Application Articles

At Kaha Sciences, we are proud to have been at the forefront of innovation and improvements in small animal telemetry systems for preclinical research.  Now we have taken this innovation one step further in utilising our patented wireless power technology to develop our soon to be released, first fully implantable optogenetics stimulating and recording telemeter for rats.  This exciting new product will allow customers to apply optogenetics stimulation and biopotential recording in long-term experiments without the restriction of battery life.  Additionally, the user has access to all the other beneficial aspects of the Kaha Sciences rat telemetry system, including Cohousing, dual implantation and recording away from the SmartPad.

Key Features and Advantages include:

• Unlimited power provides opportunity for long-term studies (weeks to months)
• Unlimited power provides unrestricted stimulation patterns
• Single implant allows biopotential recording during optogenetics stimulation
• Fully implantable device – normal unrestricted animal behaviour and movement with no tethers
• Fully implantable device – reduces probability of infection at cable exit sites
• Fully implanted device – reduction in cost of maintenance and replacement of tethers
• Software controlled, user defined stimulation parameters

Optogenetics is a relatively recent technique which uses light to precisely control neuronal cells that have been transfected with a specific channelrhodopsin¹.  Compared to conventional electrical stimulation, optogenetics reduces the activation of neighbouring cells ensuring that stimulation is highly targeted and results in specific physiological and behavioural effects.  Despite significant advances in the transfection of channelrhodopsins into specific cell types, the technology for the provision of light for stimulation still mainly relies on tethered or headmounted systems.  These systems have several disadvantages including:

• increased susceptibility to infection
• impacts normal physiology and behaviour
• restriction of experimental duration and protocols due to restraint and/or limited battery-life
• additional costs of tether maintenance and replacement.

The novel Kaha Sciences Optogenetics Biopotential telemeter (TR58AB) is the first fully implantable stimulating and recording device for rats (>175g) which consists of a blue LED (460nm), 35cm optical fibre for light delivery and 25cm biopotential leads for recording EEG, EMG or ECG in response to light stimulation (Fig 1A).  The TR58AB telemeter is compatible with Kaha Sciences existing hardware and user-defined stimulation parameters are completely software controlled, with our ConfigSoft program (Fig 1B).  Like all Kaha rat telemeters, the optogenetics telemeter is free from the restriction of battery life as they are wirelessly powered from the TR181 SmartPad, supporting 24/7 continuous home-cage recording and now long-term stimulation.

In vitro testing has shown the TR58AB to successfully activate transfected neurons in brain slices² and in vivo testing in a rat Parkinsonian model has shown that the optical fibre is suitable for chronic implantation and light delivery.  The new TR58AB is ideal for application and studies in numerous physiological and neuroscience research projects, including heart pacing, seizure suppression and reducing abnormal motor symptoms.  The tool is ideally suited to extend the opportunities for existing researchers using optogenetics and wanting to be able to conduct extended stimulation protocols and collect quantitative biopotential data without the restriction of battery power and/or tethers.

If you would like any additional information regarding the Kaha Sciences Optogenetics or any telemetry solutions please contact us.

1. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8, 1263–1268 (2005).
2. Chen, F. B. Feasibility of a fully implantable optogenetic system for chronic animal studies. (University of Auckland, 2017).

Accuracy, reliability and sensitivity are essential when measuring any physiological pressure.  Traditional methods of acute and chronic pressure measurement have used gel- or fluid-filled catheters which limits and compromises data collection. At Kaha, we utilize the latest wireless power technology integrated with the accuracy, reliability and sensitivity of the 2 Fr Millar Mikro-Tip® solid-state sensor (Fig 1A). This allows Kaha Sciences rat telemeters to be used for short- and long-term measurement of physiological pressures including arterial pressure, left ventricular pressure and intracranial pressure (ICP).

