Development of a three-microneedle device for hypodermic drug delivery and clinical application

There is a potential use for intradermic or hypodermic drug delivery in skin surgery or aesthetic surgery. Hypodermic delivery with the use of a noninvasive device can be a more useful, reliable, and effective administration route to obtain higher compliance. The authors developed a microneedle device composed of three fine needles (three-microneedle device). The tip of each needle was fabricated with a bevel angle to release a drug broadly into the tissue in a horizontal fashion. In this study, the authors investigated the usefulness of this newly developed three-microneedle device for hypodermic liquid injection, focusing on the optimum insertion depth and the diffusion of injected materials to the tissue. The authors also assessed the efficacy of and patient satisfaction with three-microneedle device injections of botulinum toxin type A for wrinkle reduction in patients with glabellar rhytides. The three-microneedle device yielded consistent results in hypodermal diffusion. On India ink diffusion test and ultrasonographic imaging, three-microneedle device injection showed a broad diffusion in horizontal extension, as compared with usual 31-gauge needle injection. The efficiency and satisfaction of the patients receiving botulinum toxin type A with the three-microneedle device were highly rated. Three-microneedle device delivery enables accurate and broad diffusion of injected substances, thus reducing the total dose and/or injection number of drugs. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.     

Fabrication of a microfluidic device for the compartmentalization of neuron soma and axons

In this video, we demonstrate the technique of soft lithography with polydimethyl siloxane (PDMS) which we use to fabricate a microfluidic device for culturing neurons. Previously, a silicon wafer was patterned with the design for the neuron microfluidic device using SU-8 and photolithography to create a master mold, or what we simply refer to as a "master". Next, we pour the silicon polymer PDMS on top of the master which is then cured by heating the PDMS to 80 degrees C for 1 hour. The PDMS forms a negative mold of the device. The PDMS is then carefully cut and lifted away from the master. Holes are punched where the reservoirs will be and the excess PDMS trimmed away from the device. Nitrogen is used to blow away any excess debris from the device. At this point the devices are now ready for use and can either bonded to corning No. 1 cover glass with a plasma sterilizer/cleaner or can be reversibly bound to the cover glass by simply placing the device on top of the cover glass. The reversible bonding of the device to glass is covered in a separate video and requires first that the device be sterilized either with 70% ethanol or by autoclaving. Plasma treating sterilizes the devices so no further treatment is necessary. It is, however, important, when plasma-treating the devices, to add liquid to the devices within 10 minutes of the plasma treatment while the surfaces are still hydrophilic. Waiting longer than 10 minutes to add liquid to the device makes it difficult for the liquid to enter the device. The neuron devices are typically plasma-bound to cover glass and 0.5 mg/ml poly-L-lysine (PLL) in pH 8.5 borate buffer is immediately added to the device. After a minimum of 3 hours incubating with PLL, the devices are washed with dH2O water a minimum of 3 times with at least 15 minutes between each wash. Next, the water is removed and fresh media is added to the device. At this point the device is ready for use. It is important to remember at this point to never remove all the media from the device. Always leave media in the main channel.     

Factors determining patient choice of device for GH therapy

AIM: To assess the factors determining patient choice of GH device, and whether offering free patient choice improves compliance with GH therapy. METHODS: A prospective cross-sectional study performed on patients offered free choice of GH device in a regional growth clinic. In a subgroup having home delivery, GH compliance was assessed using ampoule counts. RESULTS: 125 patients (74 (59%) male), median (range) 9.30 (1.0-18.3) years were commenced on GH from January 2001 to March 2004, and offered free choice of device. 68 (54%) chose a needled device, and 57 (46%) needle-free. There was no statistical difference in age, sex or diagnostic category between the two groups. Light blue devices were more likely to be chosen by males (p=0.056). Questionnaires giving reasons for choosing a device were available in 40, and a further 50 gave reasons for both choosing a specific device and not choosing others. Other than choice of needled/needle-free device, the factor most likely to determine choice was 'ease of use'. Only 6 (4.8%) subsequently changed device, and compliance remained high but unchanged at approximately 90%. CONCLUSIONS: There are no specific features which determine what GH device a patient will choose. For those units offering free patient choice, a wide range of different devices should be made available.     

