Principles around Accurate Blood Volume ... - ACS Publications

Nov 21, 2017 - Australian Centre for Research on Separation Science, School of Physical Sciences, University of Tasmania, Private Bag 75, Hobart,...
3 downloads 0 Views 1MB Size
Article Cite This: Langmuir 2017, 33, 14220−14225

pubs.acs.org/Langmuir

Principles around Accurate Blood Volume Collection Using Capillary Action Florian Lapierre,*,†,‡ Andrew Gooley,†,§ and Michael Breadmore†,‡ †

ASTech, ARCTraining Centre for Portable Analytical Separation Technologies, University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia ‡ Australian Centre for Research on Separation Science, School of Physical Sciences, University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia § Trajan Scientific and Medical, 7 Argent Place, Ringwood, Victoria 3134, Australia S Supporting Information *

ABSTRACT: Capillary action is one mechanism microfluidics uses to draw liquid autonomously in a substrate without the need of external energy. This behavior can be exploited to collect accurate volumes of liquids such as blood in narrow columns known as capillary tubes and help the development of inexpensive, user-friendly personalized biomedical tools. Precision bore glass capillaries demonstrate the “state of the art” for volume accuracy and precision, but height and radius must be carefully chosen in order to exploit the capillary action behavior efficiently. This Article investigates the influence of surface glass aging, due to prolonged exposure to humid air, and hematocrit level on the blood capillary rise. It provides also the tools to correctly define the optimum capillary dimensions to collect an accurate volume of blood in a glass capillary tube.



INTRODUCTION Affordable health care is one of the most significant problems facing both developed and developing countries around the world today. The significant drive toward improved health care in the next few decades will rely extensively on personalized medicine which by its very nature will require the collection and rapid analysis of individual samples with regularity, at a cost that is affordable, and with simplicity to be operated by untrained users.1,2 The development of inexpensive, easy to use personalized diagnostic tools is a challenge ideally addressed by microfluidic technology platforms.3 Microfluidics offers the advantages of using small volumes of sample and reagent, faster processing, and the ability to integrate multiple chemical and biochemical processes in a single device for ease of automation and user-friendliness, allowing widespread use. However, while the literature and market seem to focus mainly on how to process these liquids efficiently for analysis,4 there has been little focus on how to collect a volume of fluid with high precision and accuracy; a critical aspect to perform quantitative analysis of drugs/biomarkers in small liquid samples (i.e., using LC-MS). A few tools have been developed (i.e., syringes, pipettes) that are omnipresent for larger volumes (10 μL or greater), but the collection of smaller volumes has so far been restricted to laboratory settings with equipment operated by experienced users. © 2017 American Chemical Society

One microfluidic solution that can provide a simple way to collect fluid relies on the use of “capillary driven flow” or “capillary action”. Capillary action is defined by the movement of fluid via surface tension and adhesive forces and is easily seen when handling blotting paper.5 The same mechanism also applies in narrow columns, namely capillaries, where the surface tension force is greater than the gravitational and viscous forces hereby filling the capillary tube with the solution without the use of pumps or any other external energy.6 The process is entirely autonomous, relies only on the properties of the liquid, surface and size of the capillary, is spontaneous and works with any inclination of the capillary. The volume collected is defined by the capillary dimensions, and it does not overfill. Thus, when the capillary tube is filled with the liquid from one edge to another, the filling stops automatically, leaving the desired volume of fluid inside the capillary tube. The accuracy and precision of the volume collected is therefore defined by the tolerances with which the precision bore capillary can be made. Capillaries solely dependent on capillary action for filling are not commonly used for blood collection and most phlebotomists generally collect blood with capillary tubes which do not Received: August 13, 2017 Revised: September 26, 2017 Published: November 21, 2017 14220

