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Design and fabrication of an electrostatically driven microgripper for blood vessel manipulation
Microelectronic Engineering 83 (2006) 1651–1654 www.elsevier.com/locate/mee
Design and fabrication of an electrostatically driven microgripper for blood vessel manipulation R. Wierzbicki a,*, K. Houston b, H. Heerlein a, W. Barth a, T. Debski a, A. Eisinberg b, A. Menciassi b, M.C. Carrozza b, P. Dario b b
a Nascatec GmbH, Kassel 34131, Germany CRIM Lab, Scuole Superiore Sant’Anna, Pisa 56025, Italy
Available online 17 February 2006
Abstract This work is focused on the design and the fabrication of an electrostatically driven microgripper for blood vessel manipulation. The goal is to realise a new system for the automated study of blood vessel wall contraction forces. Our device is based on an electrostatic comb-drive actuated silicon microgripper whose tips can be inserted into blood vessel samples providing isostatic conditions during the test and allowing contraction force measurement in the range of a few mN. A major innovation of the tool compared with existing devices is the capability of scaling down the diameter of the vessels that can be tested, reaching an internal diameter of 50 lm. In the paper a brief overview of the state of the art is presented, design details, simulations results and steps of the fabrication process are described. 2006 Elsevier B.V. All rights reserved. Keywords: Micromanipulation; Bio-MEMS; Microgripper; Comb drive actuators
1. Introduction One of the main research lines active in the field of physiology nowadays consists of the study of mechanisms which regulate the blood flow through the different organs of the human body. This control is mainly located in the small arteries which precede the network of capillaries and which, with suitable dimensional adjustment, present different resistances to the blood flow (‘‘resistance’’ blood vessels). Even though this is well known, most of the recent studies have been performed by using, for methodological reasons, bigger blood vessels (‘‘conduction’’ blood vessels), with results which are not relevant or even incorrect. One of the most challenging research activity is related to the study of pulmonary circulation, which undergoes major changes during the transition from the fetal to the *
Corresponding author. Tel.: +49 0 561 920 88 300; fax: +49 0 561 920 88 309. E-mail address: [email protected] (R. Wierzbicki). 0167-9317/$ - see front matter 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.mee.2006.01.110
neonatal state, resulting in a fall in vascular resistance. Through the years, the mechanisms responsible for the elevated resistance in the fetus and the dilatation of blood vessels at birth have been intensively investigated, and several vasoactive agents have been used in both processes. Since there are important repercussions in clinical practice as regards new-born children that experience difficulty in breathing at birth, nowadays it is very important to acquire new knowledge and to find well assessed methodologies for performing experimental tests. The goal of this work is to design and fabricate a tool which can measure the contraction forces in blood vessels, and to be able to manipulate vessels which are much smaller than those currently used in the state of the art. 2. State of the art The current set-up allows measuring of the force generated in blood vessels with diameter of about 150 lm and length of about 500 lm [1]. The experimental procedure is
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R. Wierzbicki et al. / Microelectronic Engineering 83 (2006) 1651–1654
as follows: the microvessel is manually isolated by dissection in a physiological solution bath with a suitable oxygen concentration and then fixed (by inserting two 25 lm diameter tungsten wires into the microvessel) to a dedicated support. Afterwards, the preparation is moved to a second workbench and immersed in a physiological bath. A skilled operator performs all the procedure under microscope and this is a demanding task in terms of manual skill. The second workbench is equipped with two micromanipulators, a force transducer mechanically interfaced to one of the wires, and a microscope and temperature sensor for the bath. In the last few years, further research efforts have been devoted [2] to the development of several alternative procedures, in order to decrease the stress on the operator and to enhance the reliability of the overall task. Different miniaturized devices have been tested in bigger vessels (mainly a mouse aorta, with a diameter of 700 lm), as illustrated in Figs. 1 and 2 and represented a good starting point for the design of the proposed solution in the present work
3. Proposed system concept This work is focused on the design and fabrication of an electrostatically driven microgripper as an effective solution to face the current difficulties in procedures of manual vessel micromanipulation in terms of accuracy, reliability and stress for the operator. The goal is to realise a new system for the automated study of blood vessel wall contraction forces, and two issues in the current system are critical: ease of handling of the vessel, and the vessel wall contraction force measurement under isostatic conditions. The proposed solution is the introduction of a purposely developed silicon-based sensor. With the proposed silicon-based sensor, the minimum diameter of the microvessels could be as small as 50 lm, thus investigating the mechanical behaviour of resistance blood vessels would be feasible. The use of silicon may also allow the future integration into the same device of a chemically reactive coat for measuring concomitantly biologically active substances such as nitric oxide and carbon monoxide (dual mechanical/chemical sensor). 4. Design of the microgripper
Blood vessel Tungsten Wire
Force sensor
4.1. Technical specification To meet the requirements of proper vessel contraction force measurement, the gripper must perform the following: parallel movement of tweezers, actuation force in a range of 5 mN and structure stiffness high enough to provide isostatic conditions during measurement. Gripper arms with tips must be located outside the structure to maintain ease manipulation and immersion in the physiological liquid. 4.2. Device structure
Fig. 1. Strain gauge sensor in the microvessel, diameter 700 lm.