The following table highlights some of the advantages of having a solid-state sensor in a catheter tip:

At Kaha, we have a range of pressure telemeters available from the single pressure TRM54P and dual pressure TRM54PP, to our combined biopotential/pressure telemeter, TRM54PB.  For those studying cardiovascular control our sympathetic nerve activity and pressure TRM56SP telemeter has been very useful.  The telemeters come standard with a 9cm catheter, however, custom lengths of 15cm or 25cm are available to suit and support different applications and pressure measuring sites.  The sensitivity and accuracy of our solid-state sensor pressure telemeters is exemplified in a publication by Thakkar et. al., who measured intracranial pressure (Fig 1C) and arterial blood pressure simultaneously using our dual pressure telemeter (TRM54PP2509) in a study of stroke¹.  Also, Hunter et al were able to make highly accurate intravesical (bladder) pressure recordings using our single pressure telemeter (TRM54P)².

The incorporation of the Millar Mikro-Tip® pressure sensor into the Kaha Sciences pressure telemeters is a further example of our desire to push the boundaries of telemetry technology and ensure our customers can record highly accurate, repeatable data.  For more information about the Kaha Sciences telemetry systems please contact us.

1. Thakkar, P. et al. Hypertensive Response to Ischemic Stroke in the Normotensive Wistar Rat: Mechanisms and Therapeutic Relevance. Stroke 50, 2522–2530 (2019).
2. Hunter, D. V., Holland, S. D. & Ramer, M. S. Preserved Adrenal Function After Lumbar Spinal Cord Transection Augments Low Pressure Bladder Activity in the Rat. Front. Physiol. 9, 1239 (2018).

Kaha Sciences telemetry solutions combine wireless power and state of the art pressure sensor technology to provide unrivalled accuracy and long-term recording in cardiovascular research.

• Telemeters transmit data to the TR181 SmartPad receivers on one of 40 independent frequency channels to ensure no data cross talk
• SmartPads provide wireless inductive power to telemeters to remove the reliance on a battery and support 24/7 recording

Pressure

Kaha Sciences rat pressure telemeters use the Millar Mikro-Tip® solid state sensor technology, at the catheter tip to allow high fidelity, accurate and repeatable pressure recordings. The 2 Fr (0.66 mm) sensor can record a range of pressures including; arterial blood pressure, venous pressure and ventricular pressure. Telemeters are available with single (TRM54P) or dual (TRM54PP) catheters in lengths of 9, 15 or 25cm so customers can tailor their experiment and record up to two pressures with one telemeter.

The quality and accuracy of the signal allows confidence in basic feature extraction across animals (e.g. systolic, diastolic) but also facilitates more complex analysis such as spectral analysis and cardiac output from BP and dP/dt calculations from LVP.

Publications:

• Stehlin, E. et al. Chronic measurement of left ventricular pressure in freely moving rats. J. Appl. Physiol. 115, 1672–1682 (2013).
• Han, J.-C. et al. Left-Ventricular Energetics in Pulmonary Arterial Hypertension-Induced Right-Ventricular Hypertrophic Failure. Front. Physiol. 8, 1115 (2018).
• Griffiths, P. R. et al. Blockade of Rostral Ventrolateral Medulla Apelin Receptors Does Not Attenuate Arterial Pressure in SHR and L-NAME-Induced Hypertensive Rats. Front. Physiol. 9, 1488 (2018).

ECG

Biopotential telemeters (TR50B and TR50BB) allow the long-term recording of ECG, EMG or EEG in freely moving rats. Our wireless power technology supports long-term, continuous recording at high sampling rate (2kHz) which is ideal for monitoring spontaneous pathophysiological activity, such as ectopic beats or the generation of arrhythmia. The TRM54PB telemeter also allows customers to combine ECG and pressure measurements from the same animal to assess cardiac and cardiovascular function.

Publications:

• Kim, N. K., Wolfson, D., Fernandez, N., Shin, M. & Cho, H. C. A rat model of complete atrioventricular block recapitulates clinical indices of bradycardia and provides a platform to test disease-modifying therapies. Sci. Rep. 9, 6930 (2019).
• Zhang, D. et al. Reduced N‐Type Ca ²⁺ Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis. J. Am. Heart Assoc. 7, (2018).

