Skip to Main Content
Skip Nav Destination

Stavrinidou, E. and Proctor, C. M., “Introduction,” in Introduction to Bioelectronics: Materials, Devices, and Applications, edited by E. Stavrinidou and C. M. Proctor (AIP Publishing, Melville, New York, 2022), pp. 1-1–1-16.

Bioelectronics is the field that involves the development of electronic interfaces with main objective to monitor or modulate biological processes. This introductory chapter provides background on electrical signalling in biology and gives a brief historical overview of the bioelectronics field. Then it focuses on bioelectronic technologies that are currently used in the clinic providing a historical perspective but also presenting the state of the art. Furthermore, current trends and future perspectives of the field are discussed. Finally, an overview of the chapters included in the book is given.

Bioelectronics, as the most general definition, is the field that interfaces electronics with biology. For example, a bioelectronic device can be used to probe a biological reaction. In this case, the biological process is inducing a change in the bioelectronic device, which then is translated to a readable output. In this way, a glucose biosensor can determine the glucose levels in the blood. A bioelectronic device can also be used to induce a biological process in a controlled manner. A pacemaker, for example, can stimulate and regulate heartbeat.

Bidirectional communication between electronics and biology can happen at many levels and can vary in complexity both from the biological and the technological perspectives. When discussing biology, we may refer to simple cell components, e.g., proteins and nucleotides, organelles, whole cells, tissues, organs, and even a complex organism. Electronics, on the other hand, can include electronic materials, passive components (e.g., electrodes), active components (e.g., transistors), and even complex devices and circuits.

The development of bioelectronic technologies is motivated by the need to probe and communicate with the biological world in order to understand better how it works and/or how to influence its function. Apart from scientific curiosity, one of the main driving forces of bioelectronics is the development of new therapies and new diagnostics to treat diseases, improve the quality of life of patients, and extend the duration of human life.

But how to establish communication between two worlds that are fundamentally so different? Electronic devices are typically rigid, their operation relies on electronic currents, and their active components are insulated from the environment in order to ensure high performance. In addition, the operation and physics of traditional electronic devices are generally well understood. On the other hand, biological components are soft, processes take place in an aqueous medium, and long-range communication is realized mainly with ionic currents or via chemical signaling. Biological processes are highly complex, and current biophysical models describe well only simplified functions. This book will explore emerging concepts, materials, and technologies that attempt to bridge the world of biology with electronics. In Secs. 1.2–1.5, we will provide some background on biological processes that involve electrical signaling, overview the historical timeline of bioelectronics, and present the current state-of-the art of technologies used in the clinic.

One of the most important and widely known electrical signals in biology is the neuronal action potential. The neurons are specialized cells in the brain that carry the fundamental bit of information. Although the action potential is often described as a current that travels along the neuron, it is purely ionic. The driving force is the membrane potential, the difference in ionic concentration between intracellular and extracellular environment. The ionic current is generated when specialized proteins on the cell membrane, the ion channels, are activated, enabling exchange between cations and anions inside and outside of the cell. The action potential travels along the neuron without losing its amplitude because the signal is regenerated throughout the axon by the activation of adjacent ion channels. When the signal reaches the end of the axon, it triggers the release of neurotransmitters that are chemical messengers able to diffuse and reach the adjacent neuron, inducing an action potential. The action potential is triggered only if the transmembrane potential reaches a threshold and, therefore, is also called an “all or nothing event.” Communication between neurons occurs across a small gap known as the synapse, where nerve impulses are relayed electrically or chemically from the axon of a presynaptic (sending) neuron to the dendrite of a postsynaptic (receiving) neuron, Fig. 1.1.

FIG. 1.1

Chemical synapse. Neurotransmitters released from the presynaptic neuron bind to the receptors of the postsynaptic neuron, inducing the generation of the action potential.

FIG. 1.1

Chemical synapse. Neurotransmitters released from the presynaptic neuron bind to the receptors of the postsynaptic neuron, inducing the generation of the action potential.

