Measurement of Blood Dilution during Lancet-Free Blood Sampling.

In this paper, we report on a fluorescent and colorimetric system for measuring the dilution of capillary blood released by a needle-free jet injector. Jet injection uses a high-speed liquid jet to penetrate tissue, and in the process can release capillary blood that can be collected for performing blood tests. In this way, blood sampling can be performed without the use of a lancet. However, any injectate that mixes with the collected blood dilutes the sample and may significantly impact subsequent analyses. By adding the fluorescent marker indocyanine green to the injected liquid, the fraction of injectate mixed into the collected blood can be measured. The incorporation of colorimetry allows our system to also correct for the impact of hematocrit on fluorescence. The results from this system show that it can determine the dilution of blood that has been diluted by up to 10 %, the upper limit of dilution typically observed in lancet-free blood sampling via jet injection.Clinical Relevance- Blood samples can be collected by jet injection without significant dilution, avoiding the need for lancing.

Vacuum-Assisted Needle-Free Capillary Blood Sampling.

BACKGROUND: Poor glycemic management persists among people practicing insulin therapy in relation to type 1 and 2 diabetes despite a clear relationship with negative health outcomes. Skin penetration by jet injection has recently been shown as a viable method for inducing blood release from fingertips. This study examines the use of vacuum to enhance the volume of blood released and quantifies any dilution of the collected blood. METHODS: A single-blind crossover study involving 15 participants, each receiving four different interventions, was conducted wherein each participant served as their own control. Each participant experienced fingertip lancing and fingertip jet injection, both with and without applied vacuum. Participants were divided into three equal groups to explore different vacuum pressures. RESULTS: This study found that glucose concentration in blood collected under vacuum following jet injection and lancing were equivalent. We found that applying a 40 kPa vacuum following jet injection produced a 35-fold increase in the collected volume. We determined the limited extent to which the injectate dilutes blood collected following jet injection. The mean dilution of blood collected by jet injection was 5.5%. We show that jet injection is as acceptable to patients as lancing, while being equally suited for conducting glucose measurements. CONCLUSIONS: Vacuum significantly enhances the volume of capillary blood released from the fingertip without any difference in pain. The blood collected by jet injection with vacuum is equivalent to that from lancing for glucose measurement purposes.

Soft Electromagnetic Motor and Soft Magnetic Sensors for Synchronous Rotary Motion.

To create fully-soft robots, fully-soft actuators are needed. Currently, soft rotary actuator topologies described in the literature exhibit low rotational speeds, which limit their applicability. In this work, we describe a novel, fully-soft synchronous rotary electromagnetic actuator and soft magnetic contact switch sensor concept. In this study, the actuator is constructed using gallium indium liquid metal conductors, compliant permanent magnetic composites, carbon black powders, and flexible polymers. The actuator also operates using low voltages (<20 V, ≤10 A), has a bandwidth of 10 Hz, a stall torque of 2.5-3 mN·m, and no-load speed of up to 4000 rpm. These values show that the actuator rotates at over two orders-of-magnitude higher speed with at least one order-of-magnitude higher output power than previously developed soft rotary actuators. This unique soft rotary motor is operated in a manner similar to traditional hard motors, but is also able to stretch and deform to enable new soft robot functions. To demonstrate fully-soft actuator application concepts, the motor is incorporated into a fully-soft air blower, fully-soft underwater propulsion system, fully-soft water pump, and squeeze-based sensor for a fully-soft fan. Hybrid hard and soft applications were also tested, including a geared robotic car, pneumatic actuator, and hydraulic pump. Overall, this work demonstrates how the fully-soft rotary electromagnetic actuator can bridge the gap between the capabilities of traditional hard motors and novel soft actuator concepts.

Minimally invasive capillary blood sampling methods.

INTRODUCTION: Whole blood samples, including arterial, venous, and capillary blood, are regularly used for disease diagnosis and monitoring. The global Covid-19 pandemic has highlighted the need for a more resilient screening capacity. Minimally invasive sampling techniques, such as capillary blood sampling, are routinely used for point of care testing in the home healthcare setting and clinical settings such as the Intensive Care Unit with less pain and wounding than conventional venepuncture. AREAS COVERED: In this manuscript, we aim to provide a overview of state-of-the-art of techniques for obtaining samples of capillary blood. We first review both established and novel methods for releasing blood from capillaries in the skin. Next, we provide a comparison of different capillary blood sampling methods based on their mechanism, testing site, puncture size, cost, wound geometry, healing, and perceptions of pain. Finally, we overview established and new methods for enhancing capillary blood collection. EXPERT OPINION: We expect that microneedles will prove to be a preferred option for paediatric blood collection. The ability of microneedles to collect a capillary blood sample without pain will improve paediatric healthcare outcomes. Jet injection may prove to be a useful method for facilitating both blood collection and drug delivery.