DOI: 10.1021/acs.langmuir.7b02825 Langmuir 2017, 33, 14220−14225

Article

Langmuir

Therefore, from this equation, knowing the dimension of the capillary tube, the liquid characteristics, and the contact angle, it is possible to predict whether a narrow column can be completely filled with the desired liquid, as well as the time required to fill. Conversely, knowing the capillary dimensions and fluid properties, it is possible to determine the contact angle by measuring the time required to fill the column.14

rely on such behavior. The consequence of using capillaries not optimized for capillary action collection, is that the phlebotomist needs to negatively incline the capillary tube to enable the blood to flow into it. Breaking the contact between blood and the capillary for an instant increases the risk of introducing an air bubble inside the capillary, leading to inaccurate volume blood collection. With such problems, it is impossible to rely on the inexperienced patient being able to collect the blood sample themselves and guarantee the quality of the sample. However, precision glass capillaries have the capability of collecting fixed accurate volumes of liquid (up to 99.5% for the commercially available Vitrex capillary) via capillary action with very high precision (%RSD < 0.75%) from one edge of the tube to the other. Nevertheless, there is a requirement to determine the appropriate dimension. One limitation of such technology is that one capillary can collect only one defined volume of liquid. Such performance has not been overcome by any other laboratory technologies (i.e., pipet) and a precision bore glass capillary represents today the state-of-the-art for precision liquid collection. This work examines the limit and influence of surface and blood properties on the volume of blood that can be accurately collected through capillary action.





Blood Preparation (with Different Hematocrit Levels). Capillary blood was collected from a healthy male volunteer using a standard finger lancet blood collection protocol: the puncture site was cleaned with an isopropanol wipe and allowed to dry. A lancing device (UniStik3, Owen Mumford, UK) pricked the finger, and the first expressed volume of blood (∼30 μL) was removed. The finger was then gently massaged to promote blood flow and to collect up to 500 μL of blood into an EDTA coated tube (BD Microtainer K2E tubes). Hematocrit (HCT) level was adjusted from 35% to 53% by the addition or withdraw of the plasma fraction in whole blood. A blood sample was centrifuged at 10 000g for 2 min and a volume of plasma (upper fraction) was collected and redistributed to other blood samples, thus increasing or reducing the red blood cell concentration. Each sample was assessed using the hemoCue Hb 201+ System (hemoCue AB, SE) and samples of blood were used within 1 h. The volunteer signed a consent form stating their understanding of the experiment and protecting their privacy. Ethical approval was given by ethical committee at the University of Tasmania (application number: H0015476) and any remaining blood volume was safely discarded. Borosilicate Glass Capillaries. Precision bore borosilicate glass capillaries with a hydrolytic resistance Class HGB1 (intended for pharmaceutical use) were purchased from Vitrex with a fixed volume of 3 μL. The inner radius was measured at 181 μm ± 0.005 μm with an average height of 28.977 mm ± 0.047 μm (%RSD = 0.16%). A dual dye ratiometric photometry volume measurement system (VMS, Artel NH) was used to validate the volume of fluid collected. Volumes were measured at 2.994 μL ± 0.020 μL (accuracy = 99.81%) with a %RSD of 0.68% (see Supporting Information Table S1) and are in correlation with the manufacturer’s specification. These high quality medical tubes are inert and specialized for the handling and transporting of liquids while preserving their intrinsic integrity. Cover Glass. Borosilicate coverslips with the same hydrolytic resistance Class HGB1 to the capillary tubes were provided by Trajan Scientific & Medical. Contact angle measurements with 5 μL of blood (HCT measured at 44%) were performed on the coverslip before the annealing process, and after being exposed to humid air for a defined time (0−4320 min). Annealing Process. Capillaries and coverslips were annealed with a ramping temperature up to 600 °C for 30 min and slowly cooled down to room temperature for another 30 min. Following the annealing process, the capillaries and coverslips were stored in a tropical aluminum packaging containing desiccant. The latter avoids moisture accumulation on the glass surface and light exposure from the environment. It is to be noted that no washing steps were performed at any time. The capillary tubes used in this study are certified high quality medical tubes for handling and transporting fluids. Exposure Time. After the annealing process, sets of capillaries and coverslips were left in an air-conditioned room with relative humidity (RH) and temperature set at 45% and 23 °C, respectively. Capillaries were then used for blood collection at defined times (0−4470 min). Capillary Blood Collection. For each blood sample at a defined HCT level and each capillary exposure time, 10 capillaries were used for collection. The capillaries were held in a vertical position against gravity on a custom-made X-Y-Z stage incorporating a support with engraved grooves ensuring the vertical inclination of the capillary tubes. The collection of blood from the bottom edge to the top was performed by bringing a volume of blood at the vicinity of the lower edge of each capillary tube. A video camera recorded the filling of the 10 capillaries at 24 frames per second (see Video S1).