Sympathetic Nerve Activity (SNA)

The TRM56SP telemeters allows users to simultaneously record concurrent blood pressure and SNA from the same animal. This is particularly useful in studies of the development of hypertension and cardiovascular control. The input range of the SNA leads is ±60µV making it ideal for activity recording from fine, peripheral autonomic nerves.

Publications:

• McBryde, F. D., Liu, B. H., Roloff, E. V., Kasparov, S. & Paton, J. F. R. Hypothalamic paraventricular nucleus neuronal nitric oxide synthase activity is a major determinant of renal sympathetic discharge in conscious Wistar rats. Exp. Physiol. 103, 419–428 (2018).
• Salman, I. M., Sarma Kandukuri, D., Harrison, J. L., Hildreth, C. M. & Phillips, J. K. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease. Front. Physiol. 6, (2015).

Tissue oxygen

The TR57Y tissue oxygen telemeter is the only device available on the market that can measure tissue oxygen concentration from conscious rats, in real time. The telemeter uses a stable carbon paste electrode and can measure local ischemia and tissue metabolic activity in the kidney and brain. Combined with our wireless power technology researchers have been able to assess circadian variability in kidney tissue oxygen thanks to the ability to record 24/7.

Publications:

• Adamovich, Y. et al. Oxygen and Carbon Dioxide Rhythms Are Circadian Clock Controlled and Differentially Directed by Behavioral Signals. Cell Metab. 29, 1092-1103.e3 (2019).
• Emans, T. W., Janssen, B. J., Joles, J. A. & Krediet, C. T. P. Circadian Rhythm in Kidney Tissue Oxygenation in the Rat. Front. Physiol. 8, (2017).

For more information please contact us.

Kaha Sciences fully implantable rat and mouse telemetry solutions combine state of the art technologies to provide unrivalled accuracy and long-term recording in neuroscience research.

• Telemeters transmit data to the TR181 SmartPad (rat) or MT110 tBase (mice) receivers on one of 40 independent frequency channels to ensure no data cross talk
• SmartPads and tBases provide wireless inductive power to telemeters to remove the reliance on a battery and support 24/7 recording

Intracranial Pressure

Kaha Sciences rat pressure telemeters use the Millar Mikro-Tip® solid state sensor technology, at the catheter tip to accurately measure small pressures, repeatably and with high fidelity. The 2 Fr (0.66 mm) sensor can be implanted in the epidural or subdural space for measurement of intracranial pressure. Telemeters are available with single 25cm catheters (TRM54P25), dual catheters (TRM54PP2509) or in combination with a biopotential channel (TRM54PB25).

Publications:

• Thakkar, P. et al. Hypertensive Response to Ischemic Stroke in the Normotensive Wistar Rat: Mechanisms and Therapeutic Relevance. Stroke 50, 2522–2530 (2019).
• Kawoos, U et al. Protective Effect of N-Acetylcysteine Amide on Blast-Induced Increase in Intracranial Pressure in Rats. Frontiers in Neurology, 8, 219 (2017)

Epilepsy

Monitoring pathophysiological activity, such as epileptic seizure, in vivo has traditionally been challenging due to the spontaneous nature of the condition. Kaha Sciences’ innovative use of wireless power technology has removed the compromise of battery-life to allow users to record continuously at high sampling rate (2kHz) over long-term experiments. Our reusable rat biopotential telemeters give users the option to record a single EEG channel (TR50B) or combine EEG and nuchal EMG recordings (TR50BB), while our mouse telemeters (MT10B) allow the recording of EEG along with activity. The ability to record continuously ensures that more data is captured and fewer seizure events are missed.

Publications:

• Hill, A. C., et al. Correction of medication nonadherence results in better seizure outcomes than dose escalation in a novel preclinical epilepsy model of adherence. Epilepsia 60 (3), 475-484 (2019).
• Read, M. I., et al. Atenolol offers better protection than clonidine against cardiac injury in kainic acid‐induced status epilepticus. British Journal of Pharmacology 172 (19), 4626-4638 (2016).

