Single-Shot Detection of Neurotransmitters in Whole-Blood Samples by Means of the Heat-Transfer Method in Combination with Synthetic Receptors
<p>Schematic design of the four-chamber heat-transfer method (HTM) setup: (<b>Left panel</b>) overview: the sensor chip (<b>1</b>) was placed on a copper lid (<b>2</b>), which was used as a heat sink. The central cavity in the copper lid is intended to install a thermocouple (<b>3</b>). The assembly is heated by power resistor (<b>4</b>). (<b>Right panel</b>) top view: the sensor was divided into four triangular shaped identical sections of 10 mm<sup>2</sup> (<b>5</b>) with a height of 1 mm by means of a polydimethylsiloxane (PDMS) flow cell. Each flow cell connects to two Teflon tubes serving as fluid in- and outlet (<b>6</b>) and thermocouple holders (<b>7</b>), respectively. An alternative 2D representation of the setup can be found in [<a href="#B22-sensors-17-02701" class="html-bibr">22</a>].</p> "> Figure 2
<p>Single-shot measurement setup (<b>a</b>) Front view: consists of: a heater module, a selective deposited molecularly imprinted polymer (MIP) layer on an aluminum substrate, a PDMS flow cell and 3 temperature sensors which is here shown as a cross section of the finished flow cell. (<b>b</b>) The flow cell occupies a total area of 30 × 30 mm<sup>2</sup> and contains one centralized inlet (<b>1</b>), two parallel sensing areas of 9 mm<sup>2</sup> each (<b>2</b>) with integrated thermocouples (<b>3</b>) and a pumping area (<b>4</b>). The volumetric flow rate of the sample fluid can be controlled by changing the width of the channel in position (<b>5</b>). (<b>c</b>) The height of the flow cell is 0.6 mm, and the vertical pump is 8 mm high. Whole blood samples can be added to the inlet. The measurements can be carried out as single-shot, without a stabilization step in buffer solution.</p> "> Figure 2 Cont.
<p>Single-shot measurement setup (<b>a</b>) Front view: consists of: a heater module, a selective deposited molecularly imprinted polymer (MIP) layer on an aluminum substrate, a PDMS flow cell and 3 temperature sensors which is here shown as a cross section of the finished flow cell. (<b>b</b>) The flow cell occupies a total area of 30 × 30 mm<sup>2</sup> and contains one centralized inlet (<b>1</b>), two parallel sensing areas of 9 mm<sup>2</sup> each (<b>2</b>) with integrated thermocouples (<b>3</b>) and a pumping area (<b>4</b>). The volumetric flow rate of the sample fluid can be controlled by changing the width of the channel in position (<b>5</b>). (<b>c</b>) The height of the flow cell is 0.6 mm, and the vertical pump is 8 mm high. Whole blood samples can be added to the inlet. The measurements can be carried out as single-shot, without a stabilization step in buffer solution.</p> "> Figure 3
<p>Scanning electron microscope (SEM) analysis of a MIP-coated aluminum chip (<b>left</b>) and a cross-section analysis of the same sample (<b>right</b>).</p> "> Figure 4
<p>Results obtained in a proof-of-principle experiment using the four-chamber HTM device (<b>a</b>) shows the temperatures <span class="html-italic">T</span><sub>1,2,3,4,5</sub> as function of time, (<b>b</b>) shows the corresponding time-dependent heat-transfer resistance. A concentration dependent effect on both the temperature and thermal resistance signal can clearly be observed.</p> "> Figure 5
<p>Dose-response curve obtained from the experiment described in <a href="#sensors-17-02701-f004" class="html-fig">Figure 4</a> (<b>black curve</b>), reference experiments on NIP-coated chips (<b>red curve</b>), and selectivity (<b>blue curve</b>).</p> "> Figure 6
<p>Results obtained using the single-shot device (<b>a</b>) 300 µL blood, spiked to a concentration of 1 µM of serotonin is added to the central cavity. An increase in temperature can be observed in both the NIP (<b>red curve</b>) and MIP (<b>black curve</b>) channel due to the medium change. The increase in the MIP is less pronounced as serotonin binds to the MIP, blocking the heat flow in the process, which is translated as a decrease in the differential signal (<b>blue curve</b>), (<b>b</b>) a similar experiment using an analogue—histamine—demonstrates a different behavior. Histamine does not bind to the MIP, and a small increase rather than a decrease in the differential signal can be observed.</p> "> Figure 6 Cont.
<p>Results obtained using the single-shot device (<b>a</b>) 300 µL blood, spiked to a concentration of 1 µM of serotonin is added to the central cavity. An increase in temperature can be observed in both the NIP (<b>red curve</b>) and MIP (<b>black curve</b>) channel due to the medium change. The increase in the MIP is less pronounced as serotonin binds to the MIP, blocking the heat flow in the process, which is translated as a decrease in the differential signal (<b>blue curve</b>), (<b>b</b>) a similar experiment using an analogue—histamine—demonstrates a different behavior. Histamine does not bind to the MIP, and a small increase rather than a decrease in the differential signal can be observed.</p> "> Figure 7
<p>Dose-response curve obtained by analyzing the response of single shot devices to whole blood samples spike with increasing concentrations of serotonin. The absolute change in the differential signal is presented in function of the spiking concentration. The red curve represents an allometric dose-response curve (R<sup>2</sup> = 0.996). These data indicate that it is possible to qualitatively detect fluctuations in the concentration of serotonin in whole blood samples.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Design of the Four Chamber-HTM Platform
2.2. Design of a Single-Shot Device
2.3. Receptor Layer
2.4. Proof-of-Principle Experiments in Whole Blood Samples
2.5. Single-Shot Serotonin Measurement in Whole Blood Samples
2.6. Optical Characterization
3. Results and Discussion
3.1. Proof-of-Principle: Thermal MIP-Based Detection of Serotonin in Whole Blood
3.2. Proof-of-Principle: Thermal MIP-Based Detection of Serotonin in Whole Blood
3.3. Single-Shot Detection of Serotonin in Whole Blood Samples
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Vandenryt, T.; Van Grinsven, B.; Eersels, K.; Cornelis, P.; Kholwadia, S.; Cleij, T.J.; Thoelen, R.; De Ceuninck, W.; Peeters, M.; Wagner, P. Single-Shot Detection of Neurotransmitters in Whole-Blood Samples by Means of the Heat-Transfer Method in Combination with Synthetic Receptors. Sensors 2017, 17, 2701. https://doi.org/10.3390/s17122701
Vandenryt T, Van Grinsven B, Eersels K, Cornelis P, Kholwadia S, Cleij TJ, Thoelen R, De Ceuninck W, Peeters M, Wagner P. Single-Shot Detection of Neurotransmitters in Whole-Blood Samples by Means of the Heat-Transfer Method in Combination with Synthetic Receptors. Sensors. 2017; 17(12):2701. https://doi.org/10.3390/s17122701
Chicago/Turabian StyleVandenryt, Thijs, Bart Van Grinsven, Kasper Eersels, Peter Cornelis, Safira Kholwadia, Thomas J. Cleij, Ronald Thoelen, Ward De Ceuninck, Marloes Peeters, and Patrick Wagner. 2017. "Single-Shot Detection of Neurotransmitters in Whole-Blood Samples by Means of the Heat-Transfer Method in Combination with Synthetic Receptors" Sensors 17, no. 12: 2701. https://doi.org/10.3390/s17122701