Bioelectronic control of chloride ions and concentration with Ag AgCl contacts Michael Levin Research Paper Summary

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What Was Observed? (Introduction)

  • Chloride ions (Cl−) play an important role in many physiological processes like brain function, muscle contraction, and metabolism.
  • Cl− is also involved in several diseases such as epilepsy, cancer, and birth defects.
  • The ability to control Cl− in biological systems could help in therapies for these diseases.
  • This paper demonstrates a bioelectronic device using Ag/AgCl contacts to precisely control the concentration of Cl− in solution.
  • The device uses the Ag/AgCl reaction to transfer Cl− between the contact and solution, providing a way to regulate [Cl−] in a controlled manner.

What is Bioelectronics?

  • Bioelectronics is the field where biological processes are connected with electronic devices.
  • It involves converting ionic signals (like Cl− in our body) into electronic signals that can be used for sensing and controlling processes.
  • This helps in medical applications like controlling brain activities or managing disease symptoms by manipulating ions.

How Does the Ag/AgCl Device Work?

  • The Ag/AgCl device uses a reversible reaction: Ag + Cl− ↔ AgCl + e−, which allows Cl− to move between the Ag/AgCl contact and the solution.
  • A negative voltage on the device forces Cl− to move from the contact into the solution, increasing [Cl−] in the solution.
  • A positive voltage causes Cl− to move back from the solution into the contact, reducing [Cl−] in the solution.
  • This process can control the Cl− concentration precisely, which is useful in biological systems.

What Was the Experiment Setup? (Method)

  • Researchers used a three-electrode system with Ag/AgCl wire as the working electrode, a glass Ag/AgCl electrode as the reference electrode, and a platinum wire as the counter electrode.
  • The system was used to monitor Cl− changes in a solution using a fluorescent dye (MQAE), which changes its brightness depending on the Cl− concentration.
  • The researchers applied different voltages to the Ag/AgCl contact to move Cl− ions and observed the resulting changes in Cl− concentration and the fluorescence of the dye.

What Did They Find? (Results)

  • The device could precisely control Cl− concentration in a solution by applying either negative or positive voltages to the Ag/AgCl contact.
  • Changes in Cl− concentration were measured with the fluorescent dye MQAE, which showed that the device could shift [Cl−] from 50 mM to 32 mM and from 0 mM to 48 mM.
  • These changes in Cl− concentration were comparable to the changes in body fluids and relevant for biological applications.
  • The device was also able to work in complex solutions like stem cell culture media, which contain other ions besides Cl−, without interference from those other ions.

Chloride Modulator Design

  • The researchers designed a chloride modulator that uses Ag/AgCl NPs (nanoparticles) to control the flow of Cl− between two chambers.
  • The modulator consists of two chambers: a reservoir chamber filled with Cl− and a target chamber where Cl− concentration is controlled.
  • Cl− moves between the two chambers through an anion exchange membrane (AEM), and the device can control the concentration of Cl− in the target chamber.
  • This modulator can also influence the membrane voltage (Vmem) of human pluripotent stem cells (hiPSCs) by controlling extracellular [Cl−].

How Did the Device Affect the Cells? (Results with Cells)

  • The researchers used the chloride modulator to study how changing [Cl−] affects the membrane voltage of hiPSCs.
  • When extracellular [Cl−] was increased, the membrane voltage (Vmem) of the cells became more hyperpolarized (higher Vmem). When [Cl−] was decreased, the cells became depolarized (lower Vmem).
  • The Vmem change was measured using a fluorescent reporter (ArcLight), which showed the changes in cell voltage as the Cl− concentration was manipulated.
  • Fluorescence images showed clear changes in Vmem, with the areas close to the activated electrodes showing higher or lower Vmem.
  • This experiment showed how the chloride modulator can affect cell function by controlling the extracellular [Cl−].

Conclusion

  • The Ag/AgCl device is a powerful tool for controlling Cl− concentration in solutions using electronic signals.
  • By controlling Cl−, the device can manipulate bioelectric signals in biological systems, such as altering the membrane voltage in stem cells.
  • This has significant implications for bioelectronics and bioelectronic therapies, which can be used to treat diseases or control biological processes by manipulating ion concentrations.

