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Proposal of blood-collecting needle approach to semi-invasive method
Diabetes Research and Clinical Practice 66S (2004) S179–S183 www.elsevier.com/locate/diabres
Proposal of blood-collecting needle approach to semi-invasive method Masaki Yamaguchia,*, Yuji Kawabataa, Katsuya Yamazakib, Masashi Kobayashib, Takehito Itoc a
Department of Material Systems Engineering and Life Science, Faculty of Engineering, Toyama University, 3190 Gofuko, Toyama 930-8555, Japan b The First Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan c International Medical Division, Nipro Co., Osaka, Japan Received 14 July 2003; accepted 11 August 2003
Abstract Many diabetic patients carry a portable self-monitoring of blood glucose (SMBG)-analyzer in order to collect their own blood and examine their glucose levels; this allows them to determine such factors as insulin dose, diet and exercise to stay healthy. However, the test causes physical and mental stress for the subjects. The authors aim to develop a semi-invasive bloodcollecting needle which does not need a power source for the pump mechanism. In this study, we fabricated a capillary action needle that can collect the blood sample automatically. A blood-collecting needle was fabricated from 25 gage sized medical needle (diameter of 0.5 mm, stainless steel) by cutting process, and it had a half-opened crevice in the tip. In order to evaluate the physical characteristics of the blood-collecting needle, the relationship between the size and suction time and/or suction volume were measured using an isotonic sodium chloride solution, whole rabbit blood, and whole human blood with anticoagulant. Next, in order to evaluate the degree of invasion, the diameters of erythema in auricles of rabbits were observed for 2 days using a CCD camera-type microscope. The mean suction time of the isotonic sodium chloride solution and the whole rabbit blood were 1.5 s (n = 10) and 9.0 s (n = 5), respectively. Selection of a suitable size of the blood-collecting needle enabled the collection of 0.1 mL of whole human blood in 10 s. Moreover, it was shown, by comparing the observed diameter of the erythema, that the invasiveness of the blood-collecting needle was smaller than for commercial needles of the equal diameter. It became clear that this fulfils the fundamental functions of a semi-invasive blood-collecting needle. # 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Semi-invasive; Self-monitoring of blood glucose; Needle; Capillary action
1. Introduction * Corresponding author. Tel.: +81 76 445 6855; fax: +81 76 445 6855. E-mail address: [email protected] (M. Yamaguchi).
The total number of diabetic patients worldwide was estimated to be more than 150 million in
0168-8227/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2003.08.016
S180
M. Yamaguchi et al. / Diabetes Research and Clinical Practice 66S (2004) S179–S183
2000 [1]. Since, severe diabetic patients need a daily injection of insulin and daily blood collection for monitoring their blood glucose, better semi-invasive methods for blood collection urgently need to be developed. If the volume of collected blood could be reduced to approximately 0.1 mL, this could result in almost complete disappearance of the physical pain caused by needling. This would be good news for the diabetic patients who have to frequently collect their blood for monitoring blood glucose. However, as the inner width of collecting needles gets smaller, the viscous resistance increases due to increased friction caused by the inner wall of the needle and blood, resulting in difficulties in blood collection when a specific pumping device is not also used. Moreover, it is also known that too much negative pressure may modify the blood properties. Increased viscous resistance is a negative factor to the development of clinical blood glucose monitors, in a small, portable format. Thus, the development of blood collecting systems that mimic the blood-sucking device of the mosquito’s snout, which can penetrate human skins and suck up the blood, have long been investigated [2–5]. It is very important to develop a semi-invasive blood-collecting needle, which can automatically draw a small but sufficient amount of blood without requiring any pumping device, as they generally require a small power-source. We have developed a collecting needle, which automatically collects blood by capillary action. The fabricated needle had a halfopen trough formed at the pointed end. The driving force of the pump was caused by capillary action due to the intermolecular forces between the needle and the blood. In this study, we report the results regarding fabricated semi-invasive blood-collecting needles. In vitro physical properties of the semi-invasive bloodcollecting needles were evaluated using saline, rabbit and human whole blood. The physical properties investigated were the relationship between section shape and size of the needle, and the time and volume required for action. Then the in vivo properties were examined in order to evaluate the degree of invasiveness and irritation, by measuring the changes in diameter of the erythema made by puncturing rabbit ears.