Sleep and Circadian Rhythm

The ability to capture data in real time, 24/7 is invaluable in studying normal physiological rhythms over long experimental time courses. Using the Kaha Sciences rat (TR50B and TR50BB) and mouse (MT10B) biopotential telemeters it’s possible to record EEG or EMG and identify different stages in the sleep/wake cycle. Alternatively, users can benefit from the full range of Kaha telemeters to investigate ultradian or circadian rhythms in physiological parameters and how these might change in disease.

Publications:

• Emans, T. W. et al. Circadian Rhythm in Kidney Tissue Oxygenation in the Rat. Physiol. 8, (2017).

Tissue oxygen

The TR57Y tissue oxygen telemeter is the only device available on the market that can measure long-term tissue oxygen concentration from conscious rats, in real time. The telemeter uses a stable carbon paste electrode and can measure local ischemia and tissue metabolic activity in the brain or kidney. Combined with our wireless power technology researchers have been able to assess circadian variability in kidney tissue oxygen thanks to the ability to record 24/7.

Publications:

• Adamovich, Y. et al. Oxygen and Carbon Dioxide Rhythms Are Circadian Clock Controlled and Differentially Directed by Behavioral Signals. Cell Metab. 29, 1092-1103.e3 (2019).
• Russel, D, M. et al. A fully implantable telemetry system for the chronic monitoring of brain tissue oxygen in freely moving rats Journal Article. Journal of Neuroscience Methods, 204 (2), 242-248 (2012)

Sympathetic Nerve Activity (SNA)

The TRM56SP telemeters allow users to simultaneously record SNA and blood pressure to give an insight into the autonomic control of cardiovascular physiology. The input range of the SNA leads is ±60µV making it ideal for activity recording from fine, peripheral autonomic nerves studies in studies of stress, cardiovascular control and the development of hypertension.

Publications

• McBryde, F. D., Liu, B. H., Roloff, E. V., Kasparov, S. & Paton, J. F. R. Hypothalamic paraventricular nucleus neuronal nitric oxide synthase activity is a major determinant of renal sympathetic discharge in conscious Wistar rats. Physiol. 103, 419–428 (2018).

For more information please contact us.

In vivo physiology and neuroscience studies have been precluded by the lack of an effective and efficient means of collecting meaningful data from conscious experimental animals over long periods of time. The introduction of telemetry technologies has improved this; however, the duration of experiments continues to be constrained by battery life, either restricting the user on the amount or quality of data collected. The Kaha Sciences rat and mouse telemetry systems utilise wireless power technology to remove the dependency on battery power, allowing our customers to collect high frequency data without compromising on the duration of the experiment.

The restraint of animals, including tethering, for long-term physiological experiments increases stress which is likely to directly affect physiological parameters of interest, such as heart rate¹. The implantation of telemetry devices has provided an elegant solution to these problems because, following recovery from a short surgical procedure, animals are able to behave naturally in their home-cage with no, or reduced, handling¹. Telemeter implants do, however, require power and this is most often achieved by the inclusion of a battery. Not only can this increase the size of the implant but relying on battery-life alone can restrict data collection time and reduce the fidelity of data by compromising on sampling rate.

The Kaha Sciences solution removes these limitations by using inductive wireless power, to power both rat² and mouse³ telemeters (Fig. 1). Our TR181 SmartPads (for rats) and MT110 tBases (for mice) generate a magnetic field from mains electrical power which passes safely through non-metallic rodent cages and tissue. The implant is positioned such that the magnetic field powers the telemeter in a freely moving rodent, allowing the freedom to collect high resolution (2kHz), physiologically accurate data in real time, 24 hours a day, 7 days a week.

Without the concern of limited power, the ability to record 24/7 at a high sampling rate has allowed our customers to publish studies on circadian variability in kidney oxygenation (TR57Y tissue oxygen telemeter)⁴, spontaneous arrhythmias in a rat model of complete atrioventricular block (TR50BB dual biopotential telemeter)⁵ as well as monitor unpredictable seizure events in a rat model of epilepsy (TR50B single biopotential telemeter)⁶.