The general structure sketch is shown in Fig. 3. Moveable part of the device is suspended on series of flat spring systems (A and B – Fig. 3), which also play a role of a retracting and counter force (to the electrostatic force generated by combs) system. 4.3. Comb-driven actuation
Blood vessel
Tungsten wire
Fig. 2. Strain gauge with an integrated thin glass fiber, inserted into the blood vessel.
Actuation part of the structure consists of two independent electrostatic comb actuators, each of them capable to generate electrostatic force of 5 mN at maximum value of driving voltage 185 V. Implementation of two actuators is needed to compensate a tilting of the structure caused by out-of-symmetry placement of the tips and thus the vessel contraction force point of application. The force generated by combs can be estimated by the following equation [5]: t F el ðU Þ ¼ N e U 2 ð1Þ g where N = 500-number of comb pairs, e = 8.85 · 1012 F/ m – permittivity, t = 50 lm – device layer thickness, g = 3 lm – finger gap.
R. Wierzbicki et al. / Microelectronic Engineering 83 (2006) 1651–1654 Table 1 Results obtained within the FEM simulation P P Fa Fb Dxmax 0.5 FV (mN) (mN) (mN) (lm)
L9
L4
L2
0.5FV L7
L8
Σ FB
B
L6
A
Σ FA
Dy1max (lm)
Dy2max (lm)
0 2.5 2.5 0.17 22.2 22.2 2.5 0.5 2.5 0.39 1.57 0.07 2.5 0 0 0.30 2.22 7.97 P P Fa – force generated by actuator 1, Fb – force generated by actuator 2, Dxmax – maximum displacement of comb structure in the direction parallel to comb axis, Dy1max, Dy2max – displacements of actuators 1 and 2 (respectively) in the actuating direction.
L1
L5
1653
B
A L3
Fig. 3. Schematic drawing of designed structure. Critical dimensions: L1 = 3700 lm; L2 = 782 lm; L3 = 1276 lm; L4 = 10 lm; L5 = 150 lm; L6 = 120 lm; L7 = 155 lm; L8 = 118 lm; L9 = 150 lm. Spring systems (A and B): length: LS = 275 lm, width: wS = 6 lm.
Results show that full range of the tip movement is 22.2 lm with the applied voltage of 185 V at both actuators. In a second case, when force of 2.5 mN is applied at the tip of the gripper (maximum of the predicted vessel contraction force), the equilibrium, and thus isostatic condition is achieved with first actuator generating force at level slightly below 500 lm (U = 80 V) and second actuator generating force at level of 2.5 mN (U = 185 V). During actuation, maximum displacement of the actuator in the parallel direction to the actuation direction does not exceed the level of 400 nm, which result assures, that no risk of structure buckling and wedging of combs exist. 4.5. Displacement sensing comb structures
g
ov LF
w Fig. 4. Comb actuator geometry: finger width: w = 3 lm, length LF = 30 lm and overlap oV = 5 lm.
4.4. Structural mechanics FEM simulation To obtain information about gripper structural stiffness and its behaviour during actuation, mechanics of the whole structure has been simulated with an FEM method. Parameters of simulation were set as follows: meshing: 2D, 4node structural solid elements; plane stress model (thickness value set to 50 lm); quadrangular elements with maximum size 2.5 lm; material density: q = 2329 kg/m3, linear elastic anisotropic model of material (single crystal silicon): d11 = d22 = d33 = 167.4 GPa; d12 = d13 = d23 = 65.2 GPa; d44 = d55 = d66 = 79.6 GPa; rest of coefficients equal to zero [6]. Three loading cases were simulated. Loading values and obtained results are shown in Table 1.
