Pancreatic cancer is increasingly common and highly fatal, necessitating effective detection methods (Partyka et al., 2023; Rahib et al., 2014; Sarantis et al., 2020). Diagnosis relies heavily on histological and cytological analysis of masses or lesions (Tyng et al., 2015; Mittal et al., 2023; Balen et al., 1994), often through percutaneous biopsy procedures (Yamao et al., 2005; Crowe et al., 2006; Voss et al., 2000).

Ideally, a biopsy needle should be thin to minimize complications like bleeding and patient discomfort while providing continuous sampling of intact tissue. Fine Needle Aspiration Biopsy (FNAB) and Core Biopsy (CB) are the primary percutaneous methods, with FNAB using thin needles (22–25 G) to retrieve cytological and fluid samples using aspiration and CB employing thicker needles (19–13.5 G) to obtain an intact cylindrical tissue sample, called a core, via a discrete cutting action (May et al., 2018).

Despite their slenderness and ability for continuous sampling, FNAB needles for pancreatic biopsies have been associated with a higher incidence of false negatives compared to CB needles (Liu et al., 2023; Caymaz and Afandiyeva, 2023). Tikkakoski et al. (1992) reported a 13% false negative rate in ultrasound-guided fine-needle pancreatic biopsy. This high rate may stem from needle deflection due to buckling, which can cause the needle to miss the target area, a known issue in breast biopsies (Sabel, 2009). Additionally, aspiration-based methods can result in device clogging, making them unreliable for obtaining intact tissue samples needed for histological evaluation (Madjidyar et al., 2019). The push towards smaller, less invasive tools highlights the need for improved biopsy methods that balance needle size with tissue sampling efficacy.

In an attempt to overcome clogging problems in aspiration-based devices, devices that employ alternative mechanisms for tissue transport have been developed. For instance, Kortman et al. (2023) developed a cable-actuated conveying mechanism for tissue transport that uses the friction between continuously rotating conveying cables and tissue. To overcome buckling problems in thin needles, extensive research is ongoing into lowering the needle’s penetration load by optimizing the needle tip design, introducing needle vibrations, increasing the insertion speed, and increasing skin tension factors (Hirsch et al., 2012; Lenau et al., 2017; Irwin et al., 2021). However, needle designs that can overcome both clogging and buckling problems have yet to be shown.

In nature, the ovipositor of parasitic wasps, used for depositing eggs deep into substrates (King and Vincent, 1995; Sakes et al., 2016), is a remarkable biological structure resembling biopsy needles, as both are long, thin structures designed to penetrate a substrate while simultaneously transporting something (either an egg or tissue) through the lumen. Despite usually having a diameter of only 0.2–0.3 mm, some ovipositors can penetrate up to 20 mm into trees to lay their eggs (Cerkvenik et al., 2017; Quicke and Fitton, 1995). The structure of the ovipositor is different from traditional biopsy needles as it consists of three longitudinally connected valves, one dorsal and two ventral. These valves surround the channel that the egg passes through, as can be seen in Figure 1A. The valves feature a tongue-and-groove mechanism called the olistheter, facilitating a longitudinal sliding motion of the individual valves (Quicke et al., 1994). During drilling into substrates, the olistheter enables the valves to translate in a continuous reciprocating manner, with one valve advancing (i.e., push) whilst the other two valves retract (i.e., pull) in a continuous cycle (Cerkvenik et al., 2017; van Meer et al., 2020). It has been hypothesized that this reciprocating movement gives rise to two functionalities: 1) self-propulsion and 2) friction-based egg transport. These functionalities have inspired the designs of two distinct types of medical devices: self-propelling needles and friction-based tissue transporters.

Integrating both self-propulsion and friction-based tissue transport into a single slender design, inspired by the ovipositor, could offer a novel alternative to current biopsy needles. This design could self-propel to a tissue of interest and use friction-based transport to move the tissue sample through the biopsy needle in two distinct phases: 1) the self-propulsion phase and 2) the tissue-transport phase. The phases and required needle cross-sections during the phases are illustrated in Figures 2A, 2B, respectively.