Close modal

Motor neurons can also form synapses at neuromuscular junctions with muscle fibers and, in this way, control their contractions. The neurotransmitters that are released from the neuron attach to the cell membrane of the muscle fiber, causing membrane depolarization, and after a cascade of reactions, there is contraction of the fiber.

The heart function is controlled by electrical signals as well. However, the cardiomyocyte contraction is not controlled directly from neurons but from specialized cells, the cardiac pacemaker's cells. These cells depolarize spontaneously and through gap junctions initiate the depolarization of adjacent cells. The gap junctions are specialized connections between the intracellular space of two cells, enabling the electrical signal to travel from one cell to the other.

There are examples where electrons play a vital role in biological reactions as well in the form of electrochemical redox reactions. However, these reactions are usually very localized, and electrons are exchanged within molecules in proximity. An example is the generation of reactive oxygen species (ROS) in oxidative stress.

An investigation of the muscle movement in animals led to the beginning of bioelectronics. In Italy, at the end of the 18th century, a man called Luigi Galvani was interested in physiology (Piccolino, 1997). Galvani studied medicine and was working with his father-in-law, a professor in Physiology focusing on anatomical studies. He was living in Bologna, which was a strong and diverse scientific hub of that era, and was a strong believer that animal research is essential for understanding human physiology and, therefore, performed many experiments on animals (Heilbron, 1991). Although his main research interest was medicine, he became fascinated by electricity and the work of Benjamin Franklin that took place decades before. At that time, from the work of Haller and others, it was known that electricity could stimulate the muscle, but it was not known whether electricity was responsible for the movement. Galvani started his investigations having Haller's work as a reference point. Having a curious mind, he wanted to test the validity of the then current theories, so he began his work on muscle movement. One of the most famous experiments by Galvani was the one performed on frogs in 1780. Galvani had a detached leg of a frog on a brass hook. When he inserted his steal scalpel, he touched the exposed sciatic nerve and then the frog leg twitched. Galvani brought to the forefront the notion of neuroelectricity, which was described as the electrical fluid in the muscle that is responsible for movement. He termed the electrical fluid “animal electricity,” a type of electricity that was intrinsic to animals and was the driving force for the muscle movement. Now, at the same time, another Italian scientist, Alessandro Volta, heard about Galvani's experiments and animal electricity (Geddes and Hoff, 1971; and Bernardi, 2001). He was not completely convinced with the theory on animal electricity and started experimenting himself. His experiments with the electrodes of various materials led to the invention of the first battery, the so-called voltaic pile in early 1800. The voltaic pile consisted of zinc and copper disks that have different work functions and in between an electrolyte. Voltas's work demonstrated that what Galvani did was to electrically stimulate the sciatic nerve as the brass and steal that he inserted in the tissue resulted in a voltage difference. Volta also used his battery to stimulate various tissues, including the ear. Using himself as a guinea pig, he connected the battery leads on his ears, and as soon as the circuit closed, he felt a shock and then heard noises. This was possibly the first time that electricity was related to hearing. However, Volta was frightened from this experience and never repeated it. What Volta offered, though, was the possibility to produce electricity without the use of static electricity and, therefore, simplify the experimentation for studying the effect of electricity in biology. Electrical stimulation of the ear was not so much investigated or at least not reported until the next century. In the 1930s, Stevens started working on the electrical stimulation of hearing, which later led to the development of the cochlear implant, which will be discussed in Sec. 1.4.2 (Stevens, 1937). Galvani is considered the father of Bioelectronics, the one connecting electricity with nerves and muscle movement. However, it was not until the 1940s and 1950s, in the work of Andrew Huxley and Alan Hodgkin, that the action potential was recorded for the first time and its origin was resolved (Hodgkin et al., 1952; Hodgkin and Huxley, 1952a, 1952b; and Schwiening, 2012). Using an electrode within a glass micropipette, they recorded the intracellular action potential of the giant axon of the Atlantic Squid (1939). Because of the Second World War, they had to pause their work. In 1949, they continued their collaboration and developed the voltage clamp, which enabled them to record the ionic currents across the membrane of the axon. Furthermore, they developed a mathematical model that describes the action potential and its propagation as a function of the lipid membrane capacitance, currents from sodium and potassium voltage-gated ion channels, and current from leak channels. Their discovery earned them the Nobel prize in Physiology and Medicine in 1963.