Jet-Induced Blood Release From Human Fingertips: A Single-Blind, Randomized, Crossover Trial.

BACKGROUND: Lancet pricks are often poorly received by individuals with diabetes; jet injection may allow lancet-free blood sampling. We examine whether the technique of jet injection can release sufficient blood from the fingertip to enable measurement of blood glucose concentration. In addition, we assess the effect of jet shape and cross-sectional area on fluid release, blood dilution, and perceived pain. METHODS: A randomized, single-blind, crossover study was conducted on 20 healthy volunteers who received interventions on four fingertips: a lancet prick, and jet injection of a small quantity of saline solution through three differently shaped and sized nozzles. Released fluid volume, blood concentration, and glucose concentration were assessed immediately after the intervention. Pain perception and duration, and any skin reactions, were evaluated both immediately and 24 hours after the intervention. RESULTS: Jet injection released sufficient blood from the fingertip to conduct a glucose measurement. A slot-shaped nozzle released the most blood, although less than a lancet, with slightly higher pain. The blood glucose levels estimated from the extracted fluid showed a mean absolute percentage error of 25%. There was no consistent evidence that a jet injection leads to different skin reactions at the intervention site relative to a lancet prick. CONCLUSIONS: Fingertip penetration by jet injection can release a volume of fluid sufficient for blood glucose measurement. Jet injection with a slot-shaped nozzle and/or a nozzle with larger outlet area helps to release more fluid. This technique may enable blood sampling, glucose concentration measurement, and insulin delivery to be performed in a single device.

Jet injection needle-free dental anaesthesia: Initial findings.

OBJECTIVES: We evaluated patient preference and reported levels of anxiety and discomfort of participants treated with a new needle-free electric motor-driven device vs. conventional local anaesthetic for dental extractions in a proof-of-principle study. Healing and response of gingival tissues to injection were also evaluated at 1, 3- and 7-days post-procedure. METHODS: After informed consent, eight participants who required bilateral maxillary extractions were included in the trial. The side and order of placement for the needle-free and conventional anaesthetic were randomized. The same operator delivered anaesthesia and ensured teeth were anaesthetized on both sides. Another operator, unaware of order and type of anaesthesia placed, performed the extractions. RESULTS: Participant's average discomfort scores were low for both techniques, and lower for the needle-free injection at all timepoints. Needle-free local anaesthesia was the preferred technique by most participants at most timepoints. The average volume of anaesthetic dispensed was similar between techniques. Successful anaesthesia with the needle-free device was achieved in 6 out of 8 participants. Healing of the extraction sockets and adjacent oral mucosa progressed normally for all participants, with no evidence of infection, trauma or hematoma in the injection sites of the test and conventional sides. CONCLUSIONS: The needle-free local anaesthetic technique investigated achieved sufficient anaesthesia for tooth extractions in the maxilla in 75% of the subjects. A larger clinical trial is needed to further validate the technique tested and to investigate whether needle-free local anaesthesia can be successfully applied to the provision of restorative therapy. CLINICAL SIGNIFICANCE: The results of this study can be used by clinicians treating patients who suffer from dental anxiety and needle-phobia.

Jet-Induced Tissue Disruption for Blood Release.

OBJECTIVE: Needle-free jet injection is a drug delivery technique that uses the momentum of the fluid drug to break through the skin. This technique has recently also been applied to blood release, aiming to collect samples from capillaries in the skin without needing a lancet prick. This work provides new information about the wound geometry and tissue disruption caused by shallow jet injection with circular-shaped and slot-shaped jets. METHODS: We use histological analysis to compare the disruption of tissue, including blood vessels, caused by lancet-pricking and jet injection with a circular-shaped jet and a lancet-inspired slot-shaped jet. RESULTS: Intradermal injection into porcine skin using a slot-shaped jet disrupted more vascular endothelium in the tissue than a circular-shaped jet and did so at a smaller penetration depth with smaller wound volume. Our results suggest that shallow jet injections may have the potential to release more capillary blood than a lancet prick. CONCLUSION: These findings demonstrate that a reversible jet injector might be used in diabetes management as a device to release and collect blood samples, in addition to being used to deliver insulin. SIGNIFICANCE: Tissue disruption is crucial to consider when using jet injection to deliver drugs and release capillary blood.

Shoulder Joint Stiffness in a Functional Posture at Various Levels of Muscle Activation.