By combining both the self-propulsion and transport principles of the ovipositor of parasitic wasps, deflection and clogging issues of current thin biopsy needles are negated by relying on friction for both needle insertion and tissue transport. However, combining these functionalities is challenging. A biopsy needle with multiple parallel segments forming a lumen, similar to the ovipositor structure, depends on external friction between the external surface of the needle segments and surrounding tissue for self-propulsion, as well as on internal friction between the tissue sample and the internal surface of the segments for tissue transport. Any interconnecting structure must not interfere with both internal and external contact surfaces. As shown in previous designs, moving away from the ovipositor-inspired tongue-and-groove mechanism is necessary to miniaturize the needle dimensions (Scali et al., 2019; Bloemberg et al., 2022) and to introduce flexibility (de Kater et al., 2021). Former tissue-transport designs have maintained a lumen using external structures that interfere with external surface contact, whereas former self-propelling needles have no lumen to facilitate internal surface contact, highlighting the difficulty of integrating both wasp-inspired functionalities into a slender, flexible biopsy needle.

This study aims to combine the two ovipositor-inspired functionalities, self-propulsion and friction-based tissue transport, into a single, slender biopsy needle design. This approach could offer a viable friction-based alternative to current biopsy needles, particularly for deep biopsies like pancreatic percutaneous biopsies that are currently limited by issues such as buckling and clogging in smaller, aspiration-based needles. Building on previous flexible needle and tissue-transport designs using parallel rods to mimic the valves of the ovipositor, this study will adapt the interconnection method of these needle segments and evaluate the potential of the integrated design as a biopsy needle.

The proposed wasp-inspired biopsy needle design consists of six parallel needle segments that mimic the ovipositor valves. A total number of three outer needle segments would have been sufficient to ensure that the number of retracting needle segments exceeds the number of advancing needle segments. However, to enable a central lumen for tissue transport, we opted for six outer needle segments and a seventh central needle segment that can be removed before the tissue-transport phase. Each needle segment has an equal circular cross-section and a beveled tip. The six needle segments are held in a hexagonal arrangement by a ring passing through slots along the length of the segments, as shown in the cross-sectional view in Figure 3A. This ring-through-slot interconnection restricts the radial translation while allowing longitudinal translation of each needle segment for self-propulsion and tissue transport. The interconnection also prevents rotation of the needle segments around their longitudinal axis, maintaining the orientation of the beveled tips towards the center.

The individual longitudinal translation of the needle segments allows the biopsy needle to mimic the reciprocating movement of the ovipositor valves. Instead of using the 1:2 reciprocating movement sequence of the ovipositor, where one valve is advanced as two are retracted, a 1:5 motion sequence, as used in previous self-propelling designs (Bloemberg et al., 2022) and tissue-transport designs (Sakes et al., 2020; de Kater et al., 2021) is used. The six needle segments are longitudinally translated using this motion sequence over a cycle of six steps. During each step, one needle segment moves forward by a specified distance, called the stroke length (S), while the other five segments move backward by one-fifth of this stroke length ( 1 5 S). After one cycle, the needle segments return to their starting positions, as illustrated in Figure 3B.

The needle segments were designed to be 1 mm in diameter, allowing for the transport of a cylindrical tissue sample, or core, of 1 mm in diameter, which is a common diameter for biopsy samples (Rogowska, 2022). The total diameter of the biopsy needle was 3 mm. A trade-off existed in the number of slots introduced into the needle segments: introducing more slots along the length of the needle could potentially comprise the ability of each needle segment to resist the cutting forces, whilst this simultaneously is advantageous for maintaining the hexagonal arrangement of the entire needle. To balance this, we introduced two slots with a spacing of 100 mm. The first slot was placed near the base of the needle and the second slot was positioned 4 mm from the needle tip to prevent the needle segments from diverging at the tip during self-propulsion. To facilitate the assembly of the needle segments and rings, the slots were not designed to be rectangular but L-shaped to provide an entry point for the rings. Figure 4 shows the concept design and assembly of the needle.

The six needle segments enclose the tissue transportation lumen, which must be either filled or unfilled depending on the biopsy procedure phase (Figure 2B). During the self-propelling phase, the biopsy needle travels to the tissue of interest. The lumen should be filled to prevent a cylindrical piece of tissue from being cut out as the biopsy needle travels into the tissue. To achieve this, a seventh needle segment (indicated in green in Figure 4A) was introduced in the design to fill the lumen when needed. This central needle segment ideally participates in the reciprocating movement during the self-propelling phase and should be able to be removed during the tissue-transport phase, when a lumen is needed.