The application of bioelectronics in medicine is one of the most innovative and exciting directions in healthcare today. Bioelectronics is used to advance diagnosis and care for people suffering from an ever-growing range of challenging diseases and conditions (Fig. 1.2). From treatment of heart problems (arrhythmias) to deafness to bladder control to chronic pain, bioelectronic interventions have reshaped the lives of millions of patients. The global market for bioelectronics in medicine already exceeds $22 billion and is projected to grow to more than $60 billion by 2030 (Tsao, 2019). Below, we present a brief synopsis of a selection of the most prominent clinical-grade bioelectronic technologies today.

FIG. 1.2

Schematic highlighting prominent applications for bioelectronic devices in healthcare.

FIG. 1.2

Schematic highlighting prominent applications for bioelectronic devices in healthcare.

Close modal

Over the centuries, there were examples of physicians or scientists who discovered a correlation between heartbeat and electric current, but it was not until the end of the 19th century, in the work of Aguste Desire Waller and Willem Einthoven, that the electrical activity of the heart was resolved with the use of the Lippman electrometer (Aquilina, 2006). Waller was the first to successfully record the electrocardiogram (ECG) in a clinical setting, but he did not realize the implications of his discovery in diagnosis and therapy. On the other hand, Eindhoven grasped the importance of ECG and developed the string galvanometer, which enabled a visualization of the ECG on a photographic plate. For his work on ECG and the string galvanometer, he was awarded the Nobel in Physiology and Medicine in 1924. Today, a 12-electrode system is used, which amplifies the signal, and it was developed in 1942 by E. Goldberg.

The use of electric current to modulate the heartbeat was shown in the 1930s independently by Doctors Mark Lidwell and Albert Hyman (Aquilina, 2006; and Sutton et al., 2007). Hyman's electromechanical device could stimulate the heart through a bipolar needle electrode that could be inserted through the skin. His method, though, was not widely accepted but rather seen with skepticism as it was interfering with natural processes. Furthermore, engineering problems rendered the method ineffective. In the 1950s, there were several examples of bulky stimulators with external controllers based on vacuum tubes and requirement for connection with a power outlet. The first truly portable stimulator was a battery-operated wearable pacemaker that was invented by Earl E Bakken, co-founder of Medtronic Inc., one of, if not the most, successful biomedical device companies that is still active (https://www.medtronic.com/; and Spencer, 2001). It required a 9.4 V mercury battery, and the stimulation was modulated via a transistor circuit. Surgeon C. Walton Lillehei applied the device on a patient only after 4 weeks of experimentation. This is something that would be impossible today due to strict regulations for translation of devices to the clinic. The first fully implantable pacemaker was designed by Swedish surgeon Ake Senning and physician and inventor Rune Elmqvist (European Perspectives, 2007). Senning and Elmqvist wanted to minimize the risk of infection caused by the open route between electrodes and controllers in portable or wearable devices. Therefore, they designed a device that included the battery and the circuit within a box that could be placed in the abdominal wall. The battery could be recharged via induction with external coupling. The first fully implantable pacemaker was implanted in Arne Lasson, but it operated only for a few hours, while the second one lasted for about a week. Arne Lasson went on to receive 26 pacemakers during his life and died in 2001 at the age of 86 due to a non-heart-related cause.

Following decades of technological development, pacemakers have evolved from being the last reserve of a surgeon to being a cornerstone of modern healthcare. Today, pacemakers are small enough to be implanted via a small catheter and can be designed to stimulate different chambers of the heart (Fig. 1.3). Pacemakers have also been combined with implantable defibrillators for patients at high risk of cardiac arrest. The defibrillator sends a larger electrical stimulus to the heart that essentially “reboots” it to get it pumping again. Modern pacemakers are typically programmed to adjust the stimulation in response to the patient's needs, providing stimulus only when needed. If the device senses that the heart has missed a beat or is beating too slowly, it will intervene to restore a steady rhythm. Pacemakers may also incorporate sensors that monitor movement and/or breathing rates to better match stimulation patterns to activity.

