For example, the density of metabolites in sweat — along with its ease of collection from skin pores — make it a useful biofluidic candidate for analysis. One recent study looked at how microchannels and micro reservoirs, pre-filled with fluorescent probes that react to target analytes in sweat, can perform quantitative analysis. To capture sweat, fluorometric sensing modalities were integrated into a skin-interfaced microfluidic system that was paired with a smartphone-based imaging module. This method yielded an accurate measurement of biomarkers in sweat.

In another recent study, researchers developed wearable sensors to monitor biomolecule levels by combining continuous fluid sampling with in-situ analysis. Depending upon the target biomolecule, the particular assay was interchangeable.

The microfluidic device featured a droplet-flow method for timing, and a micropump to produce nanolitre-sized droplets. Biomarker variations within fluids, over time, yield insight into tissue physiology and may help to create personalized treatments.

The study’s palm-sized sensor autonomously detected deviations from steady-state level.“We demonstrate how the sensor can track perturbed glucose and lactate levels in dermal tissue with results in close agreement with standard off-line analysis and consistent with changes in peripheral blood levels,” the authors wrote.

Biomarker concentrations fluctuate continuously, as does chemical signalling. The capacity for continuous measurement of these dynamics has significant implications.

Many current point-of-care devices are single-measurement tools. The use of microfluidics for continuous monitoring has been strained where microfluidic systems rely upon bulky laboratory equipment such as syringe pumps and microscopes — impractical as wearable devices. But recent advances address this.

For example, the linear nature of microscale flow has required many external control devices. Another recent study, by an international research team, highlights the design of networks with a nonlinear relation between flow rate and its applied pressure. This relation can be harnessed to switch the direction of internal flows by manipulating the input and output pressures.

Using rigid polymer channels to carry water, the investigators showed that these networks demonstrate a fluid version of Braess’s Paradox: closing an intermediate channel resulted in a higher rather than lower, total flow rate. These findings are scalable and can implement flow routing with multiple switches. Practical applications can encompass built-in control mechanisms in microfluidic networks, furthering the creation of portable systems — such as wearable healthcare technologies

These new findings seem to have clear advantages, yet final shepherding of new findings toward commercialization remains the most challenging step. A new device can fail clinically, or it can run out of funding, miscalculate the market, or collide with regulations, according to Georgia Tech benchtop-to-bedside expert Tiffany Wilson.

“Find out about clinical workflow and how health care operates, then maybe decide not to pursue the prototype you had planned, but work on a new one instead,” she warns. “It generally doesn’t work to take what was built in the lab and make the same thing with medical-grade materials, and unfortunately, many researchers don’t realize this until it’s too late.”

And, she notes, “Words matter. For example, if I want to market my new catheter as ‘pain-free,’ the FDA may want me to conduct an expensive clinical trial, but if I take that same catheter and market it as ‘low friction,’ which is why it’s pain-free, then I can demonstrate that with simple bench tests.”

The variety of viewpoints should not be underestimated. “Many stakeholders need their questions answered,” Wilson said. The clinician is only a part of the equation. The hospital supply chain may not be able to handle it. Regulators may not approve it.

“Also, know your competition,” Wilson advised. “Are you more competitive than the current standard of care?”

Yes, we are, microfluidics pioneers can now confirm.

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Kathy Jean Schultz

Kathy Jean Schultz is a freelance medical science writer who focuses on medical innovations. She earned a Master’s Degree in Research Methodology from Hofstra University, and a Master’s Degree in Psychology from Long Island University. She is a member of the National Association of Science Writers, and the Association of Health Care Journalists. Her articles about organoids include "Would you trust a 3-D printed mini organ to test your drugs?" and "Stem cells not only slow disease, they come with their own safety test".

• http://kathyjeanschultz.pressfolios.com/

The post Wearable Technology Innovations are Fueled by Microfluidics Research appeared first on The MicroFluidic Circle.

• Label-free continuous monitoring of cell health inside channels
• Low volumes (picoliters) in microfluidic channels enable high sensitivity of detection
• By placing sensors close to the cells, the analyte of interest is less likely to be diluted in cell media

Truly mimicking human physiology

Living cells are sensitive even to the slightest changes in their environment and release certain molecules in response to these changes. Monitoring these molecules provides valuable information on the state of health and can predict response to drugs. For example, Zhang et al.¹ developed a multi-sensor integrated organ-on-chip platform to monitor micro-environmental parameters such as pH, oxygen, and temperature by using optical-based sensors. Additionally, the authors developed label-free electrochemical immunobiosensors for continuous monitoring of molecules secreted by tissue-engineered organs inside the microfluidic channels. This work demonstrated that organ-on-chips can integrate real-time monitoring of the biophysical and biochemical parameters in a micro-environment.