THEORY

The dynamics of capillary flow has been studied since the 17th century and is applied in a myriad of applications, especially in the medical field.7 The most common law describing capillary action in a cylindrical tube is defined by eq 1.8 The height h reached by the liquid via capillary action is dependent on the liquid−air surface tension γ, the contact angle θ between the liquid and the surface of the tube, the density ρ of the liquid, the local acceleration g due to gravity and the radius r of the capillary tube. Thus, for a column of a specified radius, there is a limit to the height with which it can be filled, which in turn through eq 2 defines the volume V of fluid collected inside the cylindrical capillary tube.

h=

2γ cos θ ρgr

(1)

V = πr 2h

(2)

Equation 1 shows that the capillary rise is dependent on the fluid properties and on the surface chemistry of the capillary bore. The capillary action is therefore limited to a range of capillary dimensions for specific liquids and capillary material properties; in other words, the liquid to be collected and the nature of the capillary will influence the volume of liquid collected. To understand this limitation, the Washburn−Lucas equation was developed in 1921.9 The equation describes the capillary flow of Newtonian liquids in cylindrical tubes to determine the distance traveled by a liquid in a narrow column via capillary action over time.10 The Washburn equation 3 is defined as

⎡h ⎛ h ⎞⎤ ⎟⎥ t(h) = − T ⎢ + cos θ ln⎜1 − ⎝ ⎣L L cos θ ⎠⎦ where L =

2γ ρgr

and T =

16γη ρ2 g 2r 3

METHODS

(3)

are characteristic length and time scales

that depend on the radius r of the capillary and on the liquid properties (viscosity η, density ρ, and surface tension γ), and t(h), the time to fill the capillary to height h.11 Even though the law is based on Newtonian liquids, recent publications have validated such law for non-Newtonian liquids such as blood for specific conditions. Indeed, whole blood exhibits a Newtonian behavior with a constant viscosity at high shear stress, i.e., when the blood flows rapidly into a tube, and blood capillary rise was well predicted through the use of such law.12,13 14221

DOI: 10.1021/acs.langmuir.7b02825 Langmuir 2017, 33, 14220−14225

Article

Langmuir

Figure 1. (a) Picture from the video source at 24 frames per second. Ten capillaries (h = 29 mm, r = 0.181 μm) are held vertically. EDTA blood contained in an Eppendorf vial is brought in contact with the bottom edge of the capillary tube until the capillary is filled with blood. (b) Time space plot of the filling of one capillary. The arrow points from the original frame to the corresponding time space plot location. (c) Resulting image after red color threshold and edge detection. X- and Y-axes are converted from pixels to seconds and millimeters, respectively.

kg·m−3,17 and the surface tension is at γ = 0.058 N/m.18 The yellow dotted line in Figure 2 corresponds to the capillary

Video Processing. Using ImageJ software, the video of four capillaries was processed with the following procedure: a line was drawn inside the capillary where the blood flowed via capillary action (Figure 1a). This line represents the length of the capillary tube (h = 28.977 mm) from one edge to the other. Using the “reslice” function, a time space plot image was generated (Figure 1b). This image illustrates the position of the blood inside the capillary (Y-axis) in time (X-axis). By adjusting the color threshold, the edge detection of the interface blood/air in the capillary can be extrapolated (Figure 1c). The image was finally converted as XY coordinates where Y-axis is equal to the length of the capillary (h = 28.977 mm) and X-axis to the time (1 pixel = 41.708 ms).



RESULTS AND DISCUSSION Capillary Action Model. The purpose of this article is to give the reader the tools to choose the optimum capillary dimensions for collecting accurately a defined microvolume of liquid (e.g., blood) via capillary action. We have correlated the study based on the theoretical and experimental analysis of precision bore borosilicate glass capillaries (exposed to humid air for a defined time) with blood (at different HCT level) using contact angle measurements and capillary rise behavior. A preliminary study explored the significance of borosilicate glass exposure to humid air as determined by contact angle measurements using glass coverslips with 5 μL drops of whole blood at constant HCT. Annealed coverslips exposed to a clean humid environment showed an increase in contact angle, modulating from ∼10° (annealed coverslip) to 36° within 72 h. The contact angle was measured at 70° for the nonannealed coverslip (see Table S2 in the Supporting Information). This indicates that there is an aging process of the borosilicate glass surface chemistry which depends on its storage condition, and most likely its humidity environment.15,16 Moreover, the minimum contact angle of whole blood with annealed borosilicate glass never reaches values below 6°; no superhydrophilic behavior was observed. No hydrophobic behavior (≥90°) was measured either with exposed borosilicate glass and whole blood. This means that borosilicate glass will neither exhibit a behavior where it absorbs completely the total volume of blood on its surface nor repel the water molecules in such a case that the capillary action would not operate. These defining contact angles were inserted in the capillary action eq 1 to predict the possible capillary tube radius and height where capillary action would overcome gravitational force. For blood, the average density is estimated at ρ = 1060