2. Materials and methods 2.1. In vitro evaluation A semi-invasive blood-collecting needle was fabricated, which had a half-open trough at the pointed head of the needle. A stainless steel blood-collecting needle (SUS304) with gauge 25 (outer diameter 0.50 mm, the unit showing the width of the needle is defined as G below) was cut and processed with electrolytic grinding to create the semi-invasive blood-collecting needle (Fig. 1). In order to evaluate the relationship between the needle section shape and size and the time and volume required for action, 3 semi-invasive collecting needles (MI-1–MI-3) were fabricated that had the same cross-sectional area but 3 different sectional shapes (half-circle shape and U-type shapes) (Table 1). The three testing samples used in the study were saline, rabbit and human whole blood. Blood was collected from two rabbits (two male, Japanese albino, body weight 3.5–3.6 kg) and three healthy young adults (three male and one female, aged 21–22). Blood was drawn from the healthy young adults after they gave informed consent. Vacuum blood-collecting tubes containing anti-coagulant (EDTA-2K, Terumo Co., Japan) were used for collection of rabbit and human whole blood. First, the semi-invasive blood-collecting needles were installed onto a xyz stage. Immediately after 2 mL of the sample was dropped onto a polyester film, the needle was moved vertically to touch the sample, and the time and volume of capillary action were measured. The time for action was defined as a period from an instance when the needle touched the sample to the time when the half-open trough of the needle was filled with the sample. A high-accuracy CCD camera monitored the whole process, and the action time was calculated from the video monitor. The sample mass was calculated by measuring the weights of the needle before and after action using an electric balance (minimum display 10 mg, HM202, A&D Co., Ltd., Japan). Since, the physical properties of collected whole blood samples, particularly viscosity, altered with time, all the experiments were performed within 1 h after blood collection.
M. Yamaguchi et al. / Diabetes Research and Clinical Practice 66S (2004) S179–S183
S181
Fig. 1. External view of the semi-invasive blood-sampling needle (MI-1).
2.2. In vivo evaluation In order to evaluate the degree of invasiveness and irritation of the semi-invasive blood-collecting needles, the changes in diameter of the erythemas were
Table 1 Three types of the semi-invasive blood-sampling needle fabricated
compared with that produced by a 25G blood-collecting needle (unprocessed, commercially available, regular). A rabbit ear was pierced vertically with the testing semi-invasive blood-collecting needles to avoid arterial or venous vessels, and the changes in diameter of the erythema were examined for 2 days. Three semi-invasive and one regular 25 G blood-collecting needles were fixed with a constant distance (12.5 mm) between skin and needle. A rabbit ear was punctured six times with each needle, using two different animals. The diameter of the erythema was measured with a pair of calipers. For each needle, two independent testers measured the shortest and longest diameters of the six erythemas separately. The average of the all measured values for each needle was defined as a representative of the diameter of the erythema on that day.
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M. Yamaguchi et al. / Diabetes Research and Clinical Practice 66S (2004) S179–S183
3. Results 3.1. In vitro evaluation Saline and rabbit whole blood were compared for the relationship between section shape and size and the action time and volume (Table 2). When saline was used, it was found that the action time was reduced as the inner diameter became smaller, while there was no significant difference in the action volume. Since, the rabbit whole blood was more viscous than saline, the action time increased by 6- to 6.9-fold with 27–48% reduction in the action volume when using rabbit whole blood. However, our goal for a minimum volume of 0.1 mL was maintained. Next, using human whole blood, the relationship between the sectional shape and size and the action time and volume were evaluated (Fig. 2). The results were similar to those using the rabbit whole blood the action time was increased by 6.2- to 6.8-fold as compared to those of saline. However, the mean action time by MI-3, whose inner diameter was smaller, was 9.3 s, which was relatively short. The action volume was also reduced when compared to that from saline. When MI-3 was used, all three healthy human subjects achieved the minimum volume of 0.1 mL, and the mean value was 0.18 mL.