FIG. 1.3

Schematic showing key components of a standard implantable pacemaker system.

FIG. 1.3

Schematic showing key components of a standard implantable pacemaker system.

Close modal

The inventor of the cochlear implant was William F. House, an American physician with a specialty in otology (https://www.nytimes.com/2012/12/16/health/dr-william-f-house-inventor-of-cochlear-implant-dies.html?_r = 0). He was very innovative, and despite the criticism he received by his peers, he stayed true to his beliefs and proceeded to the development of the cochlear implant. He performed the first implantation in 1961, but it was rejected by the patient. In 1969, the implantation was successful, and his design became commercial in 1972. House's cochlear implant was a single channel stimulator and was, therefore, not effective for detecting speech. This would require the stimulation of various locations in the inner ear in order for the patient to differentiate between low and mid-high frequencies. During the same period in Austria, electrical engineer Ingeborg J. Hochmair–Desoyer, together with physician Erwin Hochmair, developed the first multichannel cochlear implant at TU Vienna (http://cochlearimplantonline.com/site/journey-to-developing-med-els-cochlear-implant-interview-with-dr-ingeborg-and-professor-erwin-hochmair-founders-of-med-el/). Although their design consisted of eight stimulating electrodes instead of one, it was still questioned if it could achieve speech recognition considering the 20 000 hair cells of the inner ear. But surprisingly it worked, and the patient could detect speech. According to Hochmair–Desoyer, this could have been a result of the plasticity of the brain that learns to adapt. In Australia, in parallel with the Austrian team, Graeme Clark invented a 22 multichannel cochlear implant (https://graemeclarkfoundation.org/about-graeme-clark/). Clark also faced criticism for his ambition but never quit, as he truly believed that it was the only way to restore hearing. Clark's invention was inspired by his deaf father. In 1978, Clark performed the first surgery, and together with his team, they were able to enable speech recognition to deaf people. Clark founded the Cochlear Limited to commercialize and make widely available his invention. Deafness is not a life-threatening condition, but deaf people can face a lot of struggles during their life. The cochlear implant is, therefore, an example of a bioelectronic device that can significantly improve the quality of life for patients.

Today, cochlear implants are regularly implanted in deaf and severely hearing-impaired patients starting within the first year of life (Fig. 1.4). The implants that have up to 22 electrodes are designed to last a lifetime, though failures occasionally do occur, thereby necessitating a replacement surgery. Remarkably, cochlear implants enable many patients to have near 100% speech recognition when combined with lip reading in quiet environments (Eisenberg et al., 2006). Nonetheless, even the most modern cochlear implants do not restore normal hearing. More complex sounds and noises, including music, are not well conveyed, and discerning speech in noisy environments remains particularly challenging for cochlear patients. Despite these limitations, the cochlear implant is widely regarded as one of the most successful bioelectronic technologies.

FIG. 1.4

Schematic showing key components of a standard cochlear implant system.

FIG. 1.4

Schematic showing key components of a standard cochlear implant system.