A self-powered constant infusion device for use in unrestrained rats

We developed a device that delivers fluid through a catheter at a constant rate and can be used in conscious animals to solve a variety of problems. For example, this device can be used for delivering drugs and maintaining intravascular catheter patency. The device provides infusions at low flows (1.0-1.5 ml/day), so that experimental agents may be administered with minimal volume loading of the rat. Arterial and venous catheter patency is maintained by infusion of heparinized saline through indwelling catheters attached to the device. The catheters exit from the rat in the intrascapular area and are routed through a protective spring to the device, which is suspended above the cage. The catheters may be attached to pressure transducers, blood may be sampled, and injections or infusions may be made without disturbing the rat. Because the device is self-contained, it can be suspended by a fluid-free swivel that rotates through 360 degrees, providing minimal restraint. The device has been used successfully to measure arterial and central venous blood pressures in two studies using rats.     

Termination of early gestation with a vaginal polysiloxane device impregnated with (15S)-15 methyl prostaglandin F2alpha methylester

An investigation of the abortifacient activity of (15S)-15 methyl prostaglandin F2alpha methyl ester released from a vaginal polysiloxane device was performed in eleven pregnant women of 49 days gestation or less. Bleeding and contractions were induced in all women, but only seven aborted their pregnancies. Five subjects received a vaginal device impregnated with 3 mg of drug and two aborted fetal tissue. Six women were given a vaginal device containing 5 mg of drug and five aborted fetal tissue. Ten of the patients had significant side effects, nausea, emesis, diarrhea and chills. Six women expelled the device prior to the termination of therapy. This prostaglandin analogue, when administered from a vaginal polysiloxane device in early gestation was an effective abortifacient but was accompanied by systemic side effects and a high incidence of expulsion of the device prior to its scheduled removal.     

Non-plasma bonding of PDMS for inexpensive fabrication of microfluidic devices

In this video, we demonstrate how to use the neuron microfluidic device without plasma bonding. In some cases it may be desirable to reversibly bond devices to the Corning No. 1 cover glass. This could be due, perhaps, to a plasma cleaner not being available. In other instances, it may be desirable to remove the device from the glass after the culturing of neurons for certain types of microscopy or for immunostaining, though it is not necessary to remove the device for immunostaining since the neurons can be stained in the device. Some researchers, however, still prefer to remove the device. In this case, reversible bonding of the device to the cover glass makes that possible. There are some disadvantages to non-plasma bonding of the devices in that not as tight of a seal is formed. In some cases axons may grow under the grooves rather than through them. Also, because the glass and PDMS are hydrophobic, liquids do not readily enter the device making it necessary at times to force media and other reagents into the device. Liquids will enter the device via capillary action, but it takes significantly longer as compared to devices that have been plasma bonded. The plasma cleaner creates temporary hydrophilic charges on the glass and device that facilitate the flow of liquids through the device after bonding within seconds. For non-plasma bound devices, liquid flow through the devices takes several minutes. It is also important to note that the devices to be used with non-plasma bonding need to be sterilized first, whereas plasma treated devices do not need to be sterilized prior to use because the plasma cleaner will sterilize them.     

The impact of imperfect frame deployment and rotational orientation on stress within the prosthetic leaflets during transcatheter aortic valve implantation

TAVI devices are manufactured with cylindrical frames. However, the frames are rarely cylindrical post-deployment since deformation due to localised under expansion can be induced by calcified material on the native valve leaflets exerting irregular forces upon the frame. Consequently, the leaflets within a deformed TAVI device may undergo elevated stress during operation, which may lead to premature device failure.Using computational analysis a complete TAVI device model was simulated undergoing deployment into an aortic root model derived from CT data for a patient with severe calcific aortic stenosis, followed by a pressure simulated cardiac cycle. The complete analysis was performed eight times, each with the device at a different rotational orientation relative to the native valve, with an increment spacing of 15°.The TAVI device frames consistently featured significant distortions associated with bulky calcified material at the base of the non-coronary sinus. It was found that the average von Mises stress in the prosthetic valves was only increased in one of the cases relative to an idealised device. However, the maximum von Mises stress in the prosthetic valves was elevated in the majority of the cases.Furthermore, it was found that there were preferable orientations to deploy the prosthetic device, in this case, when the prosthetic leaflets were aligned with the native leaflets. As device orientation deviated from this orientation, the stresses in the valve increased because the distance between the prosthetic commissures decreased. This potentially could represent a sufficient increase in stress to induce variation in device lifespan.     

