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EP-4735899-A1 - METHOD OF STIMULATING A LIVING HUMAN OR ANIMAL CELL USING A CHARACTERISTIC SIGNAL OF THE CELL AND RELATED APPLIANCE

EP4735899A1EP 4735899 A1EP4735899 A1EP 4735899A1EP-4735899-A1

Abstract

This disclosure relates to analysis of biological patterns and more in detail a method of generating a characteristic signal of a living human or animal cell and a related device for implementing it, as well as a method of stimulating a living human or animal cell either in vivo or in vitro and a related appliance.

Inventors

  • VENTURA, CARLO

Assignees

  • Eldor Lab S.r.l.

Dates

Publication Date
20260506
Application Date
20250116

Claims (12)

  1. 1. A method of stimulating a living human or animal cell either in vivo or in vitro extracted from a human or animal body, comprising the following steps: generating a characteristic signal of the living human or animal cell; generating a mechanical stimulation or a modulated light stimulation by means of a piezo-electric or light actuator controlled according to data of the characteristic signal of said living human or animal cell, wherein said modulated light stimulation is generated by modulating with said characteristic signal an intensity of a light beam absorbable by said living human or animal cell; applying said mechanical or light stimulation to said living human or animal cell; wherein said characteristic signal is generated through the following operations: placing the extracted living cell into a test solution; sensing a vibration of a superficial portion of an external surface of said extracted living cell; generating a transduced time-varying signal corresponding to said sensed vibration; low-pass filtering values of said transduced time-varying signal in the frequency range below 20Hz, generating data of said characteristic signal as a low-pass filtered replica of the values of said transduced time-varying signal.
  2. 2. The method of claim 1, wherein said transduced signal is generated by: procuring and installing an atomic force microscope having a sensing tip; placing the sensing tip in contact with the external surface of the extracted living cell; generating said transduced signal as an electric signal representative of vibrations sensed by said sensing tip.
  3. 3. The method of claim 1, wherein said transduced signal is generated by: procuring and installing an illuminating laser configured to illuminate the external surface of the cell; procuring and installing an optical sensor configured to sense light scattered by the external surface of the cell; generating said transduced signal as an electric signal representative of intensity of light, received by the optical sensor, which has been scattered by said external surface.
  4. 4. The method according to one of the preceding claims, wherein said characteristic signal is generated as a low-pass filtered replica of values of said transduced signal in the frequency range below 10Hz, preferably below 8Hz.
  5. 5. An appliance for stimulating a living human or animal cell either in vivo or in vitro extracted from a human or animal body, comprising: a controlled piezo-electric or light actuator, configured to generate a mechanical or light stimulation to be applied to the living human or animal cell; a microprocessor unit, configured to receive data of a characteristic signal of said living human or animal cell generated according to the method of one of claims from 1 to 4, and configured to generate corresponding command signals for the piezo-electric or light actuator so as to cause the piezo-electric or light actuator to generate the mechanical or light stimulation corresponding to the data of the characteristic signal.
  6. 6. The appliance of claim 5, further comprising a non-volatile memory storing said data of the characteristic signal, wherein said microprocessor is configured to download said data of the characteristic signal from the non-volatile memory and to process the sata when the command signals for the piezo-electric or light actuator have to be generated.
  7. 7. The appliance of claim 5 or 6, further comprising a current modulator configured to be controlled by the microprocessor unit and to generate a waveform of a control voltage or control current corresponding to said data of the characteristic signal, wherein said current modulator is functionally coupled to control said controlled piezoelectric or light actuator with said control voltage or control current to cause the piezoelectric or light actuator to generate the mechanical or light stimulation corresponding to the data of the characteristic signal.
  8. 8. The appliance of claim 7, wherein: said actuator comprises a plurality of groups of LEDs supplied by a respective plurality of electric lines, the LEDs of each group being connected electrically in series among them and configured to be supplied through a corresponding electric line of said electric lines; the appliance further comprises a channel selector controlled by the microprocessor unit through a command signal and connected to the current modulator and said actuator, configured to receive from said current modulator a current and to supply selectively the groups of LEDs through said electric lines depending on said command signal generated by the microprocessor unit.
  9. 9. The appliance of claim 8, wherein each group of LEDs of said plurality of groups of LEDs of the actuator is allocated in a corresponding hexagonal irradiation zone of a Printed Circuit Board and comprises a plurality of LEDs electrically in series among them disposed along a perimeter and at a center of the corresponding hexagonal irradiation zone.
  10. 10. The appliance of claim 8, wherein each group of LEDs of said plurality of group of LEDs of the actuator is allocated in a FPCB (Flexible Printed Circuit Board) irradiation zone comprising a plurality of LEDs electrically in series, wherein the LEDs are spatially placed following an equilateral triangular pattern.
  11. 11. The appliance of claim 8 or 9, wherein said actuator is shaped as a wearable band that may be worn directly in contact with a skin of a user.
  12. 12. The appliance of claim 8 or 9, wherein said actuator is shaped in the form of a helmet/cup that may be worn directly in contact with the scalp, or said actuator is shaped in the form of a bite to be placed inside the mouth of a user in contact with the gingival mucosa and/or teeth of the user.