Close modal

Electrical stimulation of the brain was used from the beginning of stereotactic neurosurgery (https://www.ninds.nih.gov/About-NINDS/Impact/NINDS-Contributions-Approved-Therapies/DBS). In 1947, neurologist Spiegel and neurosurgeon Wycis developed a stereotactic apparatus for brain surgery, which enabled them to target in a precise manner different brain areas (Spiegel et al., 1947). Initially, electrical stimulation was used to identify the area of the brain that would undergo lesioning. However, as early as 1952, it was proposed by Delgado and co-workers that an implantable recording and stimulation device can be therapeutic for psychotic patients (Delgado et al., 1952). Indeed, electrical stimulation improved the condition of psychotic patients or ones with behavioral disorders as it was reported in the following years (https://www.ninds.nih.gov/About-NINDS/Impact/NINDS-Contributions-Approved-Therapies/DBS). In the early years of deep brain stimulation (DBS) though, there were many controversial studies that raised ethical concerns (Baumeister, 2000). In the meantime, it was observed by several groups that high frequency ( f > 50 Hz) stimulation could stop the tremor mimicking the therapeutic effect of brain lesioning, while many other studies focused on the treatment of chronic pain, epilepsy, and movement disorders. Initially, surgeons used modified cardiac pacemakers as neurostimulators to enable stimulation at higher frequencies (Gardner, 2013). Because of the interest and promising results, Medtronics developed a neurostimulator device in 1968, and the term DBS was trademarked in 1975. In the late 1980s and early 1990s, the seminal work of Benabid et al. (1987, 1991), Siegfried, and Lippitz groups (Siegfried and Lippitz, 1994) demonstrated that DBS can be used as a treatment for essential tremor in Parkinsonian patients (Sironi, 2011). In 1997, DBS received FDA approval for the treatment of severe tremor in patients suffering from essential tremor or Parkinson's disease. In 2003, FDA allowed the use of DBS for the treatment of dystonia under the Humanitarian Device Exemption, while in 2009, the use of DBS for treating obsessive-compulsive disorder (OCD) was approved. DBS is safer than previous practices, which relied on lesional procedures, as it is not a permanent intervention, and it can change the brain activity in a controlled manner (Benabid, 2007; Kringelbach et al., 2007; and Sironi, 2011). Despite its use for treating several disorders, the exact mechanism has not yet been fully understood and is a subject of active research. Modern DBS systems use integrated sensors, most typically, electrophysiology recording electrodes, to feed back to the stimulator in a closed loop system Fig. 1.5. The first closed loop system was approved by the FDA in 2013 for the treatment of drug-resistant epilepsy. Closed loop systems are also being tested clinically for essential tremor, Parkinson's disease, depression, and chronic pain. In addition, to provide better patient outcomes (e.g., a greater reduction in seizures), closed loop systems significantly reduce stimulation time, thereby lowering power consumption and extending battery lifespan (Parastarfeizabadi and Kouzani, 2017). It is widely anticipated that continued research and development into biomarkers and feedback algorithms will further improve the efficacy of DBS therapies in the coming decades.

FIG. 1.5

Schematic showing key components of a standard deep brain stimulation system.

FIG. 1.5

Schematic showing key components of a standard deep brain stimulation system.

Close modal

Leland C Clark, an American biochemist, is considered the father of biosensors. He invented the Clark electrode, an amperometric sensor for detection of oxygen based on the current that is generated through oxygen reduction on an electrode surface (Wang, 2001; and Turner, 2013). He soon realized that the concept can be used for the detection of various analytes with the use of oxidoreductase enzymes. Together with Lyons, they invented the glucose enzymatic biosensor in 1962 by modifying the oxygen electrode with glucose oxidase (Wang, 2001). Their invention of glucose biosensors practically opened the field of biosensing for medical diagnosis. Although the glucose electrochemical biosensor was invented in the 1960s, it was not until the 1990s that it became obvious to the medical field that people suffering from diabetes had to monitor and control their glucose levels daily (Newman and Turner, 2005). The first generation of devices relied on the detection of hydrogen peroxide and the use of a platinum electrode as the catalyst. The main limitations of these devices are the interference from other species, which can also be oxidized at the electrode, and their oxygen dependence. To minimize the interference, a semipermeable or charged membrane is used, which allows only glucose to diffuse to the electrode. The second generation of electrochemical enzymatic biosensors replaced oxygen with another electron acceptor, an artificial mediator molecule, usually ferrocene or ferrocyanide. The enzyme is reoxidized by the mediator, while the oxidized mediator transfers the electron to the electrode. The first commercially available glucometer was a pen style device by Medisense Inc. in 1987 (Newman and Turner, 2005). It relies on disposable enzyme electrode strips that use mediators and are fabricated with screen printing on a plastic substrate. A small blood drop from the finger is placed on the strip, which is then connected to the glucometer, providing a readout of the glucose concentration in less than 1 min.