Figure 2. Limit of capillary tube diameter and height modeled with the capillary action eq 1 for contact angle between blood and borosilicate glass of 10° (yellow dot line) and 70° (green dot line). The blue dash line represents the possible dimensions for a fixed volume of 3 μL. The bold section of the line represents the possible dimensions of a 3 μL capillary when the contact angle between blood and borosilicate reaches its maximum value of 70°; h70 and 2r70 are the maximum height and minimum diameter at such condition. The red dots represent the defined capillary tubes provided by Vitrex with volumes of 3, 5, and 10 μL. Each dot intersects the capillary action eq 1 when θ = 61.5° (3 μL), θ = 52.5° (5 μL), and θ = 30.5° (10 μL).

height and radius that can be filled by capillary action when the contact angle between blood and borosilicate glass is 10°. All the dimensions below this curve can be filled via capillary action if the contact angle stays at 10°. Following the same principle, the green dotted line represents the capillary dimension limit when the contact angle is 70°. Again, all the dimension below this curve enable capillary action when the contact angle is of 70°. From these curves, there exists a range of diameters and heights where the capillary force overcomes gravitational force, and where the defined capillary tube will be entirely filled. For instance, the blue dash line represents all the capillary 14222

DOI: 10.1021/acs.langmuir.7b02825 Langmuir 2017, 33, 14220−14225

Article

Langmuir dimensions that will give a fixed volume of 3 μL. The intersection of the blue line with that calculated with a contact angle of 70° defines the maximum height (h70 = 15.2 mm) and minimum diameter (2r70 = 0.502 mm) that can be filled by capillary action under these conditions (bold section of the blue dash line). If the height of the capillary is larger than 15.2 mm, then the capillary will not completely fill and the volume will not be accurately collected. Following the same reasoning, if the contact angle between blood and borosilicate is only 10°, the maximum capillary height of h10 = 126.3 mm and minimum diameter of r10 = 0.087 mm are calculated. The same logic can be applied for volumes of 5 and 10 μL, with the calculated results summarized in Table 1.

This can be estimated from the Lucas−Washburn equation which characterizes the height h traveled by a liquid, in this study, blood, via capillary action for a given time t. Figure 3

Table 1. Maximum Capillary Height and Minimum Capillary Diameter for Their CorrEsponding Volumes When the Contact Angle between Blood and Borosilicate Glass Is Maximum at 70° and Minimum at 10°a θ = 70°

θ = 10°

volume (μL)

h70 (mm)

2r70 (mm)

h10 (mm)

2r10 (mm)

3

15.2

0.502

126.3

0.174

5

9.1

0.836

75.8

0.290

10

4.5

1.682

37.9

0.580

Vitrex capillary hcap = 29 mm, 2rcap = 0.363 mm hcap = 29 mm, 2rcap = 0.468 mm hcap = 29 mm, 2rcap = 0.663 mm

θmax (deg)

Figure 3. Whole blood at HCT 35% capillary rise (height) versus time for 3 μL volume borosilicate tube (h = 29 mm, r = 0.181 μm) with (black square) 0 min, (red circle) 240 min, (blue triangle) 360 min, and (pink triangle) 480 min exposure to humid environment (RH @ 45%). Dashed lines correspond to the Washburn equation fitting of the experimental data to extrapolate the resulting contact angle between blood and the borosilicate bore (R2 > 0.9). The contact angle increases with the increasing exposure time to humid air.