Description

METHOD OF STIMULATING A LIVING HUMAN OR ANIMAL CELL USING A CHARACTERISTIC SIGNAL OF THE CELL AND RELATED APPLIANCE TECHNICAL FIELD This disclosure relates to analysis of biological patterns and more in detail a method of stimulating a living human or animal cell either in vivo or in vitro extracted from a human or animal body using a characteristic signal of the cell, and a related appliance. BACKGROUND Increasing evidence show that biological patterns are fashioned not only by chemical, but even physical signaling, including mechanical waves, electric patterning and gradients, as well as electromagnetic radiations, which also include light [1]. Such physical energies are sensed and released by somatic and stem cells, and are currently gaining consideration as a part of a morphogenetic code underlying the causal relationship between the establishing of defined domains at the molecular level, the emergence of supramolecular structures, the timely unfolding of subcellular and cellular shapes, up to the appearance of the large-scale anatomy of tissue and organs and the entire individual specification. When thinking at ourselves as a part of the oscillatory nature of the Universe, we became aware that physical forces are essential in the orchestration of living organisms, as it is shown by: (i) the physical dynamics of molecular folding, (ii) the progressive deciphering of mechanical and electromagnetic patterning essential in the establishment of nano-architectonics using suprainteractions, and (iii) the biomolecular recognition and signal propagation afforded through dynamics of molecular synchronization and swarming [1]. At the physical level, all biological processes entail a form of vibration. By the aid of sophisticated devices and methods, including atomic force microscopy (AFM) [2-5], scanning tunneling microscopy (STM) [6,7], terahertz near-field microscopy (THz- NFM) [8], and hyperspectral imaging (HSI) [9-11] we are now dissecting and deciphering specific vibrational patterning at subcellular and cellular level. Thus, a single peptide molecule appears as helix-loop-helix repeats. These are intrinsically oscillatory domains, as the helices behave as a spring (oscillator), with the loops acting as inter-oscillator linkers. These springs are electrically polarized, including both the positively-charged amino groups (such as those in Lysine and Arginine), and the negatively-charged carboxyl groups (such as those in Aspartate and Glutamate), as well as the backbone dipole interactions in the formation of secondary and super- secondary protein structures. Therefore, the helices in a signaling molecule not only behave as mechanical oscillators, but acquire the state of an electromechanical actuator, with electro-mechanical interacting potential with other similar helix-loop-helix modules from a multitude of signaling players. As a result, the mechanical oscillation of such cell signaling actuators is also capable of generating an electric field, with radiation characteristics. Compounding the multi-level features of complexity ensuing from such view, a consistent number of signaling molecules are now found to unfold their vibrational features into the capability of absorbing and emitting light within defined domain spectra, therefore being deemed as “chromophores”. The list of such chromophore molecules is constantly increasing over time, now including flavins, flavoproteins and cytochromes [12-16], such as those responsible for the generation of reactive oxygen species (ROS) and nitric oxide [15,17- 19], which act as essential pleiotropic players in cellular dynamics. There is now mounting evidence that essential signaling paths in both somatic and stem cells are controlled by opsins, a group of cis-retinal dependent G protein-coupled receptors, encompassing members of the family of transient receptor potential cation channels (TRPs) [14,20,21]. TRPs encompass multiple superfamily members which are selectively operated by specific light wavelengths, playing a pivotal role in cellular decisions [22-26], as photoentrainment and cellular circadian rhythms [26]. Intriguingly, melanopsin (Opn4), a non-image-forming opsin, has been shown to afford a physiological role in the modulation of blood vessel function, particularly in the context of photoinduced vascular relaxation (photorelaxation) [27]. Opn4 is expressed in blood vessels. Force-tension myography provided evidence that vessels from Opn4 /_ mice lacked photorelaxation, which was also abrogated by an Opn4- specific inhibitor. The observed photorelaxation was wavelength- specific, and did not involve endothelial, nitric oxide-, carbon monoxide-, or cytochrome p450-derived vasoactive prostanoid signaling, but was associated with vascular hyperpolarization, and was also soluble guanylyl cyclase- and phosphodiesterase 6-dependent [27]. The presence of Opn4 in blood vessels has also been confirmed in pulmonary arterial smooth muscle cells and pulmonary a