A device capable to work in the close loop control, must have integrated a force/displacement sensing element. Comb structures (Fig. 4), apart from actuation mode, can be utilized as a position sensing ones. While high voltage applied in a quasi-static mode is utilized as a signal for actuation, high frequency, low amplitude signal applied to the structure will be used to determine actual capacitance and thus position of the device’s moving part [5]. Capacitance of the comb structure, as a parallel plate capacitor, can be evaluated from: CðDxÞ ¼ 2N e
ðDx þ oV Þt g
ð2Þ
where Dx is a detected displacement and oV is initial overlapping. In the case of the designed device, for each of four actuators (two per one gripper arm), capacitance varies in a range 1.5–4.4 pF for a travel of 20 lm, with a sensitivity of 1.5 pF/lm. 5. Fabrication sequence The gripper is fabricated by use of single crystal silicon micromachining technology. The process proceeds as follows. SOI wafer is structured from the backside with KOH wet anisotropic etching and gripper holder is created. Then, on the top of wafer hard mask of SiO2 is patterned. The following gas chopping DRIE process creates the gripper structure [3,4]. Further on the buried oxide (BOX) layer is etched in HF solution. At a properly defined structure, some parts of it must remain connected after BOX layer
1654
R. Wierzbicki et al. / Microelectronic Engineering 83 (2006) 1651–1654
(a)
MASK
(b)
MASK
SOI
SOI
trol. The mechanical and electrical subsystems will be tested and calibrated, and then the microgripper will be implemented in tests to measure the contraction force in mouse aorta vessels. Acknowledgement
(c)
MASK
SOI
Fig. 5. Fabrication process sequence: (a) KOH etching of the backside; (b) dry etching of the device layer; (c) underetching of the buried SiO2 (BOX) layer.
This work was supported by ‘ASSEMIC’ EU training network Project No. 504826. The work described in this paper has been in part supported by the Commission of the European Community: European FET – Open Project IST 2001-33567 ‘‘MiCRoN – Micro-robots advancing towards the nano range’’. The authors thank Mr. C. Filippeschi for his technical contribution. Moreover, they are grateful to Prof. Coceani and Dr. Baragatti for their collaboration. References
etching, and some must become free. This is done by a controlled etching of the buried oxide layer. Structure features with width lower than certain critical value are fully underetched and become free-hanging, while those broad enough remain connected through oxide to the holder [3,4] (Fig. 5). 6. Conclusions and future work An electrostatically driven microgripper with a tilt compensation mechanism has been designed for measurement of the contraction force of blood vessels of diameter as small as 50 lm. The microgripper structure has been analysed using FEA simulation method. Future work includes fabrication and testing of the prototypes and the design of a closed loop control system for displacement/force con-
[1] Y. Wang, F. Coceani, Isolated pulmonary resistance vessels from fetal lambs. Contractile behaviour and responses to indomethacin and endothelin-1, Circ. Res. 71 (1992) 320–330. [2] T. Chataigneau, M. Fe´le´tou, P.L. Huang, M.C. Fishman, J. Duhault, P.M. Vanhoutte, Acetylcholine-induced relaxation in blood vessels from endothelial nitric oxide synthase knockout mice, Br. J. Pharmacol. 126 (1999) 219–226. [3] B.E. Volland, H. Heerlein, I.W. Rangelow, Electrostatically driven microgripper, Microelectron. Eng. 61–62 (2002) 1015–1023. [4] B.E Volland, H. Heerlein, I. Kostic, I.W. Rangelow, The application of secondary effects in high aspect ratio dry etching for the fabrication of MEMS, Microelectron. Eng. 57–58 (2001) 641–650. [5] Ch. Liu, Y. Bar-Cohen, Scaling laws of microactuators and potential applications of electroactive polymers in MEMS’’, in: Proceedings of SPIE’s 6th Annual International Symposium on Smart Structures and Materials, 1–5 March, 1999, Newport Beach, CA (Paper No. 3669-33). [6] ANSYS 5.2 Manual.