OBJECTIVE: In this study, we present a method to quantify the mechanics of the shoulder joint in a functional posture, in two degrees of freedom: internal/external rotation and horizontal abduction/adduction. METHODS: We performed experiments on 15 healthy participants using a custom perturbation robot. Perturbations were applied in internal/external rotation and horizontal abduction/adduction, whilst participants applied varying levels of joint torque. System identification techniques were used to quantify the mechanical properties of the shoulder joint at various levels of muscle contraction, including; stiffness, viscous damping, and inertia parameters, natural frequency, and damping parameter. We compared the shoulder mechanical properties between dominant and non-dominant limbs. RESULTS: The mean stiffness increased 4.8 times in external rotation, and 6.25 times in internal rotation as a result of contraction to 8 Nm. It increased 2.8 times in adduction and 4.6 times in abduction as a result of contraction to 16 Nm. The mean viscous damping increased 3 times in external rotation, 2.8 times in internal rotation as a result of contraction to 8 Nm. It increased 1.6 times in adduction and 2.25 times in abduction as a result of contraction to 16 Nm. CONCLUSION: Joint stiffness, viscous damping and natural frequency all increased with the level of shoulder contraction torque, whereas the damping parameter remained unchanged. No differences were observed between dominant and non-dominant limbs. SIGNIFICANCE: We have presented a method to characterize the mechanical properties of the shoulder complex during various activation states, which has application as a diagnostic and assessment tool for shoulder pathology.

Ankle torque forecasting using time-delayed neural networks.

A method for ankle torque prediction ahead of the current time is proposed in this paper. The mean average value of EMG signals from four muscles, alongside the joint angle and angular velocity of the right ankle, were used as input parameters to train a time-delayed artificial neural network. Data collected from five healthy subjects were used to generate the dataset to train and test the model. The model predicted ankle torque for five different future times from zero to 2 seconds. Model predictions were compared to torque calculated from inverse dynamics for each subject. The model predicted ankle torque up to 1 second ahead of time with normalized root mean squared error of less than 15 percent while the coefficient of determination was over 0.85.Clinical Relevance- the potential of the model for predicting joint torque ahead of time is helpful to establish an intuitive interaction between human and assistive robots. This model has application to assist patients with neurological disorders.

System Identification to Characterise Shoulder Joint Dynamics in Two Degrees of Freedom.

In this study, we present a new design of a shoulder perturbation robot that can characterise the dynamics of the shoulder in two degrees of freedom. It uses two linear electric motors to perturb the shoulder joint in internal/external rotation and abduction/adduction, and force and position sensors to measure the corresponding torque and angular displacement about the joint. System identification techniques are used to estimate the dynamics of the muscles around the joint. The advantage our apparatus offers over the existing ones is that it can efficiently transfer torque to the joint and measure its dynamics separately with minimal interference from soft tissues. We verified that the apparatus can accurately estimate joint dynamics by conducting tests on a phantom of known properties. In addition, experiments were conducted on a human participant. It has been demonstrated that the measured dynamics of participant's arm are repeatable. The potential impact of our apparatus is to be used in clinic as a diagnostic tool for rotator cuff injuries.

Blood Collection from The Porcine Ear Using a Jet Injector.

We present a new lancet-free method of capillary blood collection for the measurement of blood glucose concentration using a needle-free jet injector. This technique is tested on living animals and directly compared to the current best practice, lancet prick. Shallow jet injection into porcine outer-ear was performed using a portable needle-free jet injector with a slot-shaped nozzle. The jet injections presented used about 25 µL of injectate to penetrate porcine skin to about 1.4 mm, which is within the WHO standards for capillary blood sampling. The blood and fluid released by the jet injections and lancet pricks was collected. The volume and colour of these samples were analysed. The results demonstrate that jet injection is a feasible technique for the collection of capillary blood, despite the small volume of blood samples retrieved from all four pigs. Jet injection may be used in the future to retrieve capillary blood samples from human fingertips.

Spatially resolved diffuse imaging for high-speed depth estimation of jet injection.

We investigate the use of spatially resolved diffuse imaging to track a fluid jet delivered at high speed into skin tissue. A jet injector with a short needle to deliver drugs beneath the dermis, is modified to incorporate a laser beam into the jet, which is ejected into ex vivo porcine tissue. The diffuse light emitted from the side and top of the tissue sample is recorded using high-speed videography. Similar experiments, using a depth-controlled fiber optic source, generate a reference dataset. The side light distribution is related to source depth for the controlled-source experiments and used to track the effective source depth of the injections. Postinjection X-ray images show agreement between the jet penetration and ultimate light source depth. The surface light intensity profile is parameterized with a single parameter and an exponential function is used to relate this parameter to source depth for the controlled-source data. This empirical model is then used to estimate the effective source depth from the surface profile of the injection experiments. The depth estimates for injections into fat remain close to the side depth estimates, with a root-mean-square error of 1.1 mm, up to a source depth of 8 mm.