Many commercially available glucose sensors are now able to continuously monitor glucose levels with data transmitted wirelessly at regular intervals. Such sensors measure interstitial glucose levels, which is the glucose found in the fluid between the cells. This is largely done using enzymatic glucose sensors that react with glucose molecules in the interstitial fluid to generate an electric current that is proportional to the glucose concentration. Fluorescence-based optical sensors that are implanted subcutaneously have also emerged as a promising alternative to enzymatic sensors particularly due to their extended lifetime compared with enzymatic sensors (10 vs 90 days). As shown in Fig. 1.6, continuous glucose monitors are now used to provide real-time feedback to insulin pumps, which then autonomously inject insulin as needed to maintain blood sugar levels within the target range. Current commercial systems are considered a hybrid closed loop as meal-time boluses are still programmed manually. Nonetheless, many diabetes patients report that this semi-automated blood sugar control has been transformational, significantly improving the quality of life.

FIG. 1.6

Schematic showing key components of a closed loop glucose monitoring and insulin delivery system.

FIG. 1.6

Schematic showing key components of a closed loop glucose monitoring and insulin delivery system.

Close modal

As described above, the field of bioelectronics has come a long way since Galvani's first experiments. Bioelectronic technologies are now an essential part of modern healthcare, and the future potential is boundless. A look at the ongoing clinical and pre-clinical research suggests that the field is evolving faster than ever before. In recent years, clinical bioelectronic interventions have enabled paralyzed patients to walk again (Rowald et al., 2022), speech to be decoded from brain recordings (Anumanchipalli et al., 2019), mind-controlled prosthetic limbs with sensory feedback (Raspopovic et al., 2021), and restoration of partial vision for the blind (Bloch et al., 2019). Current research on the clinical front is particularly focused on expanding applications, reducing invasiveness, identifying disease biomarkers, and expanding the use of closed loop control systems. Meanwhile, an even larger body of pre-clinical research is yielding vast improvements in bioelectronic materials, devices, and systems for interfacing with biology. These developments are enabling new capacities such as implants that mimic tissue to mitigate foreign body reactions, controlled drug delivery in the brain, minimally invasive implants, and wearable devices for real-time monitoring of a large range of biochemicals and disease biomarkers as well as interventions for wound healing and tissue regeneration. Bioelectronic technologies are also being adapted for highly sensitive in vitro diagnostics and drug development platforms. Efforts are increasingly expanding beyond the realm of healthcare to create new tools that underpin basic research including applications in plant science and agriculture. Such work promises to unveil yet more potential for bioelectronic interventions while also expanding our understanding of the life around us.

The aim of this book is to introduce key concepts underlying emerging technologies in the field of bioelectronics. The text is not meant to serve as an exhaustive review of every reported bioelectronic material, device, system, or application. Rather, we aim to present readers with an overview of core ideas, challenges, and trends in the most active areas of research and development. An effort is made to present concepts in an approachable manner suitable for the diversity of technical expertise in this inherently interdisciplinary field.

The subsequent chapters are divided into three sections. The first section describes the biological response to bioelectronic implants with an emphasis on biocompatibility and the foreign body response, an essential consideration for all bioelectronic applications. Section II presents the fundamentals of the four primary classes of bioelectronic devices. The first of these chapters, Chap. 3, focuses on passive electrodes, which have, to date, been the dominant bio-interfacing devices in both clinical and research sectors. Chapter 4 presents the fundamentals of transistor technologies in bioelectronics, which are particularly noteworthy for their high amplification and sensitivity for the monitoring of biosignals. In Chaps. 5 and 6, the focus shifts from technologies for electrical sensing and stimulation to chemical sensing and delivery. Chapter 5 overviews bioelectronic approaches to biochemical sensing, in other words converting a chemical signal to an electrical output. Chapter 6 explores the reverse process: converting an electrical input into a chemical output, a process broadly referred to as electronically controlled drug delivery.