To achieve the 1:5 motion sequence, the needle segments had to be actuated simultaneously and continuously. Two actuation systems were designed: 1) one motorized unit for testing purposes (Figures 5A, B) and 2) one manual unit for the final prototype to minimize components and create a compact assembly (Figures 5C, D). A rotary cam-and-follower system was used for both actuators (Figures 5A, C, Part 4 in orange). The cams contained a groove, the cam path, guiding the followers (Figures 5A, C, Part 5 in green) to produce continuous linear translation (x-displacement) in the 1:5 motion sequence as the cam rotates. By attaching needle segments to the followers, the linear displacement was transferred to the needle segments, resulting in the 1:5 motion sequence of the biopsy needle overall.

To allow for sufficient space to clamp the needle segments into the followers, the needle segments transition from a larger diameter at the actuation unit to a smaller diameter at the needle tip. Similar to the design presented by Bloemberg et al. (2022), a double cone at the distal end of the actuation unit (Figure 5A, Part 8/Part 9 in blue/yellow; Figure 5C, Part 6/Part 8 in blue, yellow) guides the segments through S-shaped channels, to ensure smooth movement and prevent buckling. At the place where the needle segments diverge there is an opening in the outer cone (Figure 5A, Part 10; Figure 5C, Part 9) to allow the tissue core to exit the biopsy needle after transport.

For the motorized actuation unit, a regular barrel cam was used, where the followers surround the cam path. However, for the manual actuation unit, an inside-out cam design was chosen, with the cam path surrounding the followers. Furthermore, the cam used for manual actuation was star-shaped and approximately the size of a human palm [about 80 mm (Fallahi and Jadidian, 2011)] to allow for sufficient grip and thus easy manual actuation. Both cams shared the same cam path and thus the same stroke distance, resulting in the identical motion sequence of the followers in the longitudinal direction (Figure 5E), and were designed following guidelines from the Machinery’s Handbook [30th Edition, (Oberg et al., 2016)].

The needle prototype consists of seven superelastic straightened nitinol rods, each 1 mm in diameter and 250 mm in length (Titaniumshop, Overijssel, the Netherlands). For the slot extrusion, Wire Electrical Discharge Machining (WEDM), known for its non-contact material removal process, was employed. This method allows for precise slot creation without imposing cutting forces on the segments (Prasad and Chakraborty, 2018; Charles et al., 2024). WEDM was used to create two L-shaped slots (10.25 mm × 0.40 mm) in the distal end of five needle segments. Additionally, a sixth needle segment, i.e., the carrier needle segment, featured smaller L-shaped slots (4.25 mm × 0.40 mm) to carry the rings forward. The length of these slots determines the maximum possible stroke length, which is equal to 4 mm. The seventh central needle segment can simply be inserted and removed easily when necessary. An additional 150 mm of length was added to the central needle segment for this purpose. Furthermore, WEDM was utilized to create the beveled tips of the needle segments (40°). The two interconnecting rings (outer diameter 2.1 mm, inner diameter 1.9 mm, length 2.0 mm) were made of stainless steel. Figure 6A shows the assembled needle excluding the central needle segment and Figure 6B shows the assembled needle including the central needle segment.

The motorized actuation unit integrated off-the-shelf LEGO Technic parts and 3D-printed parts using Silver Metallic PLA on the Fused Deposition Modeling (FDM) printer Ultimaker S5 (Ultimaker, Utrecht, the Netherlands). A LEGO Technic Power Functions Medium motor with a rotational speed of 405 RPM (9V) in a no-load situation was used. A gearbox, created with LEGO gears, was used to adjust the rotational speed of the motor to the desired rotational speeds of the cam for the experiments. The manual actuation unit was entirely 3D printed out of Onyx (Markforged, Waltham, MA, United States), using the FDM printer Markforged Mark Two (Markforged, Waltham, MA, United States). For both actuators, the needle segments were glued into the followers using Loctite 401 Instant Adhesive (Loctite, Westlake OH, United States). Figure 6C and Figure 6D show the assemblies of the motorized and manual actuation units, respectively. Figure 7 illustrates the 1:5 motion sequence of the needle segments during actuation over one cycle.