Classification of diffuse light emission profiles for distinguishing skin layer penetration of a needle-free jet injection.

In this work, a system is developed for tracking the skin layer to which a needle-free jet injection of fluid has penetrated by incorporating a laser beam into the jet, and measuring the diffuse light emitted from skin tissue. Monitoring the injection in this way offers the ability to improve the reliability of drug delivery with this transdermal delivery method. A laser beam, axially aligned with a jet of fluid, created a distribution of diffuse light around the injection site that varied as the injection progressed. High-speed videography was used to capture the diffuse light emission from laser-coupled jet injections into samples of porcine skin, fat, and muscle. The injection produced a distribution of diffuse light around the injection site that varied as the injection descended. A classifier, trained to distinguish whether the light source was located in the fat or muscle from surface intensity profile measurements, correctly identified the injected layer in 97.2 % of the cases when cross-examined against estimates using the light distribution emitted from the side of the sample.

Subcutaneous nicotine delivery via needle-free jet injection: A porcine model.

Subcutaneous delivery of nicotine was performed using a novel electrically-operated needle-free jet injector, and compared to hypodermic needle delivery in a porcine model. Nicotine was delivered as a single, one-milligram dose into the abdominal skin, formulated as a 50 microliter aqueous solution. Plasma levels of nicotine and cotinine, its main metabolite, were then monitored over 2 h, following which the injection site was excised for histological examination. No irritation or tissue damage were found at the injection sites, and the jet-injected nicotine exhibited comparable absorption into the systemic circulation to that injected using a conventional needle and syringe. The needle-free jet injection of nicotine is a promising and well tolerated method. The data presented from this porcine model will support a first in human trial towards a new promising nicotine replacement therapy.

Viscous Heating Assists Jet Formation During Needle-Free Jet Injection of Viscous Drugs.

OBJECTIVE: Jet injectors use a high-pressure liquid jet to pierce the skin and deliver drug into underlying tissues. This jet is formed through a short, narrow orifice; the geometry of the orifice and the properties of the fluid affect the nature of the flow. We aimed to discover information about the turbulent and viscous processes that contribute to pressure loss and flow patterns during jet injection. METHODS: We used computational fluid dynamics methods and experimental observation to investigate the effects of nozzle geometry, fluid viscosity, and viscous heating on jet production. We experimentally verified the temperature change of the jet during ejection, using an infrared camera. RESULTS: Our models accurately predict the average jet speed produced for two example nozzle geometries over two orders of magnitude of viscosity. The models reveal the previously unreported importance of viscous heating in the formation of the jet. Temperatures >65 °C were predicted at the edge of the flow as a result of viscous heating. These caused a significant local reduction in viscosity and effectively allowed the fluid to lubricate itself. Our experiments confirmed changes in mean jet temperature of up to 2.5 °C, which are similar to those predicted by our model (∼2.8 °C). CONCLUSION: These results reveal the importance of the viscous heating properties of a fluid in the formation of high-speed jets for drug delivery. SIGNIFICANCE: This property is crucial to consider when formulating new drugs for needle-free jet injection.

Laterally Dispersing Nozzles for Needle-assisted Jet Injection.

Most transdermal drug delivery systems are designed to inject drugs through the skin in a direction normal to the skin surface. However, in some applications, such as local anaesthesia, it is desirable to disperse the drug in a direction parallel to the surface of the skin. In this paper we present nozzles for needle-assisted jet injection that are designed to laterally disperse the fluid drug at a chosen depth in tissue. These nozzles were manufactured by laser machining holes in the walls of 0.57 mm (24 G) hypodermic needles, and sealing the ends of the needles. An existing controllable jet injection system was used to test the nozzles. High-speed video recordings were taken to examine the shape of the high-speed jets emitted from the orifices, and jet injections into post mortem porcine tissue were performed to evaluate the resulting dispersion pattern. These injections demonstrated the ability of these nozzles to achieve a widely spread dispersion at a depth of 3 mm to 4 mm in tissue. We observed that the widest dispersion occurred at the same depth as the orifices, and dispersion was greater in the direction of the jets. Further investigation, including an in vivo study, is now required to evaluate whether this technique can reduce the time, cost or pain associated with transdermal local anaesthetic delivery.

Power-efficient controlled jet injection using a compound ampoule.

