Soft Spiral‐Shaped Microswimmers for Autonomous Swimming Control by Detecting Surrounding Environments

In nature, most microorganisms have motility, which is essential for their survival or reproduction. To move, some microorganisms have evolved soft spiral‐shaped flagella, which rotate through specialized motors. Many of these microorganisms can change the morphology of their spiral‐shaped flagella to control their motility. Herein, by mimicking these flagella, spiral‐shaped microswimmers are developed for various applications, such as target drug delivery, micro‐object transport, and micro‐fluid manipulation. In previous studies, numerous fabrication methods of spiral‐shaped microswimmers are developed. However, the swimming direction and velocity are controlled only by external systems, such as magnetic fields, because the spiral body is not able to deform. Therefore, this soft spiral‐shaped microswimmer for autonomous swimming control by detecting surrounding stimuli is proposed. The velocity of microswimmer largely depends on the geometry of the microswimmer's body. Through usage of a stimuli‐responsive hydrogel in the microswimmer, the geometry autonomously changes in response to the surrounding stimuli. Using finite‐element simulation, it is revealed that the pattern angle is an important parameter for acceleration/deceleration of the microswimmer. The dimensionless velocity of the fabricated bilayered spiral swimmer changes by deforming the geometry in response to the surrounding thermal stimuli.

DOI: 10.1002/aisy.202000095 In nature, most microorganisms have motility, which is essential for their survival or reproduction. To move, some microorganisms have evolved soft spiral-shaped flagella, which rotate through specialized motors. Many of these microorganisms can change the morphology of their spiral-shaped flagella to control their motility. Herein, by mimicking these flagella, spiral-shaped microswimmers are developed for various applications, such as target drug delivery, micro-object transport, and micro-fluid manipulation. In previous studies, numerous fabrication methods of spiral-shaped microswimmers are developed. However, the swimming direction and velocity are controlled only by external systems, such as magnetic fields, because the spiral body is not able to deform. Therefore, this soft spiral-shaped microswimmer for autonomous swimming control by detecting surrounding stimuli is proposed. The velocity of microswimmer largely depends on the geometry of the microswimmer's body. Through usage of a stimuli-responsive hydrogel in the microswimmer, the geometry autonomously changes in response to the surrounding stimuli. Using finite-element simulation, it is revealed that the pattern angle is an important parameter for acceleration/deceleration of the microswimmer. The dimensionless velocity of the fabricated bilayered spiral swimmer changes by deforming the geometry in response to the surrounding thermal stimuli.
our microswimmers are hydrogel and magnetic nanoparticles. The spiral-shaped microswimmer propels itself by rotational motion excited by magnetic fields. By patterning the stimuliresponsive hydrogel, the spiral shape changes in response to the environmental stimuli [22] and, therefore, the swimming motility of the microswimmer as well. In this study, we analyzed the propulsion velocity dependence on the geometry of the swimmer's body both theoretically and experimentally. Then, we demonstrated the change in propulsion velocity responding to the surrounding environment.
First, to design the microswimmer, the effects of geometric parameters on the propulsion velocity were theoretically evaluated. Microorganisms using spiral-shaped flagella for propulsion were modeled using resistive force theory at low Reynold's numbers. [6,23] Resistive force theory assigns a local drag coefficient to a cylindrical element of spiral-shaped flagella Figure 1. Soft spiral-shaped hydrogel microswimmers with autonomous swimming control. a) Swimming motility changed in response to the surrounding environments though a change in its geometry. b) The propulsion force was controlled by the geometry change. c) Parameters for the resistive force theory. d) Fabricated soft spiral-shaped microswimmers with different pitch angles. e) Schematic image of swimming conditions. f ) The swimming behaviors of spiral swimmers. g) The relationship between the dimensionless velocity, u*, and the pitch angle, α.