Design and fabrication of an electrostatically driven microgripper for blood vessel manipulation R. Wierzbicki a,*, K. Houston b, H. Heerlein a, W. Barth a, T. Debski a, A. Eisinberg b, A. Menciassi b, M.C. Carrozza b, P. Dario b b
a Nascatec GmbH, Kassel 34131, Germany CRIM Lab, Scuole Superiore Sant’Anna, Pisa 56025, Italy
Available online 17 February 2006
Abstract This work is focused on the design and the fabrication of an electrostatically driven microgripper for blood vessel manipulation. The goal is to realise a new system for the automated study of blood vessel wall contraction forces. Our device is based on an electrostatic comb-drive actuated silicon microgripper whose tips can be inserted into blood vessel samples providing isostatic conditions during the test and allowing contraction force measurement in the range of a few mN. A major innovation of the tool compared with existing devices is the capability of scaling down the diameter of the vessels that can be tested, reaching an internal diameter of 50 lm. In the paper a brief overview of the state of the art is presented, design details, simulations results and steps of the fabrication process are described. 2006 Elsevier B.V. All rights reserved. Keywords: Micromanipulation; Bio-MEMS; Microgripper; Comb drive actuators
1. Introduction One of the main research lines active in the field of physiology nowadays consists of the study of mechanisms which regulate the blood flow through the different organs of the human body. This control is mainly located in the small arteries which precede the network of capillaries and which, with suitable dimensional adjustment, present different resistances to the blood flow (‘‘resistance’’ blood vessels). Even though this is well known, most of the recent studies have been performed by using, for methodological reasons, bigger blood vessels (‘‘conduction’’ blood vessels), with results which are not relevant or even incorrect. One of the most challenging research activity is related to the study of pulmonary circulation, which undergoes major changes during the transition from the fetal to the *
Corresponding author. Tel.: +49 0 561 920 88 300; fax: +49 0 561 920 88 309. E-mail address: [email protected] (R. Wierzbicki). 0167-9317/$ - see front matter 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.mee.2006.01.110
neonatal state, resulting in a fall in vascular resistance. Through the years, the mechanisms responsible for the elevated resistance in the fetus and the dilatation of blood vessels at birth have been intensively investigated, and several vasoactive agents have been used in both processes. Since there are important repercussions in clinical practice as regards new-born children that experience difficulty in breathing at birth, nowadays it is very important to acquire new knowledge and to find well assessed methodologies for performing experimental tests. The goal of this work is to design and fabricate a tool which can measure the contraction forces in blood vessels, and to be able to manipulate vessels which are much smaller than those currently used in the state of the art. 2. State of the art The current set-up allows measuring of the force generated in blood vessels with diameter of about 150 lm and length of about 500 lm [1]. The experimental procedure is
1652
R. Wierzbicki et al. / Microelectronic Engineering 83 (2006) 1651–1654
as follows: the microvessel is manually isolated by dissection in a physiological solution bath with a suitable oxygen concentration and then fixed (by inserting two 25 lm diameter tungsten wires into the microvessel) to a dedicated support. Afterwards, the preparation is moved to a second workbench and immersed in a physiological bath. A skilled operator performs all the procedure under microscope and this is a demanding task in terms of manual skill. The second workbench is equipped with two micromanipulators, a force transducer mechanically interfaced to one of the wires, and a microscope and temperature sensor for the bath. In the last few years, further research efforts have been devoted [2] to the development of several alternative procedures, in order to decrease the stress on the operator and to enhance the reliability of the overall task. Different miniaturized devices have been tested in bigger vessels (mainly a mouse aorta, with a diameter of 700 lm), as illustrated in Figs. 1 and 2 and represented a good starting point for the design of the proposed solution in the present work
3. Proposed system concept This work is focused on the design and fabrication of an electrostatically driven microgripper as an effective solution to face the current difficulties in procedures of manual vessel micromanipulation in terms of accuracy, reliability and stress for the operator. The goal is to realise a new system for the automated study of blood vessel wall contraction forces, and two issues in the current system are critical: ease of handling of the vessel, and the vessel wall contraction force measurement under isostatic conditions. The proposed solution is the introduction of a purposely developed silicon-based sensor. With the proposed silicon-based sensor, the minimum diameter of the microvessels could be as small as 50 lm, thus investigating the mechanical behaviour of resistance blood vessels would be feasible. The use of silicon may also allow the future integration into the same device of a chemically reactive coat for measuring concomitantly biologically active substances such as nitric oxide and carbon monoxide (dual mechanical/chemical sensor). 4. Design of the microgripper
Blood vessel Tungsten Wire
Force sensor
4.1. Technical specification To meet the requirements of proper vessel contraction force measurement, the gripper must perform the following: parallel movement of tweezers, actuation force in a range of 5 mN and structure stiffness high enough to provide isostatic conditions during measurement. Gripper arms with tips must be located outside the structure to maintain ease manipulation and immersion in the physiological liquid. 4.2. Device structure
Fig. 1. Strain gauge sensor in the microvessel, diameter 700 lm.