观察到了什么? (引言)

  • 氯离子 (Cl−) 在许多生理过程中发挥重要作用,如大脑功能、肌肉收缩和新陈代谢。
  • Cl− 还参与了癫痫、癌症和出生缺陷等多种疾病。
  • 能够控制 Cl− 在生物系统中的浓度可能有助于这些疾病的治疗。
  • 本文展示了一种生物电子设备,利用 Ag/AgCl 接触点通过电子方式精确控制溶液中的 Cl− 浓度。
  • 该设备利用 Ag/AgCl 反应将 Cl− 从接触点转移到溶液中,从而提供一种受控的方式来调节 [Cl−]。

什么是生物电子学?

  • 生物电子学是将生物过程与电子设备相连接的领域。
  • 它涉及将体内的离子信号(如 Cl−)转化为电子信号,这些电子信号可用于传感和控制过程。
  • 这有助于医学应用,如通过操控离子来控制大脑活动或管理疾病症状。

Ag/AgCl 设备是如何工作的?

  • Ag/AgCl 设备利用一个可逆反应:Ag + Cl− ↔ AgCl + e−,使 Cl− 在 Ag/AgCl 接触点与溶液之间移动。
  • 设备上施加负电压,使 Cl− 从接触点转移到溶液中,从而增加溶液中的 [Cl−]。
  • 施加正电压使 Cl− 从溶液中回到接触点,减少溶液中的 [Cl−]。
  • 这个过程可以精确地控制 Cl− 浓度,在生物系统中非常有用。

实验设置是怎样的? (方法)

  • 研究人员使用一个三电极系统,其中 Ag/AgCl 电线作为工作电极,玻璃 Ag/AgCl 作为参考电极,铂电极作为对电极。
  • 该系统用于使用荧光染料 MQAE 监测溶液中 Cl− 的变化,染料的亮度会随着 Cl− 浓度的变化而改变。
  • 研究人员对 Ag/AgCl 接触点施加不同的电压,移动 Cl− 离子并观察荧光染料的变化。

他们发现了什么? (结果)

  • 该设备可以通过对 Ag/AgCl 接触点施加负电压或正电压来精确控制溶液中的 Cl− 浓度。
  • 通过使用荧光染料 MQAE,研究人员证明该设备能够将 [Cl−] 从 50 mM 改变为 32 mM,将 [Cl−] 从 0 mM 改变为 48 mM。
  • 这些变化与体液中的 Cl− 浓度变化相当,具有生物学应用的相关性。
  • 该设备在复杂溶液中也能够工作,比如干细胞培养基,其中含有除 Cl− 之外的其他离子,而不会受到这些离子的干扰。

氯调节器设计

  • 研究人员设计了一个氯调节器,使用 Ag/AgCl NPs(纳米颗粒)来控制 Cl− 在两个腔室之间的流动。
  • 调节器由两个腔室组成:一个储液腔室,充满 Cl−,另一个目标腔室用于控制 [Cl−] 浓度。
  • Cl− 通过一个阴离子交换膜(AEM)在两个腔室之间移动,设备能够控制目标腔室中的 Cl− 浓度。
  • 这个调节器还能够通过控制细胞外 [Cl−] 来影响人类多能干细胞(hiPSCs)的膜电压(Vmem)。

设备如何影响细胞? (细胞结果)

  • 研究人员使用氯调节器研究了改变 [Cl−] 如何影响 hiPSCs 的膜电压(Vmem)。
  • 当细胞外 [Cl−] 增加时,细胞的膜电压(Vmem)变得更超极化(更高的 Vmem);当 [Cl−] 减少时,细胞变得去极化(更低的 Vmem)。
  • 膜电压变化通过荧光报告分子(ArcLight)测量,显示细胞电压随着 Cl− 浓度的变化而变化。
  • 荧光图像显示,膜电压的变化发生在接触电极附近,而非活跃区域没有显著变化。
  • 这个实验显示了氯调节器如何通过控制细胞外 [Cl−] 来影响细胞功能。

结论

  • Ag/AgCl 设备是一个强大的工具,可以通过电子信号控制溶液中 Cl− 浓度。
  • 通过控制 Cl−,该设备可以操控生物系统中的生物电信号,例如改变干细胞的膜电压。
  • 这对生物电子学和生物电子治疗具有重要意义,可以通过操控离子浓度来治疗疾病或控制生物过程。