AN OPTOFLUIDIC DIFFUSIVITY PROBE FOR REAL-TIME
CHEMICAL REACTION MONITORING
H. T. Zhao1, Y. Yang2, L. K. Chin1, W. M. Zhu1, Z. H. Yang3, H. X. Zhang3 and A. Q. Liu1†
1
School of Electrical & Electronic Engineering, Nanyang Technological University, Singapore 639798
2
School of Physics and Technology, Wuhan University, Wuhan 430072, China
3
Institute of Microelectronics, Peking University, Beijing 100871, China
ABSTRACT
This paper reports a novel optofluidic approach to monitor chemical reactions in real-time. This approach
is based on the fact that molecular size change in chemical reactions will lead to a change of the average
diffusion coefficient. Here we use the diffusivity change as an indicator to monitor the progress of chemical
reactions. The hydrolysis of maltose catalyzed by maltase is used as a demonstration. The results indicate
that the optimum condition for maltase is at pH 6.0 and 35℃. This approach can be used to reduce the cost
and simplify the procedure of reaction monitoring in chemical, pharmaceutical and process industries.
KEYWORDS: Chemical reaction monitor, Optofluidic, Diffusivity, Hydrolysis
INTRODUCTION
Microreactor technology is an efficient tool for chemical reactions such as synthesis and hydrolysis and
has great potential applications in chemical, pharmaceutical and process industries [1, 2]. However, there
is a continuous requirement in the integration of the analytical tools for fast and reliable process monitoring.
The conventional methods for chemical reaction monitoring include spectroscopy, photochemistry,
electrochemistry and so forth [3-5]. The spectroscopy approach analyzes the chemical composition at
different positions and hence determines the reaction rates. This approach is universal and can be applied
in many chemical reactions. However, it requires expensive and complicated detection setup, which is
difficult to be integrated in the lab-on-a-chip systems. The photochemistry and electrochemistry approaches
are chip compatible, but they are suffering from low-resolution problem.
In this paper, for the first time, chemical reactions are monitored in an optofluidic chip by determining
the average diffusivity of reaction products in real time. In the experiment, the hydrolysis of maltose
catalyzed by maltase is used as a demonstration.
WORKING PRINCIPLE
Figure 1 illustrates the working principle of the optofluidic probe. The microchip consists of a
microreactor and an optofluidic detecting region. In the microreactor, maltose solution (molar concentration:
1 mol/L) and maltase solution (mass concentration: 30 mg/mL) are injected into the reactor with the flow
rate ranging from 0.5 μL/min to 1 μL/min as shown in Fig. 1(a). The dimension of the microreactor is 5
mm (length) × 70 µm (width) ×120 µm (height). In the hydrolysis reaction, maltose molecule is catalyzed
by maltase and broken down into glucose molecules. The reaction time in the microreactor is around 10
seconds.
The products are then drawn into the optofluidic detecting region as the core stream, while deionized
water is injected as the cladding streams. From Stokes-Einstein equation, the diffusion coefficient of a
molecule is correlated to its molecular size. Here the diffusion coefficient of glucose (6.75×10-10 m2/s) is
three times faster than that of maltose (2.21×10-10 m2/s) as shown in Fig. 1(b). The diffusivity variation
leads to a less-contrast refractive index distribution and consequently a different light propagation pattern.
For example, the focal points move rightwards with the hydrolysis reaction as shown in Fig. 1(c). Based on
the light pattern, the diffusivity can be easily measured which is elaborated in previous work [6]. Therefore,
the chemical reactions can be monitored in real-time by probing the diffusivity change of the solution.
978-0-9798064-7-6/µTAS 2014/$20©14CBMS-0001 2110
18th International Conference on Miniaturized
Systems for Chemistry and Life Sciences
October 26-30, 2014, San Antonio, Texas, USA
Diffusion Coefficient
-10
2
(10 m /s)
Laser input
Maltose
Maltase
Maltose
88
x0 10
-10
0.4
0.8
1.6
Glucose
66
44
1.2
Maltose
2
21
1
0.8
0.6
0.4
0.8
0.6
0.4
Concentration
(mol/L)
Maltase
0.2
0.2
(b)
(i) w/o maltase
C12H22O11+H20
Maltase
(ii) w/ maltase
2∙C6H12O6
(Maltose)
(Glucose)
Light propagation pattern
Refractive index profile
(c)
(a)
Figure 1: Working principle of the proposed optofluidic probe for chemical reaction monitoring. (a) Schematic of
the optofluidic microchip, (b)the diffusion coefficient of maltose and glucose as a function of concentration, and (c)
refractive index profile and light propagation pattern (i) without and (ii) with hydrolysis reaction.