Section III provides an overview of prominent bioelectronic application areas that have been the focus of extensive technological research and development in recent years. The chapters in this section each focus on a different application area providing background on related challenges and developments as well as an explanation of the basic biological and engineering principles. Chapters 7 and 8 focus on electrophysiology recordings in the nervous system and the principles of electrical stimulation of nerve tissue, respectively. In Chaps. 9–12, other developing application areas for bioelectronics are discussed, including in vitro systems, tissue engineering, retinal prothesis, and interfaces with plants.

Anumanchipalli
,
G. K.
,
Chartier
,
J.
, and
Chang
,
E. F.
, “
Speech synthesis from neural decoding of spoken sentences
,”
Nature
568
(
7753
),
493
498
(
2019
).
Aquilina
,
O.
, “
A brief history of cardiac pacing
,”
Images Paediatr. Cardiol.
8
(
2
),
17
81
(
2006
).
Baumeister
,
A.
, “
The tulane electrical brain stimulation program: A historical case study in medical ethics
,”
J. Hist. Neurosci.
9
(
3
),
262
278
(
2000
).
Benabid
,
A. L.
, “
What the future holds for deep brain stimulation
,”
Expert Rev. Med. Devices
4
(
6
),
895
903
(
2007
).
Benabid
,
A. L.
,
Pollak
,
P.
,
Hoffmann
,
D.
,
Gervason
,
C.
,
Hommel
,
M.
,
Perret
,
J. E.
,
de Rougemont
,
J.
, and
Gao
,
D. M.
, “
Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus
,”
Lancet
337
(
8738
),
403
406
(
1991
).
Benabid
,
A. L.
,
Pollak
,
P.
,
Louveau
,
A.
,
Henry
,
S.
, and
de Rougemont
,
J.
, “
Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease
,”
Stereotact. Funct. Neurosurg.
50
,
344
346
(
1987
).
Bernardi
,
W.
, “
La controverse sur l’électricité animale dans l’Italie du XVIIIe siècle: Galvani, Volta et… d’autres/The controversy over animal electricity in 18th-century Italy: Galvani, Volta and… others
,”
Rev. Hist. Sci. Paris
54
(
1
),
53
70
(
2001
).
Bloch
,
E.
,
Luo
,
Y.
, and
da Cruz
,
L.
, “
Advances in retinal prosthesis systems
,”
Ther. Adv. Ophthalmol.
11
,
251584141881750
(
2019
).
Delgado
,
J. M. R.
,
Hamlin
,
H.
, and
Chapman
,
W. P.
, “
Technique of intracranial electrode implacement for recording and stimulation and its possible therapeutic value in psychotic patients
,”
Stereotact. Funct. Neurosurg.
12
,
315
319
(
1952
).
Eisenberg
,
L. S.
,
Johnson
,
K. C.
,
Martinez
,
A. S.
,
Cokely
,
C. G.
,
Tobey
,
E. A.
,
Quittner
,
A. L.
,
Fink
,
N. E.
,
Wang
,
N.-Y.
, and
Niparko
,
J. K.
, “
Speech recognition at 1-year follow-up in the childhood development after cochlear implantation study: Methods and preliminary findings
,”
Audiol. Neurotol.
11
(
4
),
259
268
(
2006
).
European Perspectives
,
Circulation
115
(
22
),
f109
f114
(
2007
).
Gardner
,
J.
, “
A history of deep brain stimulation: Technological innovation and the role of clinical assessment tools
,”
Soc. Stud. Sci.
43
(
5
),
707
728
(
2013
).
Geddes
,
L. A.
and
Hoff
,
H. E.
, “
The discovery of bioelectricity and current electricity the Galvani-Volta controversy
,”
IEEE Spectr.
8
(
12
),
38
46
(
1971
).
Heilbron
,
J. L.
, “
The contributions of Bologna to galvanism