www.advancedsciencenews.com www.advintellsyst.com ( Figure 1c). For steady-state motion, the externally applied force, F, and torque, T, must equal the drag on the spiral-shaped microswimmer. In a simplified 1D model, the helical motion is described only by the rotation and translation along the spiral axis where u is the velocity, and ω is the rotation speed. The coefficients, a, b, and c, are the functions of geometric parameters and fluid viscosity. They can be modeled with the resistive force theory, resulting in where ξ ll and ξ n are drag coefficients along and perpendicular to the cylindrical axis, respectively. These drag coefficients for an infinitesimal cylindrical element on spiral-shaped flagella are defined by Lighthill [6] as where η is the fluid viscosity, and I is a spring index; I ¼ D spiral /D gel . When applying only a rotational magnetic field, the external force, F, is zero. Thus, the propulsion speed is calculated as According to Equation (2) and (3), the velocity, u, is described as ðξ ll À ξ n Þ cos α πnD spiral ð ξ ll cos 2 αþξ n sin 2 α sin α Þ ω Equation (7) can be rewritten by nondimensionalization to ignore the influence of the spiral diameter, D spiral , and the rotation speed, ω When the spring index, I, ranges from 2.8 to 5.0, the dimensionless velocity, u*, increases when the pitch angle, α, changes from 0 to %40 ( Figure S1a, Supporting Information). Thereafter, the dimensionless velocity, u*, decreases until the pitch angle, α, reaches %80 . Notably, the spring index, I, has little influence on the dimensionless velocity, u* (u* ¼ 0.098-0.118 during I ¼ 2.8-5.0 and α ¼ 40 ; Figure S1b, Supporting Information). Thus, we focused on only the pitch angle, α, which represents the degree of expansion and contraction of the spiral-shaped microswimmer for controlling the dimensionless velocity, u*.
For propulsion velocity observation, the fabricated spiral swimmers were placed into a chamber surrounded with orthogonal Helmholtz coils (Figure 1e). The chamber was filled with highly viscous fluid (1 M CaCl 2 þ 0.75 g mL À1 sucrose solution and viscosity η ¼ 12.6 mPa s). A rotational magnetic field (10 mT and 5 Hz) was applied to the spiral swimmer. The spiral swimmer successfully propelled itself in the viscous fluid ( Figure 1f, and Movie 1, Supporting Information). The propulsion velocity, u, the rotational speed, ω, and the spiral diameter, D spiral , were measured. The experimentally determined dimensionless velocity, u e *, was calculated using these measured values and Equation (8). The dimensionless velocity, u e *, for 12 different swimmers with α ¼ 14 -42 increased with increasing the pitch angle, α (minimum u e * ¼ 0.026 and maximum u e * ¼ 0.077; Figure 1g, dot plots). This increasing tendency was similar to the theoretically calculated dimensionless velocity, u t *, derived from the geometry of the swimmer (pitch angle, α, and spring index, I) (Figure 1g, solid line). The experimentally calculated dimensionless velocity, u e *, was smaller than the theoretically derived dimensionless velocity, u t *. It is considered that the resistive force theory is true only for Re ¼ 0 (experimental conditions: Re ¼ 0.051-0.162), and small inertial effects still occur depending on the size and velocity of the hydrogel swimmer. [23] Therefore, these results indicate that the propulsion velocity dependence on the pitch angle, α, was experimentally verified in our spiral swimmers.
To realize the autonomous geometry change of the spiral swimmer's body, a stimuli-responsive hydrogel was incorporated into the spiral swimmer. Stimuli-responsive hydrogels swell and shrink in response to surrounding stimuli, such as temperature, [25] pH, [26] light, [27] and chemical compounds. [28] We adopted bilayered spiral gels [22] composed of a stimuliresponsive gel and a non-responsive gel (Figure 2a). The expansion and contraction behaviors of the bilayered spiral gel depended on the cross-sectional pattern of the stimuli-responsive hydrogel. [22] To design the dimensionless velocity, u*, of our bilayered spiral swimmer, a finite-element simulation was conducted. In this calculation, swell and shrink behaviors of the stimuli-responsive hydrogel were simplified as an object deformation caused by thermal shrinkage. The gel diameter, D gel , spiral diameter, D spiral , and initial pitch angle, α i , were determined on the basis of the typical shape identified in the previous research [22] (D gel ¼ 300 μm, D spiral ¼ 1050 μm, and α i ¼ 20 ; Figure 2b). Physical parameters of the stimuli-responsive hydrogel and non-responsive hydrogel for our calculation are summarized in Table 1 (determination of these parameters are described in the Supporting Information). Three types of bilayered spiral swimmer models were built with different pattern www.advancedsciencenews.com www.advintellsyst.com angles θ ¼ 0 (inside pattern), 90 (vertical pattern), and 180 (outside pattern), as shown in Figure 2c. The influence of the pattern angle, θ, on the deformation was investigated by the deformation simulation of these bilayered spiral swimmer models. At θ ¼ 0 , the inside pattern spiral swimmer was compressed (Figure 2d, left). On the other hand, the outside pattern spiral swimmer (θ ¼ 180 ) was expanded (Figure 2d, right). These results show that the direction of deformation depends on the pattern angle, θ.