The goal of the evaluation of the wasp-inspired biopsy needle was twofold: 1) assessing the core-transport capability and 2) assessing the self-propulsion ability. These objectives were addressed in two separate experiments. Experiment 1 focused on core transport while Experiment 2 focused on self-propulsion. Figure 8 gives a schematic overview of both experiments. During testing, the setup involved moving tissue phantoms towards the prototype to enable keeping the prototype stationary. This contrasts a realistic scenario where the needle would advance through tissue, but since the relative movement between the needle and the tissue phantom is the same, it was assumed that this would not influence the test results. Data analysis and visualization were conducted using Python in PyCharm Community Edition 2024.1.1 (JetBrains, Prague, Czech Republic).

As a proof of principle, it was assessed whether the self-propulsion and core transport could be performed sequentially. Using the set-up of Experiment 2, the wasp-inspired biopsy needle was inserted 20 mm into a gelatin block (10 wt%), measuring 80 mm in total length. The motor was turned on, allowing the needle to self-propel over a distance of 45 mm, after which the central needle segment was removed by pulling it out to allow for core extraction over the remaining 15 mm, yielding a core of 15 mm. The near-frictionless air track was then deactivated, immobilizing the gelatin block as the gelatin core was transported from the distal tip to the opening in the outer cone of the actuator. A video showing the proof-of-principle of sequential functioning can be found in the supplementary material.

The proof-of-principle evaluation implied two main findings. It showed that the wasp-inspired biopsy needle was: 1) able to transport a gelatin core, mimicking tissue, using friction-based transport and 2) was able to self-propel. Additionally, it showed that self-propulsion and core transport could be performed sequentially.

The optimal conditions for core transport in our needle design included a 4-mm stroke length, 15-mm core length, theoretical rotational velocity of 24.3 RPM (actual 20.8 RPM), and 10-wt% gelatin composition, achieving a transport efficiency of 69.9% ± 9.1% and a transport rate of 1.16 mm/s ± 0.17 mm/s. Increasing the stroke length not only enhanced the transport rate as expected but also improved efficiency, resulting in a positive impact on the overall transport rate. This phenomenon might be attributed to the advancing needle segment having a higher velocity as the stroke length is increased. A higher velocity could lead to relatively lower friction forces between the advancing needle segment and the gelatin core, leading to more efficient core transport. The flexible wasp-inspired tissue transport design of de Kater et al. (2021) was able to transport tissue with a similar transport rate of 0.83 ± 0.08 mm/s under similar circumstances (horizontal orientation, 10-wt% gelatin, 25 RPM, stroke length of 5.2 mm), despite the larger lumen (3.8 mm). During current CB procedures, tissue cores measuring 1–2 cm in length are typically obtained (Sabel, 2009), which is similar to the core lengths retrieved during our core-transport assessment. Moreover, our needle design can theoretically transport tissue cores up to the entire length of the needle, which is challenging for aspiration-based devices due to clogging issues.

The self-propulsion capability evaluation showed the needle achieving a slip ratio of 0.842 ± 0.042 and a self-propelling rate of 0.257 ± 0.0611 mm/s. In comparison, the self-propelling needle by Scali et al. (2019) (diameter 0.8 mm), also using 10-wt% gelatin, exhibited a lower mean slip ratio of 0.3. The larger diameter of our prototype ( ∅ outer : 3 mm) may contribute to increased gelatin displacement and rupturing around the needle, leading to the formation of a cavity around the needle, thereby reducing the contact area between the needle and surrounding gelatin. A reduction in the contact area between the needle segments and the gelatin will reduce the overall friction force, making it less likely that the friction force of the retracting needle segments can counterbalance the cutting and friction force on the advancing needle segment, causing slip. Miniaturizing the outer dimensions of the needle could potentially mitigate this phenomenon.

The wasp-inspired biopsy needle offers significant advantages over conventional biopsy needles for percutaneous biopsy procedures. It avoids buckling and clogging due to its friction-based propulsion and core-transport methods, allowing for downsizing while maintaining the capability to transport intact tissue samples for histological examination.