Transcatheter aortic valve replacement: impact of pre-procedural FEops HEARTguide assessment on device size selection in borderline annulus size cases

ObjectivesThe aim of this study is to evaluate device size selection in patients within the borderline annulus size range undergoing transcatheter aortic valve replacement (TAVR) and to assess if pre-procedural patient-specific computer simulation will lead to the selection of a different device size than standard of care.BackgroundIn TAVR, appropriate device sizing is imperative. In borderline annulus size cases no standardised technique for tailored device size selection is currently available. Pre-procedural patient-specific computer simulation can be used, predicting the risk for paravalvular leakage (PVL) and need for permanent pacemaker implantation (PPI).MethodsIn this multicentre retrospective study, 140 patients in the borderline annulus size range were included. Hereafter, device size selection was left to the discretion of the operator. After TAVR, in 24 of the 140 patients, patient-specific computer simulation calculated the most appropriate device size expected to give the lowest risk for PVL and need for PPI. In these 24 patients, device size selection based on patient-specific computer simulation was compared with standard-of-care device size selection relying on a standardised matrix (Medtronic).ResultsIn a significant proportion of the 140 patients (26.4%) a different device size than recommended by the matrix was implanted. In 10 of the 24 patients (41.7%) in whom a computer simulation was performed, a different device size was recommended than by means of the matrix.ConclusionsDevice size selection in patients within the borderline annulus size range is still ambiguous. In these patients, patient-specific computer simulation is feasible and can contribute to a more tailored device size selection.     

Reduction of knee range of motion during continuous passive motion due to misaligned hip joint centre

When using continuous passive motion (CPM) devices, appropriate setting of the device and positioning of the patient are necessary to obtain maximum range of motion (ROM). In this study, the ROMs in both the knee joint and CPM device during CPM treatment were measured using a motion analysis system for three different CPM devices. Additionally, the trajectories of the angles at the knee for hip joint misalignments were evaluated using kinematic models of the three CPM devices. The results showed that discrepancies in ROM between the knee joints and the CPM device settings during CPM treatment were revealed regardless of the CPM device and that the effect of misalignment is dependent on the design of the CPM device. The present technology could be applied for the development of a better design configuration for the CPM device to reduce the discrepancy in ROM at the knee joint.     

Dose Measurements in a 20-J Repetitive Plasma Focus

In this article, the results of X-ray dose measurements executed using thermoluminescent dosimeters in experiments with a very small (20 J) repetitive plasma focus device named SORENA-1 are presented and analyzed. The working gas in these experiments was Argon. Also, pinch formation in experiments with this device has been observed. This device has been designed and constructed in Plasma and Nuclear Fusion Research School of Nuclear Science and Technology Research Institute of Iran. From these results, it is concluded that we can do experiments with this device using Ar as working gas all over the working days of year, and a good symmetry for measured dose around the device has been seen.     

Characteristics of cardiac device infections in the Isala Hospital; a large volume tertiary care cardiology centre

Aims

To determine the frequency, characteristics and risk factors of cardiac device infections in the Isala Hospital.

Methods

We retrospectively studied all patients who underwent cardiac device procedures performed in the cardiac catheterisation lab and the operating room from 2010 to 2012. All patients who developed a cardiac device infection were reviewed for its characteristics.

Results

31/2026 patients developed a cardiac device infection (1.5 %). One (3.2 %) patient died within 30 days of hospitalisation. Device infection rates for procedures in the catheterisation lab and operating room were similar (p = 0.60). Positive cultures were present in 27/31 (87 %) cases. These consisted predominantly of micro-organisms that are part of the skin flora (84 %). The mean time between device procedure and infection was 14 ± 21 months (range 0–79). Cardiac device infection was significantly associated with device revision, (65 % were revisions in patients with device infection vs. 30 % revisions in patients without device infection, p = 0.011) and placement of a left ventricular lead in pacemaker implantations (59 % of patients with vs. 51 % of patients without device infection, p < 0.001).

Conclusion

The frequency of cardiac device infection was 1.5 % with a mortality of 3.2 % within 30 days, which is lower compared with other registries. Cardiac device infections were associated with device revisions and placement of left ventricular leads in pacemaker implantations.     