Fig. 2. Results of suction characteristics using whole human blood (n = 3).
3.2. In vivo evaluation When the erythema size was evaluated in vivo using a pair of calipers, the diameter of the erythema produced by a commercially available, regular needle was distributed between 0.3 and 2 mm (Fig. 3). When all semiinvasive blood-collecting needles were compared, there was no significant difference in the erythema sizes among three needles with three different shapes, all
0.17 mm
being less than 1 mm. The mean, maximum and minimum values of these three semi-invasive blood-collecting needles were 0.47, 0.71 and 0.14 mm, respectively. Moreover, there was no significant difference between 1 and 2 days after puncture for all needles.
1.5 0.4 0.22 0.05
4. Discussion
Table 2 Comparison of suction characteristics between isotonic sodium chloride solution and whole rabbit blood (mean SD) Type
MI-1
MI-2
Inner diameter 0.28 mm 0.22 mm Isotonic sodium chloride solution (n = 10) Suction time (s) 2.0 0.9 2.3 1.0 Suction volume (mL) 0.23 0.03 0.23 0.03 Whole rabbit blood (n = 5) Suction time (s) 13.7 5.3 Suction volume (mL) 0.12 0.07
– –
Fig. 3. The changes of the major diameter of erythema in the auricles rabbits.
MI-3
9.0 4.1 0.16 0.07
In the comparison of the needle shape and size using saline, we demonstrated that the smaller the
M. Yamaguchi et al. / Diabetes Research and Clinical Practice 66S (2004) S179–S183
inner diameter of the needle became, the more the capillary action force by capillary phenomenon was increased, resulting in a significant increase in capillary action velocity. However, there was no significant difference in action volume because the sectional area was set as a constant. Since, it was confirmed that capillary action could be positively utilized for the in vitro evaluation with saline, only MI-1 and MI-3 needles were used for evaluation using rabbit and human blood samples. When the physical properties of the semi-invasive blood-collecting needles were evaluated from the experiments using human whole blood samples, it was confirmed that more than 0.1 mL of blood sample could be collected easily within 10 s by selecting the needle sectional shape and size. As for in vivo evaluation, the diameter of the erythemas produced by the semi-invasive needles was less than half of that produced by a regular, commercially available needle with the same gauge. Thus, it was suggested that the degree of invasiveness might be smaller with these methods. The commercially available needle with the same sectional area as that of MI-3 are 28G. Therefore, it was indicated that use of the collecting needles with a half-circle or U-shape produced an effect to reduce the cross-sectional area of the needles.
5. Conclusion We have developed methods for blood collection using a semi-invasive needle that has a half-open
S183
trough at the pointed end and could automatically collect a small but sufficient volume of blood sample by capillary action alone. When the blood attracting time and volume were evaluated as its physical properties, it was confirmed that approximately 0.1 mL of human whole blood sample could be drawn within 10 s by selection of the needle’s shape and size. Moreover, observation of the temporal changes in the diameter of the erythemas revealed that the devised needles were less invasive as compared to a commercially available needle with the same gauge. These results clarified the basic capacity of the semi-invasive blood-collecting needles that we had fabricated in the current study.
References [1] D. Gan (Ed.). Diabetes Atlas 2000. Executive summary, International Diabetes Federation, Brussels, 2001. [2] J.C. Jones, The feeding behavior of mosquitoes, Sci. Am. 238 (1978) 113–120. [3] H. Komine, O. Takahashi, H. Saito, T. Togawa, Automatic blood sampler aimed at blood sucking mechanism of mosquito, Rep. Inst. Med. Dent. Eng. 27 (1993) 57–63 (in Japanese). [4] K. Kobayashi, H. Suzuki, A sampling mechanism employing the phase transition of a gel and its application to a micro analysis system imitating a mosquito, Sens. Actuators B 80 (2001) 1–8. [5] T. Shin-ei, K. Yuyama, M. Ujihira, K. Mabuchi, Reduction of insertion force of medical devices into biological tissues by vibration, Jpn. J. Med. Electron. Biol. Eng. 39 (2001) 292–296 (in Japanese).