61.5 52.5 30.5

a Using the Vitrex capillaries, the capillary tube dimensions are fixed for each volume and the maximum contact angle between blood and borosilicate θmax can be estimated. If the contact angle between blood and borosilicate glass goes beyond that value, the capillary action is overcome by gravitational force and the capillary tube will not be filled entirely, losing its volume accuracy capability.

shows the distance traveled by blood in time inside borosilicate capillaries exposed for different periods of time to humid air, and of h = 29 mm and 2r = 0.363 mm (V = 3 μL). For the black square values, the capillary tube was freshly annealed while for the red circle, blue triangle and purple triangle, the filling measurements were performed 240, 360, and 480 min after the annealing process. It is to be noted that the same source of blood (hematocrit level measured at 35%) was used for each of these experiments. The Washburn equation was then fitted on each curve by setting the viscosity at 0.0035 Pa·s, the density of blood (HCT 35%) at 1044.3 kg·m−3,17 the surface tension at 0.058 N/m, and radius at 0.181 mm. The resulting contact angle for each experimental data was then calculated from the fitted curves. The coefficient of regression R2 is modulating between 0.95 and 0.99 showing good correlation between experimental data and the Washburn equation. It is clear from these data that the speed at which the capillary tube is filled decreases with the time of capillary exposition to air and humidity, taking 1.2 s with dry/fresh capillary to 2.6 s after 480 min exposition to humid air. Given that the same source of blood was used with constant HCT, this reflects a change in contact angle. From a freshly annealed capillary tube, the contact angle is estimated at 33.62° and increases up to 52.26° after exposition to humid air for 480 min. In order to understand the impact of blood HCT level, contact angle and time to fill the 3 μL capillary tubes was measured by modulating the HCT concentration from 35% to 53% (see Table S3 for corresponding blood physical properties) and exposition to humid environment from 0 to 4470 min. Figure 4 compares the experimental data (red square) of capillary filling time and contact angle with the theoretical Washburn eq 3 (black dash line) given for a 3 μL borosilicate capillary tube with h = 29 mm and r = 0.181 mm. From the theoretical curve, one can notice that, for contact angle below

Alternatively, eq 1 can also be used to determine the maximum contact angle θmax until which the capillary force will not be sufficient to fill a defined capillary tube entirely with blood. For instance, Vitrex borosilicate capillaries have defined height and radius with their respective volume of 3, 5, 10 μL, and represented as a red dot in Figure 2 and in Table 1. θmax is estimated from eq 1 at 61.5° for a 3 μL volume capacity, 50.5° and 30.5° for volumes of 5 and 10 μL, respectively. These contact angles are all below the maximum contact angle measured between blood and borosilicate glass θ = 70°. This means that there exist some conditions where the blood will not fill entirely the capillary tube with capillary action. In other words, if the contact angle between blood and the bore of the capillary passes beyond the limit value θmax, then, the capillary tube will not be able to be filled entirely and the volume accuracy of blood collection will be lost. Knowing that the maximum contact angle between blood and borosilicate glass is 70°, the range of capillary dimensions for which a volume of 3 μL can be accurately collected is h ≤ 15.2 mm and with a radius of ≥0.502 mm. Capillary height and radius for 5 and 10 μL volumes are summarized in Table 1. With capillaries of these dimensions, theoretically, no matter the condition of storage of the borosilicate glass, the capillary action will always be effective and the entire volume will be filled with blood. Washburn Model and Experimental Data. The capillary action model described above provides whether or not the volume can be collected, but not the time required to do so. 14223

DOI: 10.1021/acs.langmuir.7b02825 Langmuir 2017, 33, 14220−14225

Article

Langmuir

Knowing that the contact angle between different sources of blood and borosilicate glass modulates from 30° to ∼60°, the 5 μL volume Vitrex capillary tube can only be filled when the contact angle is below 52.5° (purple dash line in Figure 4). Hence, only 54% of the experimental hematocrit and capillary combinations will fill this volume. For the 10 μL Vitrex capillary tube (green dash line), only a freshly annealed capillary tube sampled with low HCT blood can entirely fill the capillary. From a practical perspective, knowing that the surface chemistry of the glass capillary can change over time, it is possible to select the optimum capillary height and diameter in order to collect a desired volume of blood accurately−even in the worst storage condition. For instance, by selecting a capillary of height of 15.2 mm and diameter of 0.502 mm for a total volume of 3 μL, even with a 70° contact angle, the capillary action will be effective. Based on the Washburn equation, it would take 0.148 s to fill the capillary entirely with a contact angle of 10° with blood while it would take 5.925 s at 70°, thus providing robust conditions under which an accurate volume of blood can be collected quickly by capillary action.