Reduction of knee range of motion during continuous passive motion due to misaligned hip joint centre

When using continuous passive motion (CPM) devices, appropriate setting of the device and positioning of the patient are necessary to obtain maximum range of motion (ROM). In this study, the ROMs in both the knee joint and CPM device during CPM treatment were measured using a motion analysis system for three different CPM devices. Additionally, the trajectories of the angles at the knee for hip joint misalignments were evaluated using kinematic models of the three CPM devices. The results showed that discrepancies in ROM between the knee joints and the CPM device settings during CPM treatment were revealed regardless of the CPM device and that the effect of misalignment is dependent on the design of the CPM device. The present technology could be applied for the development of a better design configuration for the CPM device to reduce the discrepancy in ROM at the knee joint.     

Development of head docking device for linac-based radiosurgery with a Neptun 10 PC linac

Stereotactic radiosurgery is a method for focused irradiation of intracranial lesions. Linac-based radiosurgery is currently performed by two techniques: couch mounted and pedestal mounted. In the first technique a device is required to affix the patient's head to the couch and neoreover to translate it accurately. Structure of such a device constructed by the authors plus acceptance test performed for evaluation is described in the article.A head docking device has been designed and constructed according to geometry of linac's couch and also desired functions. The device is cornpletely made from aluminum and consists of four major components: attachment bar, lower structure with four moveing accuracy mechanical stability and isocentric accuracy were assessed in the frame of acceptance test.Translating accuracy, mechanical stability and isocentric accuracy were found to be respectively: 1 mm, 1.64 mm and 3.2 mm with accuracy of 95%.According to AAPM report no. 54, a head docking device should translate head with an accuracy of 1 mm; this recommendation has been met. Moreover, we have demonstrated that the isocentric accuracy and mechanical stability of the device are sufficient that the device on confidently be used in stereotactic treatment.     

A device for immobilizing small biological objects under light optical study

A device constructed on the base of a slide and a coverslip is proposed for immobilisation of small biological objects. The device permits performance of gradual and reversible squeezing of live micro-objects. Using the above device it is possible to watch one and the same living object, (for example, a ciliate) repeatedly within a prolonged period of time.     

Development of a Device in Detection of Glaucoma for Rural Eye Care Using Additive Manufacturing and TRIZ

Purpose: The main purpose of this study is to develop a device for the indicative measurement of intraocular pressure (IOP) of eyeball, a key cause for glaucoma. In early diagnosis and treatment of glaucoma accurate measurement of IOP is important. The methods and devices which are available for the measurement of IOP have their own limitations which cause discomfort to the patients during measurement and needs anesthesia. There is a dare need of a device for the measurement of intraocular pressure by making the contact of plunger with closed eyelid eliminating the need of anesthesia and expert ophthalmologist. Method: Additive manufacturing (AM) is an era of technical development and innovation. Developing a device for detecting glaucoma by using AM and TRIZ ‘The theory of inventive problem solving’ (A Collaborative approach) can overcome the disadvantages that classic tonometer have. The field of Ophthalmology will be experiencing a paradigm shift towards the use of collaborative approach of TRIZ with AM. The developed new device was tested on 40 patient’s eye at Government Hospital Bhandara, (M. S.), India. The results of new device were cross verified by expert clinicians using calibrated Schiotz’s tonometer and digital palpation technique. Result: The developed new device was tested on patient’s eye through eyelid and results were compared with calibrated Schiotz’s tonometer. The results from the new device were found in good agreement with results from Schiotz’s tonometer with the average error of 0.033 ± 0.18 (mean ± SD) mm of Hg and mean relative error was -0.0018 ±0.0096 (mean ± SD). Conclusion: There is a substantial need for early detection and diagnosis of glaucoma in rural and remote areas (worldwide). A new device for detection of glaucoma using AM and TRIZ was introduced in this paper and measurements by the new device were by currently well accepted Schiotz’s tonometer. The new device will help the medical practitioners in rural and remote areas for early detection of glaucoma.     

Automated Needle‐free Injection Method for Delivery of Bacterial Suspensions into Citrus Leaf Tissues

A prototype needle‐free device was evaluated for delivery of Xanthomonas citri subsp. citri bacteria into the leaves of cultivars susceptible and resistant to citrus canker. The device delivered a precisely controlled volume of bacterial suspension through infiltration of stomata by injection with pressurized gas. The device produced a uniform inoculation of bacteria into the leaves as measured by the volume of infiltration and diameter of the infiltrated area. No damage to the leaves was observed after inoculation with the automated device, even though a higher number of canker lesions developed compared to a hand‐held needleless syringe injection method. The level of practice needed for operation of the automated device was minimal compared to considerable skill required to perform the hand‐held injection. Results from inoculations with the automated device are in accord with the results with the hand‐held syringe method that demonstrated kumquats are highly resistant to citrus canker while rough lemon and ‘Hamlin’ sweet orange are susceptible.     