,”
Hist. Stud. Phys. Biol. Sci.
22
(
1
),
57
85
(
1991
).
Hodgkin
,
A. L.
and
Huxley
,
A. F.
, “
A quantitative description of membrane current and its application to conduction and excitation in nerve
,”
J. Physiol.
117
(
4
),
500
544
(
1952a
).
Hodgkin
,
A. L.
and
Huxley
,
A. F.
, “
The components of membrane conductance in the giant axon of Loligo
,”
J. Physiol.
116
,
473
496
(
1952b
).
Hodgkin
,
A. L.
,
Huxley
,
A. F.
, and
Katz
,
B.
, “
Measurement of current-voltage relations in the membrane of the giant axon of loligo
,”
J. Physiol.
116
(
4
),
424
448
(
1952
).
Kringelbach
,
M. L.
,
Jenkinson
,
N.
,
Owen
,
S. L. F.
, and
Aziz
,
T. Z.
, “
Translational principles of deep brain stimulation
,”
Nat. Rev. Neurosci.
8
(
8
),
623
635
(
2007
).
Newman
,
J. D.
and
Turner
,
A. P. F.
, “
Home blood glucose biosensors: A commercial perspective
,”
Biosens. Bioelectron.
20
(
12
),
2435
2453
(
2005
).
Parastarfeizabadi
,
M.
and
Kouzani
,
A. Z.
, “
Advances in closed-loop deep brain stimulation devices
,”
J. NeuroEng. Rehabil.
14
,
79
(
2017
).
Piccolino
,
M.
, “
Luigi Galvani and animal electricity: Two centuries after the foundation of electrophysiology
,”
Trends Neurosci.
20
(
10
),
443
448
(
1997
).
Raspopovic
,
S.
,
Valle
,
G.
, and
Petrini
,
F. M.
, “
Sensory feedback for limb prostheses in amputees
,”
Nat. Mater.
20
(
7
),
925
939
(
2021
).
Rowald
,
A.
,
Komi
,
S.
,
Demesmaeker
,
R.
,
Baaklini
,
E.
,
Hernandez-Charpak
,
S. D.
,
Paoles
,
E.
,
Montanaro
,
H.
,
Cassara
,
A.
,
Becce
,
F.
,
Lloyd
,
B.
, et al
, “
Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis
,”
Nat. Med.
28
(
2
),
260
271
(
2022
).
Schwiening
,
C. J.
, “
A brief historical perspective: Hodgkin and Huxley: Classical perspectives
,”
J. Physiol.
590
(
11
),
2571
2575
(
2012
).
See https://graemeclarkfoundation.org/about-graeme-clark/ for a biography of Prof. Graeme Clark.
See https://www.medtronic.com/ for information about Medtronic company.
Siegfried
,
J.
and
Lippitz
,
B.
, “
Bilateral chronic electrostimulation of ventroposterolateral pallidum: A new therapeutic approach for alleviating all parkinsonian symptoms
,”
Neurosurgery
35
(
6
),
1126
1129
(
1994
); discussion 1129-30.
Sironi
,
V. A.
, “
Origin and evolution of deep brain stimulation
,”
Front. Integr. Neurosci.
5
(
42
),
1
(
2011
).
Spencer
 III,
W. H.
, “
Earl E. Bakken
,”
Clin. Cardiol.
24
(
5
),
422
423
(
2001
).
Spiegel
,
E. A.
,
Wycis
,
H. T.
,
Marks
,
M.
, and
Lee
,
A. J.
, “
Stereotaxic apparatus for operations on the human brain
,”
Science
106
,
349
350
(
1947
).
Stevens
,
S. S.
, “
On hearing by electrical stimulation
,”
J. Acoust. Soc. Am.
8
(
3
),
191
195
(
1937
).
Sutton
,
R.
,
Fisher
,
J. D.
,
Linde
,
C.
, and
Benditt
,
D. G.
, “
History of electrical therapy for the heart
,”
Eur. Hear. J. Suppl.
9
(
suppl_I
),
I3
I10
(
2007
).
Tsao
,
N.
, Bioelectronic Medicine 2019–2029, IDTechEx (
2019
).
Turner
,
A. P. F.
, “
Biosensors: Sense and sensibility
,”
Chem. Soc. Rev.
42
(
8
),
3184
(
2013
).
Wang
,
J.
, “
Glucose biosensors: 40 years of advances and challenges
,”
Electroanalysis
13
(
12
),
983
988
(
2001
).
Close Modal

or Create an Account

Close Modal
Close Modal