The general structure sketch is shown in Fig. 3. Moveable part of the device is suspended on series of flat spring systems (A and B – Fig. 3), which also play a role of a retracting and counter force (to the electrostatic force generated by combs) system. 4.3. Comb-driven actuation
Blood vessel
Tungsten wire
Fig. 2. Strain gauge with an integrated thin glass fiber, inserted into the blood vessel.
Actuation part of the structure consists of two independent electrostatic comb actuators, each of them capable to generate electrostatic force of 5 mN at maximum value of driving voltage 185 V. Implementation of two actuators is needed to compensate a tilting of the structure caused by out-of-symmetry placement of the tips and thus the vessel contraction force point of application. The force generated by combs can be estimated by the following equation [5]: t F el ðU Þ ¼ N e U 2 ð1Þ g where N = 500-number of comb pairs, e = 8.85 · 1012 F/ m – permittivity, t = 50 lm – device layer thickness, g = 3 lm – finger gap.
R. Wierzbicki et al. / Microelectronic Engineering 83 (2006) 1651–1654 Table 1 Results obtained within the FEM simulation P P Fa Fb Dxmax 0.5 FV (mN) (mN) (mN) (lm)
L9
L4
L2
0.5FV L7
L8
Σ FB
B
L6
A
Σ FA
Dy1max (lm)
Dy2max (lm)
0 2.5 2.5 0.17 22.2 22.2 2.5 0.5 2.5 0.39 1.57 0.07 2.5 0 0 0.30 2.22 7.97 P P Fa – force generated by actuator 1, Fb – force generated by actuator 2, Dxmax – maximum displacement of comb structure in the direction parallel to comb axis, Dy1max, Dy2max – displacements of actuators 1 and 2 (respectively) in the actuating direction.
L1
L5
1653
B
A L3
Fig. 3. Schematic drawing of designed structure. Critical dimensions: L1 = 3700 lm; L2 = 782 lm; L3 = 1276 lm; L4 = 10 lm; L5 = 150 lm; L6 = 120 lm; L7 = 155 lm; L8 = 118 lm; L9 = 150 lm. Spring systems (A and B): length: LS = 275 lm, width: wS = 6 lm.
Results show that full range of the tip movement is 22.2 lm with the applied voltage of 185 V at both actuators. In a second case, when force of 2.5 mN is applied at the tip of the gripper (maximum of the predicted vessel contraction force), the equilibrium, and thus isostatic condition is achieved with first actuator generating force at level slightly below 500 lm (U = 80 V) and second actuator generating force at level of 2.5 mN (U = 185 V). During actuation, maximum displacement of the actuator in the parallel direction to the actuation direction does not exceed the level of 400 nm, which result assures, that no risk of structure buckling and wedging of combs exist. 4.5. Displacement sensing comb structures
g
ov LF
w Fig. 4. Comb actuator geometry: finger width: w = 3 lm, length LF = 30 lm and overlap oV = 5 lm.
4.4. Structural mechanics FEM simulation To obtain information about gripper structural stiffness and its behaviour during actuation, mechanics of the whole structure has been simulated with an FEM method. Parameters of simulation were set as follows: meshing: 2D, 4node structural solid elements; plane stress model (thickness value set to 50 lm); quadrangular elements with maximum size 2.5 lm; material density: q = 2329 kg/m3, linear elastic anisotropic model of material (single crystal silicon): d11 = d22 = d33 = 167.4 GPa; d12 = d13 = d23 = 65.2 GPa; d44 = d55 = d66 = 79.6 GPa; rest of coefficients equal to zero [6]. Three loading cases were simulated. Loading values and obtained results are shown in Table 1.
