cell optogenetics

Published in:
Opt. Express, Vol. 25, No. 14, 10 July 2017, pp. 16825-16839.

Summary

Electrically controlled micron-scale liquid lenses have been designed, fabricated and demonstrated, that provide both adjustable focusing and beam steering, with the goal of applying them to optogenetic in vivo mapping of brain activity with single cell resolution. The liquid lens is formed by the interface between two immiscible liquids which are contained in a conically tapered lens cavity etched into a fused silica substrate. Interdigitated electrodes have been patterned along the sidewall of the taper to control the liquid lens curvature and tilt. Microlenses with apertures ranging in size from 30 to 80 μm were fabricated and tunable focusing ranging from 0.25 to 3 mm and beam steering of ± 1 degree have been demonstrated.
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Summary

Electrically controlled micron-scale liquid lenses have been designed, fabricated and demonstrated, that provide both adjustable focusing and beam steering, with the goal of applying them to optogenetic in vivo mapping of brain activity with single cell resolution. The liquid lens is formed by the interface between two immiscible liquids which...

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Open-source, community-driven microfluidics with Metafluidics

Summary

Microfluidic devices have the potential to automate and miniaturize biological experiments, but open-source sharing of device designs has lagged behind sharing of other resources such as software. Synthetic biologists have used microfluidics for DNA assembly, cell-free expression, and cell culture, but a combination of expense, device complexity, and reliance on custom set-ups hampers their widespread adoption. We present Metafluidics, an open-source, community-driven repository that hosts digital design files, assembly specifications, and open-source software to enable users to build, configure, and operate a microfluidic device. We use Metafluidics to share designs and fabrication instructions for both a microfluidic ring-mixer device and a 32-channel tabletop microfluidic controller. This device and controller are applied to build genetic circuits using standard DNA assembly methods including ligation, Gateway, Gibson, and Golden Gate. Metafluidics is intended to enable a broad community of engineers, DIY enthusiasts, and other nontraditional participants with limited fabrication skills to contribute to microfluidic research.
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Summary

Microfluidic devices have the potential to automate and miniaturize biological experiments, but open-source sharing of device designs has lagged behind sharing of other resources such as software. Synthetic biologists have used microfluidics for DNA assembly, cell-free expression, and cell culture, but a combination of expense, device complexity, and reliance on...

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Microhydraulic electrowetting actuators

Published in:
J. Microelectromech. Syst., Vol. 25, No. 2, April 2016, pp. 394-400.

Summary

The conversion of electrical to mechanical power on a sub-centimeter scale is a key technology in many microsystems and energy harvesting devices. In this paper, we present a type of a capacitive energy conversion device that uses capillary pressure and electrowetting to reversibly convert electrical power to hydraulic power. These microhydraulic actuators use a high surface-to-volume ratio to deliver high power at a relatively low voltage with an energy conversion efficiency of over 65%. The capillary pressure generated grows linearly with shrinking capillary diameter, as does the frequency of actuation. We present the pressure, frequency, and power scaling properties of these actuators and demonstrate that power density scales up as the inverse capillary diameter squared, leading to high-efficiency actuators with a strength density exceeding biological muscle. Two potential applications for microhydraulics are also demonstrated: soft-microrobotics and energy harvesting.
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Summary

The conversion of electrical to mechanical power on a sub-centimeter scale is a key technology in many microsystems and energy harvesting devices. In this paper, we present a type of a capacitive energy conversion device that uses capillary pressure and electrowetting to reversibly convert electrical power to hydraulic power. These...

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In situ microfluidic SERS assay for monitoring enzymatic breakdown of organophosphates

Summary

In this paper, we report on a method to probe the breakdown of the organophosphate (OP) simulants o, s-diethyl methyl phosphonothioate (OSDMP) and demeton S by the enzyme organophosphorous hydrolase (OPH) in a microfluidic device by surface enhanced Raman spectroscopy (SERS). SERS hotspots were formed on-demand inside the microfluidic device by laser-induced aggregation of injected Ag NPs suspensions. The Ag NP clusters, covering micron-sized areas, were formed within minutes using a conventional confocal Raman laser microscope. These Ag NP clusters were used to enhance the Raman spectra of the thiol products of OP breakdown in the microfluidic device: ethanethiol (EtSH) and (ethylsulfanyl) ethane-1-thiol (2-EET). When the OPH enzyme and its substrates OSDMP and demeton S were introduced, the thiolated breakdown products were generated, resulting in changes in the SERS spectra. With the ability to analyze reaction volumes as low as 20 nL, our approach demonstrates great potential for miniaturization of SERS analytical protocols.
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Summary

In this paper, we report on a method to probe the breakdown of the organophosphate (OP) simulants o, s-diethyl methyl phosphonothioate (OSDMP) and demeton S by the enzyme organophosphorous hydrolase (OPH) in a microfluidic device by surface enhanced Raman spectroscopy (SERS). SERS hotspots were formed on-demand inside the microfluidic device...

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Development of adaptive liquid microlenses and microlens arrays

Published in:
SPIE Photonics West 2013: MOEMS-MEMS, 2-7 February 2013.

Summary

We report on the development of sub-millimeter size adaptive liquid microlenses and microlens arrays using two immiscible liquids to form individual lenses. Microlenses and microlens arrays having aperture diameters as small as 50 microns were fabricated on a planar quartz substrate using patterned hydrophobic/hydrophilic regions. Liquid lenses were formed by a self-assembled oil dosing process that created well-defined lenses having a high fill factor. Variable focus was achieved by controlling the lens curvature through electrowetting. Greater than 70 degrees of contact angle change was achieved with less than 20 volts, which results in a large optical power dynamic range.
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Summary

We report on the development of sub-millimeter size adaptive liquid microlenses and microlens arrays using two immiscible liquids to form individual lenses. Microlenses and microlens arrays having aperture diameters as small as 50 microns were fabricated on a planar quartz substrate using patterned hydrophobic/hydrophilic regions. Liquid lenses were formed by...

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