During the evaluation, gelatin was chosen as a suitable tissue phantom due to its elasticity that can resemble human tissue, cost-effectiveness, and accessibility. However, gelatin phantoms do not fully capture the complexity of real tissues, particularly concerning the heterogeneity of human tissue, in specific tumor tissue (Polyak, 2011). Due to its homogeneity, gelatin exhibits brittle fracture behavior, leading to sudden rupturing when subjected to mechanical stress (Czerner et al., 2013). This could lead to increased fragmentation during core transport and could lead to cavity formation around the needle during self-propulsion. Furthermore, for needle propulsion experiments, other mechanical properties than the elasticity, for example, the friction coefficient between needle and tissue and the tissue’s shear modulus and ultimate strength, could also be of interest. Transitioning to human tissue poses challenges such as variable stiffness between tissue types (Okamura et al., 2004), complicating self-propulsion. For instance, Bloemberg et al. (2022) reported slip ratios ranging from 0.86 to 0.96 in ex vivo prostate tissue. An interesting next step would therefore be to validate the wasp-inspired biopsy needle in complex tissue models like multi-layered phantoms and ex vivo tissue. When moving towards ex-vivo tissue studies and clinical trials, developing protocols in compliance with the ISO 13485 standard and the Medical Device Regulation 2017/745 will enable us to compare our needle with commercially available alternatives.

The self-propulsion principle of the wasp ovipositor that was implemented in our needle design allowed the needle to self-propel through different gelatin substrates. In order for the self-propulsion principle of the needle to hold, continuous contact between the outer needle surface and the substrate is required. Therefore, during our self-propulsion evaluation, the needle was manually inserted by 20 mm in the gelatin phantom before being actuated. In clinical practice, the needle first has to puncture the skin of the patient, before being able to self-propel through the tissue. The skin introduces a surface stiffness force due to the needle puncturing the skin until the moment of puncture (Okamura et al., 2004). To overcome this, manual insertion of the needle through the skin could be an option using an initial puncture needle, ensuring sufficient contact between the outer needle surface and the surrounding tissue.

The current 3-mm outer diameter of the wasp-inspired biopsy needle prototype represents an improvement over larger former tissue-transport designs [( ∅ outer : 7 mm, ∅ outer : 10 mm) (Sakes et al., 2020; de Kater et al., 2021)] for the use in biopsy procedures, but falls short of standard biopsy needles (18 G, outer diameter of 1.27 mm). Future efforts should therefore focus on miniaturization the needle. The current slot manufacturing method could allow for prototype production on a smaller scale using nitinol rods and stainless steel capillary tubes with smaller diameters. However, further miniaturization may be limited by WEDM, typically using wires of 0.15–0.3 mm (Charles et al., 2024). However, high precision WEDM, capable of handling wires as fine as 0.025–0.1 mm (Slǎtineanu et al., 2020) could, in theory, produce smaller slots and, therefore, aid in further miniaturizing the needle dimensions.

Additionally, given the hexagonal arrangement, reducing the outer diameter will also decrease the lumen diameter, thereby decreasing the amount of tissue that can be retrieved. Since the required amount of tissue differs per diagnostic test (Bhamidipati et al., 2021), to enhance functionality, a relatively large lumen is preferred. To increase the lumen diameter, we propose employing multiple central needle segments or a single central needle segment with a larger diameter.

Navigating around vital structures during percutaneous biopsy procedures, especially near the pancreas where structures like the bowel, liver, kidney, or major vessels can block direct access (Lin et al., 2017), is challenging. Incorporating steerability into biopsy needles can aid in overcoming this challenge. Bevel tips, commonly used in intravascular injections (Smuck et al., 2010), prove effective for maneuvering within the body. Research by Scali et al. (2019) shows successful needle steering using six nitinol rods by simulating an approximated bevel-shaped tip. Alternatively, a prebend central needle segment could be employed to facilitate needle steering. Incorporating either approach into our biopsy needle design could further enhance its functionality.

Our current needle design showcases two use scenarios: (1) needle propulsion, and (2) substrate transportation from the needle tip to the needle base. On top of that, the functionality of our biopsy needle could inspire designs beyond its scope as the motion sequence could also be reversed to facilitate the delivery of substances from the needle base to the needle tip, such as the delivery of medicine, radioactive particles, or high-viscosity hydrogels for cartilage repair, to enhance the delivery of low-viscosity samples compared to current expulsion-based delivery methods (Øvrebø et al., 2022).