Figure 1: Schematic showing how sensors can be used to continuously monitor biochemical parameters inside a microfluidic channel.
Credit: Aditya Aryasomayajula

Figure 1 shows a schematic diagram of how feedback from the sensors integrated into a microfluidic channel can be used for regulating the microenvironment for cell culture. Sensors can continuously monitor biophysical and biochemical parameters inside a channel and directly communicate this information to a computer, which in turn adjusts the inflow of fresh cell culture media using a pump. Thismicroperfusion of the channel with cell culture media can help maintain an optimal pH, oxygen level, and temperature. This feedback can be used to improve cell viability for organ-on-chip applications and bring us a step closer to truly mimicking the human physiology.

Currently, there are developed sensors for measurement of pH², oxygen³, glucose³ and lactate⁴. Integrating any combination of these sensors into organ-on-chip devices will help define the microenvironment that may be important in drug screening applications.

Challenges integrating sensors and outlook

There are several challenges that one has to overcome in order to successfully integrate sensors into microfluidic channels. They are as follows:

a. Biofouling
One of the major challenges of using sensors for long-term monitoring is biofouling of the surface. Biofouling refers to the forming of a thin biofilm on the surface of the sensing material which results in degrading the performance of the sensors. This problem is particularly amplified when sensing in biological environments. There have been several strategies to mitigate biofouling of sensors. For example, surface modification (silanization) is a popular technique to extend the life of sensors.

b. Fabrication technologies
The conventional use of soft lithography for fabricating microfluidic devices requires modifications to integrate sensors directly into the channels. Problems, such as bonding of PDMS surface and aligning sensors inside channels, may be a challenge. New fabrication techniques like LEGO and cartridge assemblies have gained popularity for manufacturing organ-on-chip devices, as these are better suited for sensor integration.

c. Sensor sensitivity and selectivity
Sensor sensitivity refers to the detection limit of the sensors. Ultrasensitive sensors are required for sensing in low volumes (picoliters) in the mg/L or ng/L range. Recently nanomaterials like graphene⁵ and carbon nanotubes⁶ have gained popularity because of their high sensitivity to detect in low volumes. Selectivity is another major challenge for these sensors. This parameter refers to the ability of the sensors to detect only specific molecule of interest with high signal to noise ratio. The presence of various interfering species in cell culture media can be a challenge to sense specifically the molecule of interest. Aptamer-based sensors offer good selectivity with high signal to noise ratio.

In conclusion, new technology brings new demands and challenges. Organ-on-chip and tissue engineering show great promise for personalized medicine, drug development, and studying disease models with more complex physiologically relevant systems. Integrating sensors into microfluidic channels can enhance the performance of these technologies by continuous monitoring of biophysical and biochemical parameters in micro-environments.

<sup>1. Zhang, Y.S., Aleman, J., Shin, S.R., Kilic, T., Kim, D., Shaegh, S.A.M., Massa, S., Riahi, R., Chae, S., Hu, N. and Avci, H., 2017. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proceedings of the National Academy of Sciences, p.201612906.

2. Welch, D. and Christen, J.B., 2014. Real-time feedback control of pH within microfluidics using integrated sensing and actuation. Lab on a Chip, 14(6), pp.1191-1197.

3. Rodrigues, N.P., Sakai, Y. and Fujii, T., 2008. Cell-based microfluidic biochip for the electrochemical real-time monitoring of glucose and oxygen. Sensors and Actuators B: Chemical, 132(2), pp.608-613.

4. Weltin, A., Slotwinski, K., Kieninger, J., Moser, I., Jobst, G., Wego, M., Ehret, R. and Urban, G.A., 2014. Cell culture monitoring for drug screening and cancer research: a transparent, microfluidic, multi-sensor microsystem. Lab on a Chip, 14(1), pp.138-146.

5. Shao, Y., Wang, J., Wu, H., Liu, J., Aksay, I.A. and Lin, Y., 2010. Graphene based electrochemical sensors and biosensors: a review. Electroanalysis, 22(10), pp.1027-1036.

6. Jacobs, C.B., Peairs, M.J. and Venton, B.J., 2010. Carbon nanotube based electrochemical sensors for biomolecules. Analytica chimica acta, 662(2), pp.105-127.</sup>

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Aditya Aryasomayajula

Aditya currently holds a joint postdoctoral fellowship in Mechanical Engineering Department at McMaster University and Firestone Institute for Respiratory Health at St. Joseph’s Healthcare, Hamilton. He is also the project manager for the sensor division of Global Water Futures program. He has won prestigious scholarships from National Science Foundation (NSF) and Deutsche Forschungsgemeinschaft (DFG) Germany. His research interests include developing sensors for environmental monitoring and healthcare diagnostics. He is currently developing a lung-on-chip device to study disease models like asthma and drug screening for cystic fibrosis.

• aryasoma@mcmaster.ca

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