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3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate.

Gowers SA, Curto VF, Seneci CA, Wang C, Anastasova S, Vadgama P, Yang GZ, Boutelle MG - Anal. Chem. (2015)

Bottom Line: A soft compressible 3D printed elastomer at the base of the holder ensures a good seal with the microfluidic chip.Optimization of the channel size significantly improves the response time of the sensor.As a proof-of-concept study, our microfluidic device was coupled to lab-built wireless potentiostats and used to monitor real-time subcutaneous glucose and lactate levels in cyclists undergoing a training regime.

View Article: PubMed Central - PubMed

Affiliation: §School of Engineering and Materials Science, Queen Mary, University of London, Mile End Road, London E1 4NS, United Kingdom.

ABSTRACT
This work presents the design, fabrication, and characterization of a robust 3D printed microfluidic analysis system that integrates with FDA-approved clinical microdialysis probes for continuous monitoring of human tissue metabolite levels. The microfluidic device incorporates removable needle type integrated biosensors for glucose and lactate, which are optimized for high tissue concentrations, housed in novel 3D printed electrode holders. A soft compressible 3D printed elastomer at the base of the holder ensures a good seal with the microfluidic chip. Optimization of the channel size significantly improves the response time of the sensor. As a proof-of-concept study, our microfluidic device was coupled to lab-built wireless potentiostats and used to monitor real-time subcutaneous glucose and lactate levels in cyclists undergoing a training regime.

No MeSH data available.


A. Photographof microfluidic device to measure tissue glucoseand lactate levels in dialysate during the cycling protocol. Dialysateflowed into the microfluidic chip, housing the glucose and lactatebiosensors, which were connected to wireless potentiostats, securedonto the bike. B. Experimental protocol. Tissue levels were monitoredduring an initial resting period (i), followed bycycling at 4 levels of increasing rpm (ii-v), a levelof warming down (vi), and a final period of resting(vii). C. Dialysate glucose and lactate levels duringthe exercise phase of the cycling protocol. The bottom graph showsthe glucose (red) and lactate (green) levels, the middle graph (black)shows the lactate/glucose ratio, and the top graph shows the rotationsper minute (blue) and heart rate (purple) throughout the cycling protocol.Glucose and lactate traces have been despiked.39 The dotted lines indicate the stages of varying cyclingintensity: (ii) 55 rpm, (iii) 65rpm, (iv) 75 rpm, (v) sprint, and(vi) 55 rpm. Data has been time-aligned, taking intoaccount the time delay of the system. D. Histograms showing mean dialysatelevels for two different cyclists during key points in cycling protocol.Labels correspond to stages described in the experimental protocol:(i) baseline (ii) midway throughwarm up, (iii) midway through medium intensity, (iv) midway through high intensity, (v) end of sprint, (vi) end of warm down, and (vii) after 50min of recovery.
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fig4: A. Photographof microfluidic device to measure tissue glucoseand lactate levels in dialysate during the cycling protocol. Dialysateflowed into the microfluidic chip, housing the glucose and lactatebiosensors, which were connected to wireless potentiostats, securedonto the bike. B. Experimental protocol. Tissue levels were monitoredduring an initial resting period (i), followed bycycling at 4 levels of increasing rpm (ii-v), a levelof warming down (vi), and a final period of resting(vii). C. Dialysate glucose and lactate levels duringthe exercise phase of the cycling protocol. The bottom graph showsthe glucose (red) and lactate (green) levels, the middle graph (black)shows the lactate/glucose ratio, and the top graph shows the rotationsper minute (blue) and heart rate (purple) throughout the cycling protocol.Glucose and lactate traces have been despiked.39 The dotted lines indicate the stages of varying cyclingintensity: (ii) 55 rpm, (iii) 65rpm, (iv) 75 rpm, (v) sprint, and(vi) 55 rpm. Data has been time-aligned, taking intoaccount the time delay of the system. D. Histograms showing mean dialysatelevels for two different cyclists during key points in cycling protocol.Labels correspond to stages described in the experimental protocol:(i) baseline (ii) midway throughwarm up, (iii) midway through medium intensity, (iv) midway through high intensity, (v) end of sprint, (vi) end of warm down, and (vii) after 50min of recovery.

Mentions: For invivo microdialysisexperiments, all procedures were approved by the local ethics committee(NRES 10/H0808/124, protocol CRO1608), and probes were inserted percutaneouslyby a qualified clinician. The skin was cleaned with alcohol wipes,and an anesthetic cream (EMLA, APP Pharmaceuticals) was applied tothe skin 45 min prior to probe insertion. An ice pack was also placedon the skin 5 min before probe insertion, to further numb the area.A sterile CMA63 microdialysis probe (Mdialysis, 10 mm membrane length,20 kDa molecular-weight cutoff) was inserted subcutaneously, usingthe tunnelling needle and introducer supplied, and secured in placewith 3M single coated conformable incise medical tape. The probe wasperfused with sterile T1 perfusion solution (MDialysis) at 1 μL/minusing a microdialysis pump (CMA107, MDialysis). Prior to beginningexercise, baseline dialysate levels of glucose and lactate were measured.The cycling protocol consisted of 3 levels of increasing intensity,followed by a 1 min sprint, and finally a warm-down phase, as shownin Figure 4-A. Dialysate glucose and lactatelevels were also recorded during the recovery phase immediately afterexercise.


3D Printed Microfluidic Device with Integrated Biosensors for Online Analysis of Subcutaneous Human Microdialysate.