Proposal of blood-collecting needle approach to semi-invasive method Masaki Yamaguchia,*, Yuji Kawabataa, Katsuya Yamazakib, Masashi Kobayashib, Takehito Itoc a
Department of Material Systems Engineering and Life Science, Faculty of Engineering, Toyama University, 3190 Gofuko, Toyama 930-8555, Japan b The First Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan c International Medical Division, Nipro Co., Osaka, Japan Received 14 July 2003; accepted 11 August 2003
Abstract Many diabetic patients carry a portable self-monitoring of blood glucose (SMBG)-analyzer in order to collect their own blood and examine their glucose levels; this allows them to determine such factors as insulin dose, diet and exercise to stay healthy. However, the test causes physical and mental stress for the subjects. The authors aim to develop a semi-invasive bloodcollecting needle which does not need a power source for the pump mechanism. In this study, we fabricated a capillary action needle that can collect the blood sample automatically. A blood-collecting needle was fabricated from 25 gage sized medical needle (diameter of 0.5 mm, stainless steel) by cutting process, and it had a half-opened crevice in the tip. In order to evaluate the physical characteristics of the blood-collecting needle, the relationship between the size and suction time and/or suction volume were measured using an isotonic sodium chloride solution, whole rabbit blood, and whole human blood with anticoagulant. Next, in order to evaluate the degree of invasion, the diameters of erythema in auricles of rabbits were observed for 2 days using a CCD camera-type microscope. The mean suction time of the isotonic sodium chloride solution and the whole rabbit blood were 1.5 s (n = 10) and 9.0 s (n = 5), respectively. Selection of a suitable size of the blood-collecting needle enabled the collection of 0.1 mL of whole human blood in 10 s. Moreover, it was shown, by comparing the observed diameter of the erythema, that the invasiveness of the blood-collecting needle was smaller than for commercial needles of the equal diameter. It became clear that this fulfils the fundamental functions of a semi-invasive blood-collecting needle. # 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Semi-invasive; Self-monitoring of blood glucose; Needle; Capillary action
1. Introduction * Corresponding author. Tel.: +81 76 445 6855; fax: +81 76 445 6855. E-mail address: [email protected] (M. Yamaguchi).
The total number of diabetic patients worldwide was estimated to be more than 150 million in
0168-8227/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2003.08.016
S180
M. Yamaguchi et al. / Diabetes Research and Clinical Practice 66S (2004) S179–S183
2000 [1]. Since, severe diabetic patients need a daily injection of insulin and daily blood collection for monitoring their blood glucose, better semi-invasive methods for blood collection urgently need to be developed. If the volume of collected blood could be reduced to approximately 0.1 mL, this could result in almost complete disappearance of the physical pain caused by needling. This would be good news for the diabetic patients who have to frequently collect their blood for monitoring blood glucose. However, as the inner width of collecting needles gets smaller, the viscous resistance increases due to increased friction caused by the inner wall of the needle and blood, resulting in difficulties in blood collection when a specific pumping device is not also used. Moreover, it is also known that too much negative pressure may modify the blood properties. Increased viscous resistance is a negative factor to the development of clinical blood glucose monitors, in a small, portable format. Thus, the development of blood collecting systems that mimic the blood-sucking device of the mosquito’s snout, which can penetrate human skins and suck up the blood, have long been investigated [2–5]. It is very important to develop a semi-invasive blood-collecting needle, which can automatically draw a small but sufficient amount of blood without requiring any pumping device, as they generally require a small power-source. We have developed a collecting needle, which automatically collects blood by capillary action. The fabricated needle had a halfopen trough formed at the pointed end. The driving force of the pump was caused by capillary action due to the intermolecular forces between the needle and the blood. In this study, we report the results regarding fabricated semi-invasive blood-collecting needles. In vitro physical properties of the semi-invasive bloodcollecting needles were evaluated using saline, rabbit and human whole blood. The physical properties investigated were the relationship between section shape and size of the needle, and the time and volume required for action. Then the in vivo properties were examined in order to evaluate the degree of invasiveness and irritation, by measuring the changes in diameter of the erythema made by puncturing rabbit ears.