Figure 4. Experimental data (squares) of contact angle θ and filling time t for different time of exposure to humid air (gradient of red) and HCT levels with the corresponding theoretical prediction (black dash line) for a capillary tube of 3 μL (r = 0.181 mm, h = 29 mm) from eq 3. The limit at 61.5° is also predicted from the Washburn equation with such capillary. Purple and green dash lines correspond to the theoretical predictions from eq 3 for capillary tubes of volumes 5 and 10 μL, respectively. Limits at 52.5° and 30.5° are also calculated from such glass capillary dimensions with whole blood.



CONCLUSION

Capillary action is a simple approach for the collection of small volumes of liquid that can bring effortless and accurate blood collection directly to the patient. However, capillary action must come with the understanding of its advantages (i.e., no generation of air bubble, fast, no external energy required) and limitations (i.e., small volumes, limited dimensions, liquids and surface chemistry) in order to develop the adequate tool. In this Article, we show through theoretical models and experimental data that capillary action is dependent on the liquids used and the properties of the capillary (i.e., dimension, and nature of material). The annealing process of the borosilicate glass resets the surface chemistry to its original state and the use of tropical packaging (i.e., aluminum container with desiccant cap) enables the storage of the capillaries for months without affecting the glass surface chemistry. Keeping the glass in its natural inert state is primordial to preserve the intrinsic quality of the collected sample for clinical analysis. We have shown that blood exhibits Newtonian behavior when filling the capillary and that this behavior and affirmations are in correlation with models and experiments found in the literature. This study also shows that the surface chemistry of borosilicate glass changes when exposed to a humid environment. We also showed that a greater HCT level in blood leads to greater contact angle in the capillary, limiting the capillary action behavior. Based on the capillary and Lucas−Washburn equations, it is possible to predict the behavior of liquids such as blood in defined capillary tubes and calculate the optimum capillary height and radius to enable the collection of 3, 5, and 10 μL of blood in any situation, by anyone. The integration of these capillaries in an embodiment such as the hemaPEN will enable blood microsampling from finger prick. The accuracy of blood volume is defined by the quality of the glass capillary and its dimension, and blood collection should be totally independent of the user. Blood collection would happen within seconds while avoiding the generation of air bubbles during the collection.

30°, the time to fill the capillary is stabilized at around 1 s. However, from contact angle greater that 55°, the time to fill the capillary is greater than 2.5 s. This means that for the latter range, a small change in contact angle will result in a large change in the filling time, which will extend even further as the contact angle gets closer to 61.5°. Beyond this contact angle, the 3 μL capillary tube cannot be filled entirely. Also, the model and experimental data show that if the time to fill the capillary tube is greater than 12.05 s, then the capillary is not entirely filled. If the contact angle between blood and the glass surface increases beyond 61.5°, then the capillary tube will never fill entirely. This was experimentally verified using capillaries left 6 months after annealing (contact angle of 64.69°), and the blood reached a maximum height of 27 mm in 16 s ± 4 s. This is less than the full height of 29 mm, preventing the complete filling of the capillary. Theoretical curves for volumes of 5 μL (purple dash line) and 10 μL (green dash line) show the same behavior while their limits are estimated at 52.5° and 30.5°, identical to that predicted by the capillary action eq 1. Experimental data (22 different conditions of HCT level and exposure time, repeated 4 times) fits with the theoretical Washburn−Lucas curve. Comparing the different hematocrit samples, the contact angle and filling time increase with the increasing HCT level. Moreover, for low HCT level and low exposure time, the standard deviation is greater on the contact angle than on the filling time, while for high HCT level and long exposure time, the standard deviation is greater on the filling time than on the contact angle. This behavior is in correlation with the theoretical curve where a small change in the filling time implies a large contact angle variation in the 0− 30° contact angle zone. On the contrary, in the 55−61.5° contact angle zone, a small change in contact angle variation implies larger filling time variation. In both cases, the Washburn equation’s prediction is accurate with experimental data and that the filling time depends on both the aging time of the capillary, as well as the HCT level in the sample. 14224

