Phenylboronic based Glucose sensitive Hydrogel

Sugar sensitive Phenylboronic acid-based hydrogels: Towards glucose

analysis in sweatby

HENOK TESFAY

4th year project

Supervisors: Dr. Aoife Morrin,

Dr Larisa Elena Florea Dr. Colm Delaney

School of Chemical Sciences May 2016

1

Aim of the project

• To build implantable glucose sensors that can potentially detect glucose level in our body within a few minute.

2

Source: http://www. idf.org/about-diabetes 3

Diabetes is becoming a big problem in our society, affecting currently one in every 20 people in the world.

Prevalence of Diabetes • Diabetes caused

5.1 million deaths in 2013. Every six seconds a person dies from diabetes.

Source: http://www. idf.org/about-diabetes

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Is there a cure for Diabetes?• No cure for diabetes • Controlling blood glucose levels in

diabetic patients is really important but it is not easy.

• Nowadays, glucose monitoring is performed using devices that measure glucose in blood drops. 

• That implicates that all people with diabetes must prick their finger and test drops of blood throughout the day.

Source: http://www.slideshare.net/funk97 / glucose-monitoring-smart-watch

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• While blood test is the most known way of measuring glucose level, other available body fluids are becoming interesting targets for non-invasive glucose measurements. Such as : sweat, saliva and tears .

Source: google contact lens

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Complex between phenylboronic acid (PBA) moiety and a sugar molecule in aqueous solution

PBA bearing hydrogel

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Sugar

Photochemical polymerization(Gel forming reagents)

Acrylamide(AAm)

3-(Acrylamido) phenylboronic acid – (PBA)

sugar reactive monomer

2-Hydroxy-2-methpropiophene-(HMPP)

photo initiator

Methylenebisacrylamide (BIS)

Cross-linker

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20mol%PBA gel in Glucose

• Control

• In 4mM

• In 6mM

• In 10mM

• In 20 mM

20mol%PBA gel in Fructose

• Control

• In 4mM

• In 6mM

• In 10mM

• In 20mM

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20mol%PBA gel in Glucose 20mol%PBA gel in Fructose

Width (µm) Length(µm) Width(µm) Length(µm)

Control 3495.11 1185.65 3495.11 1185.65

4mM 4083.23 1381.65 5321.40 2123.96

6mM 4412.98 19333.18 5547.18 2123.86

10mM 4495.17 1690.87 5680.85 2309.53

20mM 4752.92 2216.65 5763.33 2825.02

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Time dependent swelling of Hydrogel in 10mM Fructose solution (5mol% PBA)

0 10 20 30 40 50 600

0.050.1

0.150.2

0.250.3

0.350.4

0.45

Fructose

Time in hrs

Swel

ling

Ratio

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Behaviour of 5mol% PBA Hydrogel in Glucose, Sucrose & Fructose Solutions

0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5-0.05

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

GlucoseLinear (Glucose)FructoseLinear (Fructose)SucroseLinear (Sucrose)

Concentartion in mM

Swel

ling

Rat

io

Behaviour of Hydrogel (20mol% PBA) in different concentration of Glucose, Fructose & Sucrose

0 1 2 3 4 5 6-0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

GlucoseSucroseFructose

Concentration in mM

swel

ling

Ratio

13

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Linear regression Analysis of Calibration Plots

Sugars R2 (1-5mM) Slope (Swelling ratio/[]

LOD (3σ/M) LOQ(10σ/M)

Fructose 0.9971 0.067 0.30 1.0

Glucose 0.9933 0.026 0.50 1.50

Sucrose 0.8661 0.003 2.20 7.22

0 1 2 3 4 5 6-0.1

0

0.1

0.2

0.3

0.4

GlucoseLinear (Glucose)FructoseLinear (Fructose)SucroseLinear (Sucrose)

Concentartion in mM

Swel

ling

Rat

io

Glucose in 20mol% & 5mol% PBA Hydrogel

0 5 10 15 20 250

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Glucose in 20mole%PBAGlucose in 5mole% PBA

concentration of Glucose in mM

Swel

ling

Ratio

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Conclusion

• Generally, the hydrogel shown a swelling in response to the Glucose and Fructose. But didn’t show a response to the sucrose.

• We have been particularly interested to create implantable glucose sensors that can potentially detect glucose concentrations within few minutes.

• For the best accurate measurement research being used to develop a Glucose gel sensor based on PBA chemistry to being measured using impedance.

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fixed voltage 20 mV frequency range 0.1 – 10 MHz

Solartron (Impedance)

0 5 10 15 20 25 30 35 40 45 500

1

2

3

4

5

C

(nF)

glucose concentration (mM)

1 kHz

Acrylamide20 mol % PBA1 mol % bisAm1mol % HMPP(1:1) water/DMSO

UV light30 minutes

Electrode Functionalisation with Hydrogel

Glucose Additions

Electrical Impedance Spectroscopy

The electrode was immersed in buffer solution (5mL

each electrical measurement was added 10 microliters of glucose (2.5M).

• an increase of concentration of glucose and increase of capacitance value.

• the change in structure of hydrogel cause changes in dieletric properties of the hydrogel. 18