A device capable to work in the close loop control, must have integrated a force/displacement sensing element. Comb structures (Fig. 4), apart from actuation mode, can be utilized as a position sensing ones. While high voltage applied in a quasi-static mode is utilized as a signal for actuation, high frequency, low amplitude signal applied to the structure will be used to determine actual capacitance and thus position of the device’s moving part [5]. Capacitance of the comb structure, as a parallel plate capacitor, can be evaluated from: CðDxÞ ¼ 2N e
ðDx þ oV Þt g
ð2Þ
where Dx is a detected displacement and oV is initial overlapping. In the case of the designed device, for each of four actuators (two per one gripper arm), capacitance varies in a range 1.5–4.4 pF for a travel of 20 lm, with a sensitivity of 1.5 pF/lm. 5. Fabrication sequence The gripper is fabricated by use of single crystal silicon micromachining technology. The process proceeds as follows. SOI wafer is structured from the backside with KOH wet anisotropic etching and gripper holder is created. Then, on the top of wafer hard mask of SiO2 is patterned. The following gas chopping DRIE process creates the gripper structure [3,4]. Further on the buried oxide (BOX) layer is etched in HF solution. At a properly defined structure, some parts of it must remain connected after BOX layer
1654
R. Wierzbicki et al. / Microelectronic Engineering 83 (2006) 1651–1654
(a)
MASK
(b)
MASK
SOI
SOI
trol. The mechanical and electrical subsystems will be tested and calibrated, and then the microgripper will be implemented in tests to measure the contraction force in mouse aorta vessels. Acknowledgement
(c)
MASK
SOI
Fig. 5. Fabrication process sequence: (a) KOH etching of the backside; (b) dry etching of the device layer; (c) underetching of the buried SiO2 (BOX) layer.
This work was supported by ‘ASSEMIC’ EU training network Project No. 504826. The work described in this paper has been in part supported by the Commission of the European Community: European FET – Open Project IST 2001-33567 ‘‘MiCRoN – Micro-robots advancing towards the nano range’’. The authors thank Mr. C. Filippeschi for his technical contribution. Moreover, they are grateful to Prof. Coceani and Dr. Baragatti for their collaboration. References
etching, and some must become free. This is done by a controlled etching of the buried oxide layer. Structure features with width lower than certain critical value are fully underetched and become free-hanging, while those broad enough remain connected through oxide to the holder [3,4] (Fig. 5). 6. Conclusions and future work An electrostatically driven microgripper with a tilt compensation mechanism has been designed for measurement of the contraction force of blood vessels of diameter as small as 50 lm. The microgripper structure has been analysed using FEA simulation method. Future work includes fabrication and testing of the prototypes and the design of a closed loop control system for displacement/force con-
[1] Y. Wang, F. Coceani, Isolated pulmonary resistance vessels from fetal lambs. Contractile behaviour and responses to indomethacin and endothelin-1, Circ. Res. 71 (1992) 320–330. [2] T. Chataigneau, M. Fe´le´tou, P.L. Huang, M.C. Fishman, J. Duhault, P.M. Vanhoutte, Acetylcholine-induced relaxation in blood vessels from endothelial nitric oxide synthase knockout mice, Br. J. Pharmacol. 126 (1999) 219–226. [3] B.E. Volland, H. Heerlein, I.W. Rangelow, Electrostatically driven microgripper, Microelectron. Eng. 61–62 (2002) 1015–1023. [4] B.E Volland, H. Heerlein, I. Kostic, I.W. Rangelow, The application of secondary effects in high aspect ratio dry etching for the fabrication of MEMS, Microelectron. Eng. 57–58 (2001) 641–650. [5] Ch. Liu, Y. Bar-Cohen, Scaling laws of microactuators and potential applications of electroactive polymers in MEMS’’, in: Proceedings of SPIE’s 6th Annual International Symposium on Smart Structures and Materials, 1–5 March, 1999, Newport Beach, CA (Paper No. 3669-33). [6] ANSYS 5.2 Manual.