CN107684433B - A device and method for simultaneously detecting multiple physiological parameter indexes of a wound surface - Google Patents
A device and method for simultaneously detecting multiple physiological parameter indexes of a wound surface Download PDFInfo
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Abstract
本发明公开了一种检测创面多种生理参数指标的装置,包括:反射式光电检测模块、对创面生理参数敏感的敏感薄膜、以及位于敏感薄膜和光电器件之间的透明隔离层薄膜;所述的反射式光电检测模块包括一个光电接收管、n个发光二极管LED和驱动电路构成。将与不同波长的LED一一对应的n种敏感薄膜按照反射光路一一对应的位置布局,复用了多个生理参数的光电检测,可以利用不同波长的光分时检测创面的多种生理参数,并实现原位在线的多种生理参数检测。
The invention discloses a device for detecting various physiological parameter indexes of a wound surface, comprising: a reflective photoelectric detection module, a sensitive film sensitive to the physiological parameters of the wound surface, and a transparent isolation layer film located between the sensitive film and a photoelectric device; The reflective photoelectric detection module consists of a photoreceiving tube, n light-emitting diodes (LEDs) and a driving circuit. The n kinds of sensitive films corresponding to LEDs of different wavelengths are laid out according to the positions corresponding to the reflected light path, and the photoelectric detection of multiple physiological parameters is multiplexed, so that various physiological parameters of the wound can be detected by using different wavelengths of light in time division , and realize in-situ online detection of various physiological parameters.
Description
技术领域technical field
本发明属于生物医学工程领域,具体涉及一种利用不同波长的光实现分时原位在线检测创面的多种生理参数的装置及方法。The invention belongs to the field of biomedical engineering, and in particular relates to a device and a method for realizing time-sharing and in-situ online detection of multiple physiological parameters of a wound by using light of different wavelengths.
背景技术Background technique
我国每年手术病人在6500万人左右,伤口处理的绷带技术应用非常普遍。对于手术病人,面临的一个重要问题是手术后的创口愈合问题。常用的是使用压应力状态的绷带和纱布缠绕包裹的方式,这种方法简单易行,但是一旦包裹伤口后,医生就无法实时原位的监控伤口的生长状态,也不能实时对炎症等进行治疗,而伤口愈合是一个较长的时间,在这个较长时间内伤口都得不到准确的观察和诊断,哪怕是皮肤表面的手术,皮肤愈合也在10-20天左右,这个期间如果出现伤口早期炎症或者其他问题,就不能及时治疗。例如,创面感染不仅会导致创面愈合延迟,严重时还会危及病人的生命。在临床诊断中,早期采用有创的黄金标准方法,虽然测量比较准确,但需要不断地揭开纱布来检测创面状态,这就造成的伤口的二次伤害并增加二次感染的风险,而且具有价格昂贵、耗时和不能连续测量等缺点。因此,采用对创面感染标志物(如PH)敏感的生物传感器来检测创面状况,具有重要的临床指导意义。There are about 65 million surgical patients in my country every year, and the application of bandage technology for wound treatment is very common. For surgical patients, an important problem faced is wound healing after surgery. The most commonly used method is to wrap the bandage and gauze in a state of compressive stress. This method is simple and easy, but once the wound is wrapped, the doctor cannot monitor the growth status of the wound in real time in situ, nor can it treat inflammation in real time. , and wound healing takes a long time, and the wound cannot be accurately observed and diagnosed during this long period of time. Even if it is an operation on the surface of the skin, the skin will heal in about 10-20 days. If a wound occurs during this period Early inflammation or other problems cannot be treated in time. For example, wound infection will not only lead to delayed wound healing, but also endanger the life of patients in severe cases. In clinical diagnosis, the invasive gold standard method is used in the early stage. Although the measurement is relatively accurate, it needs to constantly uncover the gauze to detect the wound state, which will cause secondary injury to the wound and increase the risk of secondary infection, and has Disadvantages such as high price, time-consuming and non-continuous measurement. Therefore, the use of biosensors sensitive to wound infection markers (such as PH) to detect wound conditions has important clinical guiding significance.