2. Materials and methods 2.1. In vitro evaluation A semi-invasive blood-collecting needle was fabricated, which had a half-open trough at the pointed head of the needle. A stainless steel blood-collecting needle (SUS304) with gauge 25 (outer diameter 0.50 mm, the unit showing the width of the needle is defined as G below) was cut and processed with electrolytic grinding to create the semi-invasive blood-collecting needle (Fig. 1). In order to evaluate the relationship between the needle section shape and size and the time and volume required for action, 3 semi-invasive collecting needles (MI-1–MI-3) were fabricated that had the same cross-sectional area but 3 different sectional shapes (half-circle shape and U-type shapes) (Table 1). The three testing samples used in the study were saline, rabbit and human whole blood. Blood was collected from two rabbits (two male, Japanese albino, body weight 3.5–3.6 kg) and three healthy young adults (three male and one female, aged 21–22). Blood was drawn from the healthy young adults after they gave informed consent. Vacuum blood-collecting tubes containing anti-coagulant (EDTA-2K, Terumo Co., Japan) were used for collection of rabbit and human whole blood. First, the semi-invasive blood-collecting needles were installed onto a xyz stage. Immediately after 2 mL of the sample was dropped onto a polyester film, the needle was moved vertically to touch the sample, and the time and volume of capillary action were measured. The time for action was defined as a period from an instance when the needle touched the sample to the time when the half-open trough of the needle was filled with the sample. A high-accuracy CCD camera monitored the whole process, and the action time was calculated from the video monitor. The sample mass was calculated by measuring the weights of the needle before and after action using an electric balance (minimum display 10 mg, HM202, A&D Co., Ltd., Japan). Since, the physical properties of collected whole blood samples, particularly viscosity, altered with time, all the experiments were performed within 1 h after blood collection.
M. Yamaguchi et al. / Diabetes Research and Clinical Practice 66S (2004) S179–S183
S181
Fig. 1. External view of the semi-invasive blood-sampling needle (MI-1).
2.2. In vivo evaluation In order to evaluate the degree of invasiveness and irritation of the semi-invasive blood-collecting needles, the changes in diameter of the erythemas were
Table 1 Three types of the semi-invasive blood-sampling needle fabricated
compared with that produced by a 25G blood-collecting needle (unprocessed, commercially available, regular). A rabbit ear was pierced vertically with the testing semi-invasive blood-collecting needles to avoid arterial or venous vessels, and the changes in diameter of the erythema were examined for 2 days. Three semi-invasive and one regular 25 G blood-collecting needles were fixed with a constant distance (12.5 mm) between skin and needle. A rabbit ear was punctured six times with each needle, using two different animals. The diameter of the erythema was measured with a pair of calipers. For each needle, two independent testers measured the shortest and longest diameters of the six erythemas separately. The average of the all measured values for each needle was defined as a representative of the diameter of the erythema on that day.
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M. Yamaguchi et al. / Diabetes Research and Clinical Practice 66S (2004) S179–S183
3. Results 3.1. In vitro evaluation Saline and rabbit whole blood were compared for the relationship between section shape and size and the action time and volume (Table 2). When saline was used, it was found that the action time was reduced as the inner diameter became smaller, while there was no significant difference in the action volume. Since, the rabbit whole blood was more viscous than saline, the action time increased by 6- to 6.9-fold with 27–48% reduction in the action volume when using rabbit whole blood. However, our goal for a minimum volume of 0.1 mL was maintained. Next, using human whole blood, the relationship between the sectional shape and size and the action time and volume were evaluated (Fig. 2). The results were similar to those using the rabbit whole blood the action time was increased by 6.2- to 6.8-fold as compared to those of saline. However, the mean action time by MI-3, whose inner diameter was smaller, was 9.3 s, which was relatively short. The action volume was also reduced when compared to that from saline. When MI-3 was used, all three healthy human subjects achieved the minimum volume of 0.1 mL, and the mean value was 0.18 mL.