This technology is just one example of Kaha Sciences innovative telemetry systems with uncompromising ability which allow our customers to get more data from their studies.

For more information please contact us.

1. Niemeyer, J. E. Telemetry for small animal physiology. Lab Anim. 45, 255–257 (2016).
2. Budgett, D. M. et al. Novel technology for the provision of power to implantable physiological devices. J. Appl. Physiol. 102, 1658–1663 (2007).
3. Russell, D. M., McCormick, D., Taberner, A. J., Malpas, S. C. & Budgett, D. M. A high bandwidth fully implantable mouse telemetry system for chronic ECG measurement. in 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society 7666–7669 (IEEE, 2011). doi:10.1109/IEMBS.2011.6091889
4. Emans, T. W., Janssen, B. J., Joles, J. A. & Krediet, C. T. P. Circadian Rhythm in Kidney Tissue Oxygenation in the Rat. Front. Physiol. 8, (2017).
5. Kim, N. K., Wolfson, D., Fernandez, N., Shin, M. & Cho, H. C. A rat model of complete atrioventricular block recapitulates clinical indices of bradycardia and provides a platform to test disease-modifying therapies. Sci. Rep. 9, 6930 (2019).
6. Hill, A. C., Thomson, K. E., Newell, T. G. & White, H. S. Correction of medication nonadherence results in better seizure outcomes than dose escalation in a novel preclinical epilepsy model of adherence. Epilepsia 60, 475–484 (2019).

When designing in vivo experiments biomedical researchers are mindful of the 3Rs¹ to improve animal welfare and ensure the appropriate quantity, quality and relevance of data collected from each animal. Applying the latest technologies Kaha Sciences have developed and improved the rat telemetry system with refinement and reduction in mind providing a solution that encompasses these important principles.

Rats are a social species and should ideally be housed with at least one cage-mate for the duration of studies².  Some telemetry technologies require single housing, despite the recognized detrimental effects on behaviour³ and the possible impact this may have on physiological data. Solutions including the introduction of an unimplanted cage-mate and the housing of two implanted rats together with alternating recording days are not always ideal.  Non-experimental cage-mates can increase the cost of experiments without directly contributing to the research outcome and alternate recording days decreases the quantity of data collected from each animal and continuity. The Kaha Sciences Cohousing feature allows simultaneous collection of continuous data from two (Fig 1.).  With this feature customers increase welfare while reducing animal use and husbandry costs.

The Kaha Cohousing feature can also support implantation of two telemeters in one rat (>350g). This provides the user with the ability to customise experimental protocols and record up to four signals in unique telemeter combinations.  This customisable capability has recently been published by Thakkar et al in which TRM54PP and TR57Y telemeters were implanted in a single rat to simultaneously record arterial blood pressure, intracranial pressure and brain tissue oxygen to investigate hypertensive responses to stroke in rats⁴.  This approach dramatically increases the value of each animal by reducing the number of animals required and introduces the ability to take a true “systems” approach to physiological research.

The Kaha Sciences Cohousing feature allows our customers to implement both refinement and reduction to their research activity, while also reducing time and cost.  This and other unique benefits of the Kaha Sciences telemetry solutions assists our customers to push the boundaries of biomedical research.

For more information please contact us.

1. https://www.nc3rs.org.uk/. The 3Rs.
2. THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,. DIRECTIVE 2010/63/EU.
3. Pinelli, C., Leri, F. & Turner, P. Long Term Physiologic and Behavioural Effects of Housing Density and Environmental Resource Provision for Adult Male and Female Sprague Dawley Rats. Animals 7, 44 (2017).
4. Thakkar, P. et al. Hypertensive Response to Ischemic Stroke in the Normotensive Wistar Rat: Mechanisms and Therapeutic Relevance. Stroke 50, 2522–2530 (2019).