RESULTS AND DISCUSSIONS
Figure 2 shows the measured light propagation patterns without and with 10 mg/mL of maltase at pH
7.0 and 25℃. The maltase and maltose are injected at 0.5 μL/min, while the cladding streams are flowing
at 1 μL/min. Figure 3 shows the light intensity profile along the central line of the microchannel. The focal
points moves rightwards when maltase are added. Based on the previous work [6], the average diffusion
coefficients with and without maltase are determined to be 2.1 and 5.2 ×10-10 m2/s, respectively. In order to
quantify the percentage of reaction, the diffusivity of prescribed solutions are measured with different compositions. Figure 4 shows that the percentages of hydrolyzed maltose are linearly proportional to the measured diffusivity.
Without maltase
10 mg/mL
∆1
∆2
∆3
With maltase
Maltase: 10 mg/mL
Figure 2: Light propagation pattern without and with
10 mg/mL of maltase, respectively.
Light Intensity (a.u.)
1.1
∆1
0 mg/mL
∆2
∆3
0.9
0.7
0.5
0
0.4
0.6
0.8
1
Normalized Position
Figure 3: Normalized light intensity along the central
line of the microchannel.
2111
0.2
Figure 4: Relationship between the percentages of hydrolyzed maltose and measured average diffusivity.
Figure 5: Effects of temperature and pH on the hydrolysis reaction of maltose.
Figure 5 shows the influence of different temperature and pH values on the hydrolysis speed of maltose.
The maximum hydrolysis of 71.8% maltose occurs at 35℃, then the reaction abruptly declines with further
increment of temperature (pH is maintained at 7.0). On the other hand, the reaction reaches a maximum
percentage of 78.1% at pH 6.0 and 35℃, which indicates the optimum temperature and pH value.
CONCLUSIONS
In conclusion, an optofluidic diffusivity probe is designed and developed for chemical reaction monitoring in real-time. The hydrolysis of maltose is successfully demonstrated with the proposed method. The
results indicate that the optimum condition for maltase is at pH 6.0 and 35℃. The proposed method can be
used to reduce the cost and simplify the procedure of reaction monitoring in chemical, pharmaceutical and
process industries.
ACKNOWLEDGEMENT
This work is supported by the Environmental and Water Industry Development Council of Singapore
(Research project Grant No. 1102-IRIS-05-04).
REFERENCES
[1] Roberge, D.M., et al., “Microreactor technology: A revolution for the fine chemical and pharmaceutical
industries”, Chemical Engineering & Technology, 28(3), 318-323, 2005.
[2] Mason, B.P., et al., Greener approaches to organic synthesis using microreactor technology. Chemical
Reviews, 107(6), 2300-2318, 2007.
[3] Gitlin, L., et al., “Micro flow reactor chips with integrated luminescent chemosensors for spatially resolved on-line chemical reaction monitoring”, Lab on a Chip, 13(20), 4134-4141, 2013.
[4] Kamaruddin, M.J., et al., “Continuous and direct 'in situ' reaction monitoring of chemical reactions via
dielectric property measurement: controlled polymerization”, Rsc Advances, 4(11), 5709-5717, 2014.
[5] Yue, J., J.C. Schouten, and T.A. Nijhuis, “Integration of Microreactors with Spectroscopic Detection
for Online Reaction Monitoring and Catalyst Characterization”, Industrial & Engineering Chemistry
Research, 51(45), 14583-14609, 2012.
[6] H. T. Zhao, Y.Y., L. K. Chin and A. Q. Liu, “Diffusion coefficient measurement based on diffusioninduced focusing in optofluidic waveguide”, μTAS2014, 1532-1534, Freiburg, Germany.
CONTACT
†
A. Q. Liu; phone: +65-6790 4336; [email protected]
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