We present a new mechanism for achieving needle free jet injection that significantly reduces the power required to perform a given injection. Our 'compound ampoule' produces two phases of jet speed under a constant force input by changing the effective piston area part-way through the injection. In this paper we define the benefits associated with a compound ampoule, relative to those of the conventional single piston design, by developing expressions for the power and energy required to perform an injection. We demonstrate that a compound ampoule can reduce the maximum input power required to perform a jet injection to less than one fifth of that previously required, enabling motors of less than half the mass to perform the same injection. We then detail the development of a prototype compound ampoule injector. Results from testing of this prototype demonstrate the function of a compound ampoule and verify the expected reduction in the required power and energy. Injections into post mortem porcine tissue confirm that our compound ampoule prototype can achieve the delivery of 1 mL of liquid into post-mortem tissue at least as effectively as a conventional ampoule. This approach will advance progress toward light-weight and power-efficient needle-free jet injectors for transdermal drug delivery.

The effect of jet speed on large volume jet injection.

Jet injection presents a promising alternative to needle and syringe injection for transdermal drug delivery. The controllability of recently-developed jet injection devices now allows jet speed to be modulated during delivery, and has enabled efficient and accurate delivery of volumes up to 0.3 mL. However, recent attempts to inject larger volumes of up to 1 mL using the same methods have highlighted the different requirements for successful delivery at these larger volumes. This study aims to establish the jet speed requirements for delivery of 1 mL of liquid using a controllable, voice coil driven injection device. Additionally, the effectiveness of a two-phase jet speed profile is explored (where jet speed is deliberately decreased toward the end of the injection) and compared to the constant jet speed case. A controllable jet injection device was developed to deliver volumes of 1 mL of liquid at jet speeds >140 m/s. This device was used to deliver a series of injections into post-mortem porcine tissue in single and two-phase jet speed profiles. Single-phase injections were performed over the range 80 m/s to 140 m/s. Consistent delivery success (>80% of the liquid delivered) was observed at a jet speed of 130 m/s or greater. Consistent penetration into the muscle layer coincided with delivery success. Two-phase injections of 1 mL were performed with a first phase volume of 0.15 mL, delivered at 140 m/s, while the injection of the remainder of fluid was delivered at a second phase speed that was varied over the range 60 m/s to 120 m/s. Ten two-phase injections were performed with a second phase speed of 100 m/s producing a mean delivery volume of 0.8 mL ±â€¯0.2 mL, while the single-phase injections at 100 m/s achieved a mean delivery volume of 0.4 mL ±â€¯0.3 mL. These results demonstrate that a reduced jet speed can be used in the later stages of a 1 mL injection to achieve delivery success at a reduced energy cost. We found that a jet speed approaching 100 m/s was required following initial penetration to successfully deliver 1 mL, whereas speeds as low as 50 m/s have been used for volumes of <0.3 mL. These findings provide valuable insight into the effect of injection volume and speed on delivery success; this information is particularly useful for devices that have the ability to vary jet speed during drug delivery.

High-speed X-ray analysis of liquid delivery during jet injection.

The effect of varying velocity during jet injection on the dispersion of fluid into tissue is investigated using a custom-built X-ray imaging system. Injections are performed into ex-vivo porcine abdominal tissue using a voice coil actuated injection device. Single velocity and two-phase velocity injections reveal the complex nature of the dispersion of the fluid jet in layered tissue and highlight the effects of changing the jet velocity following the initial penetration of the liquid into the tissue.

Four-Dimensional Imaging of Cardiac Trabeculae Contracting In Vitro Using Gated OCT.

Cardiac trabeculae are widely used as experimental muscle preparations for studying heart muscle. However, their geometry (diameter, length, and shape) can vary not only among samples, but also within a sample, leading to inaccuracies in estimating their stress production, volumetric energy output, and/or oxygen consumption. Hence, it is desirable to have a system that can accurately image each trabecula in vitro during an experiment. To this end, we constructed an optical coherence tomography system and implemented a gated imaging procedure to image actively contracting trabeculae and reconstruct their time-varying geometry. By imaging a single cross section while monitoring the developed force, we found that gated stimulation of the muscle was sufficiently repeatable to allow us to reconstruct multiple contractions to form a four-dimensional representation of a single muscle contraction cycle. The complete muscle was imaged at various lengths and the cross-sectional area along the muscle was quantified during the contraction cycle. The variation of cross-sectional area along the length during a contraction tended to increase as the muscle was contracting, and this increase was greater at longer muscle lengths. To our knowledge, this is the first system that is able to measure the geometric change of cardiac trabeculae in vitro during a contraction, allowing cross-sectional stress and other volume-dependent parameters to be estimated with greater accuracy.