DOI: 10.1021/acs.langmuir.7b02825 Langmuir 2017, 33, 14220−14225

Article

Langmuir



(14) Heshmati, M.; Piri, M. Experimental Investigation of Dynamic Contact Angle and Capillary Rise in Tubes with Circular and Noncircular Cross Sections. Langmuir 2014, 30 (47), 14151−14162. (15) Barthel, A. J.; Kim, S. H. Surface Chemistry Dependence of Water Adsorption on Solid Substrates in Humid Ambient and Humidity Effects on Wear of Copper and Glass Surfaces. Tribol.Mater., Surf. Interfaces 2013, 7 (2), 63−68. (16) Bernett, M. K.; Zisman, W. A. Effect of Adsorbed Water on Wetting Properties of Borosilicate Glass, Quartz, and Sapphire. J. Colloid Interface Sci. 1969, 29 (3), 413−423. (17) Kenner, T. The Measurement of Blood Density and Its Meaning. Basic Res. Cardiol. 1989, 84 (2), 111−124. (18) Hrncír, E.; Rosina, J. Surface Tension of Blood. Physiol. Res. 1997, 46 (4), 319−321.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.langmuir.7b02825. Volumetric measurements of eight 3 μL capillaries; contact angle of whole blood (HCT 44%) with borosilicate cover slip in time after the annealing process; physical properties of blood at different HCT levels (PDF) Video of 10 borosilicate capillary tubes filling with whole blood (AVI)



AUTHOR INFORMATION

ORCID

Florian Lapierre: 0000-0003-0377-6069 Notes

The authors declare no competing financial interest.



ACKNOWLEDGMENTS The authors thank Trajan Scientific and Medical for providing technical support. The authors would like to acknowledge funding from the Australian Research Council through the Training Centre for Portable Analytical Separation Technologies (IC140100022). M.B. is the recipient of an ARC Future Fellowship (FT130100101).



REFERENCES

(1) Martinez, A. W.; Phillips, S. T.; Whitesides, G. M.; Carrilho, E. Diagnostics for the Developing World: Microfluidic Paper-Based Analytical Devices. Anal. Chem. 2010, 82 (1), 3−10. (2) Chin, C. D.; Linder, V.; Sia, S. K. Commercialization of Microfluidic Point-of-Care Diagnostic Devices. Lab Chip 2012, 12 (12), 2118−2134. (3) Microfluidics for Medical Applications; Nanoscience & Nanotechnology Series; van den Berg, A., Segerink, L., Eds.; Royal Society of Chemistry: 2014; DOI: 10.1039/9781849737593. (4) da Silva, E. T.; Souto, D. E.; Barragan, J. T.; de F. Giarola, J.; de Moraes, A. C.; Kubota, L. T. Electrochemical Biosensors in Point-ofCare Devices: Recent Advances and Future Trends. ChemElectroChem 2017, 4, 778−794. (5) Yetisen, A. K.; Akram, M. S.; Lowe, C. R. Paper-Based Microfluidic Point-of-Care Diagnostic Devices. Lab Chip 2013, 13 (12), 2210−2251. (6) Stange, M.; Dreyer, M.; Rath, H. Capillary Driven Flow in Circular Cylindrical Tubes. Phys. Fluids 2003, 15 (9), 2587−2601. (7) Atencia, J.; Beebe, D. J. Controlled Microfluidic Interfaces. Nature 2005, 437 (7059), 648−655. (8) Batchelor, G. K. An Introduction to Fluid Dynamics; Cambridge University Press, 2000. (9) Washburn, E. W. The Dynamics of Capillary Flow. Phys. Rev. 1921, 17 (3), 273−283. (10) Zhmud, B. V.; Tiberg, F.; Hallstensson, K. Dynamics of Capillary Rise. J. Colloid Interface Sci. 2000, 228 (2), 263−269. (11) O’Loughlin, M.; Wilk, K.; Priest, C.; Ralston, J.; Popescu, M. N. Capillary Rise Dynamics of Aqueous Glycerol Solutions in Glass Capillaries: A Critical Examination of the Washburn Equation. J. Colloid Interface Sci. 2013, 411, 257−264. (12) Kar, S.; Dash, M.; Maiti, T. K.; Chakraborty, S. Effect of Hematocrit on Blood Dynamics on a Compact Disc Platform. Analyst 2015, 140 (5), 1432−1437. (13) Gosselin, D.; Huet, M.; Cubizolles, M.; Rabaud, D.; Belgacem, N.; Chaussy, D.; Berthier, J. 1 Univ. Grenoble Alpes, F-38000 Grenoble, France. Viscoelastic Capillary Flow: The Case of Whole Blood. AIMS Biophys. 2016, 3 (3), 340−357. 14225

DOI: 10.1021/acs.langmuir.7b02825 Langmuir 2017, 33, 14220−14225