Next, the results of deformation simulation were analyzed toward the deformation direction and the amount of deformation. We evaluated the gap of the spiral, G ¼ p À D gel (Figure 2e, inset), because the deformable range of the bilayered spiral swimmer is limited by the gap G. The spiral swimmer was completely packed and not contracted further when the gap G ¼ 0. Initially, the gap G before deformation was 304 μm (Figure 2e, white bar). After the stimulus, the inside pattern spiral swimmer (θ ¼ 0 and G ¼ 36 μm; Figure 2e, red bar) and the vertical pattern spiral swimmer (θ ¼ 90 and G ¼ 96 μm; Figure 2e, green bar) contracted, whereas the outside pattern spiral swimmer (θ ¼ 180 and G ¼ 2641 μm; Figure 2e, blue bar) expanded. The deformation amount of the outside pattern spiral swimmer (θ ¼ 180 ) was much larger than both of the inside pattern spiral swimmer (θ ¼ 0 ) and the vertical pattern spiral swimmer (θ ¼ 90 ). These results indicate that the deformation direction and the amount of deformation can be designed through the pattern angle, θ.
From the simulation results, the inside pattern (θ ¼ 0 ) and outside pattern (θ ¼ 180 ) spiral swimmers were fabricated for demonstrating the propulsion velocity control. Poly(N-isopropyl acrylamide-co-acrylic acid) (p(NIPAM-co-AAc)), which responds to temperature change, was used as a stimuli-responsive component. To form these bilayered spiral swimmers, we used 6.8% (w/w) magnetic nanoparticles encapsulated in 2.6% (w/w) p(NIPAM-co-AAc) þ 0.4% (w/w) NaAlg solution as a stimuliresponsive layer, and 3% (v/v) fluorescent microbeads (yellow-green fluorescent, 0.2 μm) encapsulated in 1.0% (w/w) NaAlg þ 1.0% (w/w) propylene glycol alginate (PGAlg) solution as a non-responsive layer. The PGAlg was used to adjust the viscosity. Using a Y-connector created by two-photon stereolithography, a bilayered laminar flow was created in the bevel-tip capillary. By adjusting the direction of the laminar flow pattern to the bevel-tip capillary, an inside pattern spiral swimmer (θ ¼ 17 and α i ¼ 32 ) and an outside pattern spiral swimmer (θ ¼ 199 and α i ¼ 21 ) were fabricated (Figure 3a). By applying temperature stimuli (26-46 C), the inside and outside pattern www.advancedsciencenews.com www.advintellsyst.com spiral swimmers gradually deformed to expand and to contract, respectively, with increasing temperature (Figure 3a, and Movies 2 and 3, Supporting Information).
To analyze the deformation of our bilayered spiral swimmer, we compared the measured final pitch angle, α f , with the calculated values on the basis of the simulation results. The final pitch angle of the inside pattern spiral swimmer eventually reached 24 at 46 C, which was close to the simulation results (α f ¼ 22 ; Figure 3b, red circles). On the other hand, the outside pattern spiral swimmer expanded (Figure 3b, blue squares). When a temperature stimulus of 46 C was applied, the final pitch angle of the outside pattern spiral swimmer was 32 , and the value was smaller than the simulation results (α f ¼ 51 ). One of the reasons for these results is that the pattern angle of the fabricated spiral swimmer was slightly different from θ ¼ 180 . These results indicate that the final pitch angle, α f , could be controlled by the strength of the external stimuli.