Gowers SA, Curto VF, Seneci CA, Wang C, Anastasova S, Vadgama P, Yang GZ, Boutelle MG - Anal. Chem. (2015)

A. Photographof microfluidic device to measure tissue glucoseand lactate levels in dialysate during the cycling protocol. Dialysateflowed into the microfluidic chip, housing the glucose and lactatebiosensors, which were connected to wireless potentiostats, securedonto the bike. B. Experimental protocol. Tissue levels were monitoredduring an initial resting period (i), followed bycycling at 4 levels of increasing rpm (ii-v), a levelof warming down (vi), and a final period of resting(vii). C. Dialysate glucose and lactate levels duringthe exercise phase of the cycling protocol. The bottom graph showsthe glucose (red) and lactate (green) levels, the middle graph (black)shows the lactate/glucose ratio, and the top graph shows the rotationsper minute (blue) and heart rate (purple) throughout the cycling protocol.Glucose and lactate traces have been despiked.39 The dotted lines indicate the stages of varying cyclingintensity: (ii) 55 rpm, (iii) 65rpm, (iv) 75 rpm, (v) sprint, and(vi) 55 rpm. Data has been time-aligned, taking intoaccount the time delay of the system. D. Histograms showing mean dialysatelevels for two different cyclists during key points in cycling protocol.Labels correspond to stages described in the experimental protocol:(i) baseline (ii) midway throughwarm up, (iii) midway through medium intensity, (iv) midway through high intensity, (v) end of sprint, (vi) end of warm down, and (vii) after 50min of recovery.
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Related In: Results  -  Collection

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fig4: A. Photographof microfluidic device to measure tissue glucoseand lactate levels in dialysate during the cycling protocol. Dialysateflowed into the microfluidic chip, housing the glucose and lactatebiosensors, which were connected to wireless potentiostats, securedonto the bike. B. Experimental protocol. Tissue levels were monitoredduring an initial resting period (i), followed bycycling at 4 levels of increasing rpm (ii-v), a levelof warming down (vi), and a final period of resting(vii). C. Dialysate glucose and lactate levels duringthe exercise phase of the cycling protocol. The bottom graph showsthe glucose (red) and lactate (green) levels, the middle graph (black)shows the lactate/glucose ratio, and the top graph shows the rotationsper minute (blue) and heart rate (purple) throughout the cycling protocol.Glucose and lactate traces have been despiked.39 The dotted lines indicate the stages of varying cyclingintensity: (ii) 55 rpm, (iii) 65rpm, (iv) 75 rpm, (v) sprint, and(vi) 55 rpm. Data has been time-aligned, taking intoaccount the time delay of the system. D. Histograms showing mean dialysatelevels for two different cyclists during key points in cycling protocol.Labels correspond to stages described in the experimental protocol:(i) baseline (ii) midway throughwarm up, (iii) midway through medium intensity, (iv) midway through high intensity, (v) end of sprint, (vi) end of warm down, and (vii) after 50min of recovery.
Mentions: For invivo microdialysisexperiments, all procedures were approved by the local ethics committee(NRES 10/H0808/124, protocol CRO1608), and probes were inserted percutaneouslyby a qualified clinician. The skin was cleaned with alcohol wipes,and an anesthetic cream (EMLA, APP Pharmaceuticals) was applied tothe skin 45 min prior to probe insertion. An ice pack was also placedon the skin 5 min before probe insertion, to further numb the area.A sterile CMA63 microdialysis probe (Mdialysis, 10 mm membrane length,20 kDa molecular-weight cutoff) was inserted subcutaneously, usingthe tunnelling needle and introducer supplied, and secured in placewith 3M single coated conformable incise medical tape. The probe wasperfused with sterile T1 perfusion solution (MDialysis) at 1 μL/minusing a microdialysis pump (CMA107, MDialysis). Prior to beginningexercise, baseline dialysate levels of glucose and lactate were measured.The cycling protocol consisted of 3 levels of increasing intensity,followed by a 1 min sprint, and finally a warm-down phase, as shownin Figure 4-A. Dialysate glucose and lactatelevels were also recorded during the recovery phase immediately afterexercise.

Bottom Line: A soft compressible 3D printed elastomer at the base of the holder ensures a good seal with the microfluidic chip.Optimization of the channel size significantly improves the response time of the sensor.As a proof-of-concept study, our microfluidic device was coupled to lab-built wireless potentiostats and used to monitor real-time subcutaneous glucose and lactate levels in cyclists undergoing a training regime.

View Article: PubMed Central - PubMed

Affiliation: §School of Engineering and Materials Science, Queen Mary, University of London, Mile End Road, London E1 4NS, United Kingdom.

ABSTRACT
This work presents the design, fabrication, and characterization of a robust 3D printed microfluidic analysis system that integrates with FDA-approved clinical microdialysis probes for continuous monitoring of human tissue metabolite levels. The microfluidic device incorporates removable needle type integrated biosensors for glucose and lactate, which are optimized for high tissue concentrations, housed in novel 3D printed electrode holders. A soft compressible 3D printed elastomer at the base of the holder ensures a good seal with the microfluidic chip. Optimization of the channel size significantly improves the response time of the sensor. As a proof-of-concept study, our microfluidic device was coupled to lab-built wireless potentiostats and used to monitor real-time subcutaneous glucose and lactate levels in cyclists undergoing a training regime.

No MeSH data available.