Termination of early gestation with a vaginal polysiloxane device impregnated with (15S) -15 methyl prostaglandin F2a methylester

An investigation of the abortifacient activity of (15S) -15 methyl prostaglandin F2_a methyl ester released from a vaginal polysiloxane device was performed in eleven pregnant women of 49 days gestation or less. Bleeding and contractions were induced in all women, but only seven aborted their pregnancies. Five subjects received a vaginal device impregnated with 3 mg of drug and two aborted fetal tissue. Six women were given a vaginal device containing 5 mg of drug and five aborted fetal tissue. Ten of the patients had significant side effects, nausea, emesis, diarrhea and chills. Six women expelled the device prior to the termination of therapy. This prostaglandin analogue, when administered from a vaginal polysiloxane device in early gestation was an effective abortifacient but was accompanied by systemic side effects and a high incidence of expulsion of the evidence prior to its scheduled removal.     

Monitoring Daily QA 3 constancy for routine quality assurance on linear accelerators

The purpose of this study was to evaluate the suitability of the Daily QA 3 (Sun Nuclear Corporation, Melbourne, USA) device as a safe quality assurance device for control of machine specific parameters, such as linear accelerator output, beam quality and beam flatness and symmetry. Measurements were performed using three Varian 2300iX linear accelerators. The suitability of Daily QA 3 as a device for quality control of linear accelerator parameters was investigated for both 6 and 10 MV photons and 6, 9, 12, 15 and 18 MeV electrons. Measurements of machine specific using the Daily QA 3 device were compared to corresponding measurements using a simpler constancy meter, Farmer chamber and plane parallel ionisation chamber in a water tank. The Daily QA 3 device showed a linear dose response making it a suitable device for detection of output variations during routine measurements. It was noted that over estimations of variations compared with Farmer chamber readings were seen if the Daily QA 3 wasn’t calibrated for output and sensitivity on a regular eight to ten monthly basis. Temperature-pressure correction factors calculated by Daily QA 3 also contributed towards larger short term variations seen in output measurements. Energy, symmetry and flatness variations detected by Daily QA 3 were consistent with measurements performed in water tank using a parallel plate chamber. It was concluded that the Daily QA 3 device is suitable for routine daily and fortnightly quality assurance of linear accelerator beam parameters however a regular eight-ten monthly dose and detector array calibration will improve error detection capabilities of the device.     

Nucleic acid purification using microfabricated silicon structures

A microfluidic device has been designed, fabricated and tested for its ability to purify bacteriophage lambda DNA and bacterial chromosomal DNA, a necessary prerequisite for its incorporation into a biosensor. This device consists of a microfabricated channel in which silica-coated pillars were etched to increase the surface area within the channel by 300-600%, when the etch depth is varied from 20 to 50 microm. DNA was selectively bound to these pillars in the presence of the chaotropic salt guanidinium isothiocyanate, followed by washing with ethanol and elution with low-ionic strength buffer. Positive pressure was used to move solutions through the device, removing the need for centrifugation steps. The binding capacity for DNA in the device was approximately 82 ng/cm2 and on average, 10% of the bound DNA could be purified and recovered in the first 50 microl of elution buffer. Additionally, the device removed approximately 87% of the protein from a cell lysate. Nucleic acids recovered from the device were efficiently amplified by the polymerase chain reaction suggesting the utility of these components in an integrated, DNA amplification-based biosensor. The miniaturized format of this purification device, along with its excellent purification characteristics make it an ideal component for nucleic acid-based biosensors, especially those in which nucleic acid amplification is a critical step.     

A pedal corer for the quantitative sampling of sediments and benthic organisms in submerged areas accessible on foot

This paper presents a new device to collect quantitative samples of sediment and benthic organisms. The device is specially designed for sampling with the advantages of box-corer or Eckman dredges in submerged areas that are accessible on foot. The pedal corer is a simple, lightweight, user-friendly device that does not disturb the sediment structure and provides easy access to the sample contained inside the core. With this device, sampling in shallow water zones that are constantly submerged is made easy and sampling time is extended in intertidal zones. Handling editor: J. Saros