Finally, we verified the propulsion velocity change by deforming the geometry of the bilayered spiral swimmer caused by applying temperature stimuli. To observe the propulsion velocity change, fabricated bilayered spiral swimmers were placed into a chamber filled with 1 M CaCl 2 solution (experimental conditions: Re ¼ 0.095-0.537). The rotational magnetic field (10 mT and 5 Hz) was applied to the bilayered spiral swimmers. The dimensionless velocity of the inside pattern spiral swimmer decreased from 0.054 (α i ¼ 32 ) to 0.042 (α f ¼ 24 ), as the geometry change was caused by the applied 50 C temperature stimuli (Figure 3c, e, left, and Movie 4, Supporting Information). In contrast, the dimensionless velocity of the outside spiral swimmer increased from 0.037 (α i ¼ 21 ) to 0.061 (α f ¼ 32 ) (Figure 3d,e, right, and Movie 5, Supporting Information). These acceleration and deceleration behaviors had tendencies similar to those of the simulation results (Figure 2f ). The actual velocity showed a similar trend. The actual velocity of the inside pattern swimmer decreased from 424 to 257 μm s À1 , and the actual velocity of the outside pattern swimmer increases from 96 to 200 μm s À1 . Therefore, these results indicate that the propulsion velocity of spiral swimmers can be autonomously controlled by changing the geometry of the spiral swimmer in response to the surrounding stimuli.
Previous research has proposed micromachines with propulsion control implemented by changing the body geometry. [29] However, because the proposed machine could switch between only two different forms, the propulsion velocity only changed between two specific propulsion velocity values. One of the notable potentials of our spiral-shaped microswimmer is that the propulsion velocity is controlled by the applied stimuli, because the geometry of the spiral-shaped body gradually changes depending on the strength of the surrounding stimuli. Bilayered spiralshaped hydrogel could be repeatedly deformed; [22] thus, we think that the propulsion velocity could also be changed repeatedly, because the propulsion velocity change is dependent on the geometry variation. Moreover, the acceleration and deceleration behaviors of the spiral-shaped microswimmers were designed by adjusting both the pitch angle, α, and the pattern angle, θ. From the deformation theory of bimetal, [30] the ratio of stimuliresponsive layer to non-responsive layer is also considered to affect the amount of deformation. The amount of deformation increases as the stimuli layer thickness, reaching a maximum at a ratio of about 2. Therefore, our proposed spiral-shaped microswimmers represent a significant new approach to realize autonomous propulsion velocity control. In contrast, our spiral swimmers also have limitations regarding to the scale of the swimmers. The scale of our swimmer is larger than the typical scale of microorganisms. Because spiral-shaped flagella have a strong advantage for swimming in fluid with a low Reynolds number, a scale of just about a couple micrometers for the microswimmers is preferred. [8] The scale of the swimmer depends on the diameter of the bevel-tip capillary; thus, we considered that smaller swimmers could be fabricated using a bevel-tip capillary with a diameter in the tens of micrometers.
In conclusion, we demonstrated the soft spiral-shaped microswimmer for autonomous swimming control by detecting surrounding environments. The dimensionless velocity of the fabricated bilayered spiral swimmer was successfully changed by applying the thermal stimuli. Our bilayered spiral swimmers could be characterized using the ability to encapsulate various functional materials, [24] including other stimuli-responsive hydrogels. Moreover, complex compartmentalization [31,32] of the spiral swimmer characterized by a laminar flow inside the capillary can also contribute to the optimization of their internal structure and functionality enhancement. The proposed soft spiral-shaped microswimmer can open new avenues for various microscale biochemical applications, such as autonomous soft-robots and soft micro-probes for intricate, miniscule environment.

Experimental Section
See Supporting Information.

Supporting Information
Supporting Information is available from the Wiley Online Library or from the author.