Fig. 2. Results of suction characteristics using whole human blood (n = 3).
3.2. In vivo evaluation When the erythema size was evaluated in vivo using a pair of calipers, the diameter of the erythema produced by a commercially available, regular needle was distributed between 0.3 and 2 mm (Fig. 3). When all semiinvasive blood-collecting needles were compared, there was no significant difference in the erythema sizes among three needles with three different shapes, all
0.17 mm
being less than 1 mm. The mean, maximum and minimum values of these three semi-invasive blood-collecting needles were 0.47, 0.71 and 0.14 mm, respectively. Moreover, there was no significant difference between 1 and 2 days after puncture for all needles.
1.5 0.4 0.22 0.05
4. Discussion
Table 2 Comparison of suction characteristics between isotonic sodium chloride solution and whole rabbit blood (mean SD) Type
MI-1
MI-2
Inner diameter 0.28 mm 0.22 mm Isotonic sodium chloride solution (n = 10) Suction time (s) 2.0 0.9 2.3 1.0 Suction volume (mL) 0.23 0.03 0.23 0.03 Whole rabbit blood (n = 5) Suction time (s) 13.7 5.3 Suction volume (mL) 0.12 0.07
– –
Fig. 3. The changes of the major diameter of erythema in the auricles rabbits.
MI-3
9.0 4.1 0.16 0.07
In the comparison of the needle shape and size using saline, we demonstrated that the smaller the
M. Yamaguchi et al. / Diabetes Research and Clinical Practice 66S (2004) S179–S183
inner diameter of the needle became, the more the capillary action force by capillary phenomenon was increased, resulting in a significant increase in capillary action velocity. However, there was no significant difference in action volume because the sectional area was set as a constant. Since, it was confirmed that capillary action could be positively utilized for the in vitro evaluation with saline, only MI-1 and MI-3 needles were used for evaluation using rabbit and human blood samples. When the physical properties of the semi-invasive blood-collecting needles were evaluated from the experiments using human whole blood samples, it was confirmed that more than 0.1 mL of blood sample could be collected easily within 10 s by selecting the needle sectional shape and size. As for in vivo evaluation, the diameter of the erythemas produced by the semi-invasive needles was less than half of that produced by a regular, commercially available needle with the same gauge. Thus, it was suggested that the degree of invasiveness might be smaller with these methods. The commercially available needle with the same sectional area as that of MI-3 are 28G. Therefore, it was indicated that use of the collecting needles with a half-circle or U-shape produced an effect to reduce the cross-sectional area of the needles.
5. Conclusion We have developed methods for blood collection using a semi-invasive needle that has a half-open
S183
trough at the pointed end and could automatically collect a small but sufficient volume of blood sample by capillary action alone. When the blood attracting time and volume were evaluated as its physical properties, it was confirmed that approximately 0.1 mL of human whole blood sample could be drawn within 10 s by selection of the needle’s shape and size. Moreover, observation of the temporal changes in the diameter of the erythemas revealed that the devised needles were less invasive as compared to a commercially available needle with the same gauge. These results clarified the basic capacity of the semi-invasive blood-collecting needles that we had fabricated in the current study.
References [1] D. Gan (Ed.). Diabetes Atlas 2000. Executive summary, International Diabetes Federation, Brussels, 2001. [2] J.C. Jones, The feeding behavior of mosquitoes, Sci. Am. 238 (1978) 113–120. [3] H. Komine, O. Takahashi, H. Saito, T. Togawa, Automatic blood sampler aimed at blood sucking mechanism of mosquito, Rep. Inst. Med. Dent. Eng. 27 (1993) 57–63 (in Japanese). [4] K. Kobayashi, H. Suzuki, A sampling mechanism employing the phase transition of a gel and its application to a micro analysis system imitating a mosquito, Sens. Actuators B 80 (2001) 1–8. [5] T. Shin-ei, K. Yuyama, M. Ujihira, K. Mabuchi, Reduction of insertion force of medical devices into biological tissues by vibration, Jpn. J. Med. Electron. Biol. Eng. 39 (2001) 292–296 (in Japanese).