基于此,人们提出了电子绷带技术。本发明复用了多个生理参数的光电检测,可以利用不同波长的光分时检测多种生理参数,包括动脉血氧饱和度、PH值、乳酸含量等,实现一个微小装置原位在线检测创面多种生理参数的功能。Based on this, people have proposed electronic bandage technology. The invention multiplexes the photoelectric detection of multiple physiological parameters, and can use different wavelengths of light to detect multiple physiological parameters in time division, including arterial blood oxygen saturation, pH value, lactic acid content, etc., to realize in-situ online detection of wounds with a tiny device Function of various physiological parameters.
发明内容Contents of the invention
鉴于上述,本发明提出了一种同时检测创面多种生理参数指标的装置,通过该装置能够实现原位在线检测创面的多种生理参数,包括动脉血氧饱和度、PH、乳酸含量等。In view of the above, the present invention proposes a device for simultaneously detecting multiple physiological parameters of wounds, through which various physiological parameters of wounds can be detected online in situ, including arterial blood oxygen saturation, pH, lactic acid content, etc.
本发明的技术方案为:Technical scheme of the present invention is:
一种同时检测创面多种生理参数指标的装置,其特征在于,包括:A device for simultaneously detecting multiple physiological parameter indexes of a wound, characterized in that it includes:
至少包括一个光电接收管、n个不同波长的发光二极管LED以及控制所述发光二极管LED的驱动电路的反射式光电检测模块;It includes at least one photoreceiving tube, n light-emitting diodes LEDs with different wavelengths, and a reflective photoelectric detection module that controls the driving circuit of the light-emitting diodes LED;
对创面生理参数敏感的敏感薄膜;以及,Sensitive films sensitive to physiological parameters of the wound; and,
位于所述敏感薄膜和所述反射式光电检测模块之间的透明隔离层薄膜。A transparent isolation layer film located between the sensitive film and the reflective photoelectric detection module.
工作原理为:n个发光二极管LED分时发射不同波长的激光信号,光信号通过透明隔离层薄膜照射于敏感薄膜表面,敏感薄膜由于生理参数变化,导致变色,在固定波长光下对于某创面生理参数的不同浓度具有不同的吸光度,并反射出不同波长的激光,反射光通过透明隔离层薄膜,进入光电接收管,光电接收管接收到光信号后产生光电流或电压,通过计算光电流或电压大小获得不同波长的光信号强度,从而获得该生理参数的大小变化。The working principle is: n light-emitting diodes emit laser signals of different wavelengths in time, and the light signals are irradiated on the surface of the sensitive film through the transparent isolation layer film. The sensitive film changes color due to changes in physiological parameters. Different concentrations of parameters have different absorbance, and reflect different wavelengths of laser light. The reflected light passes through the transparent isolation layer film and enters the photoelectric receiving tube. The photoelectric receiving tube generates photocurrent or voltage after receiving the optical signal. By calculating the photocurrent or voltage The magnitude obtains the intensity of the light signal at different wavelengths, thereby obtaining the magnitude change of this physiological parameter.
作为优选,所述的透明隔离层薄膜为透光率大于70%、且具有生物兼容性的透明薄膜。进一步优选,所述的透明隔离层薄膜为聚二甲基硅氧烷PDMS或聚乳酸PLA。该透明隔离层薄膜防止创面液腐蚀反射式光电检测模块,同时具有透气效果。Preferably, the transparent barrier film is a transparent film with a light transmittance greater than 70% and biocompatibility. Further preferably, the transparent barrier film is polydimethylsiloxane PDMS or polylactic acid PLA. The transparent isolation layer film prevents the wound surface fluid from corroding the reflective photoelectric detection module, and has a breathable effect at the same time.
作为优选,所述的隔离层薄膜的厚度为90~110μm。Preferably, the thickness of the isolation layer film is 90-110 μm.
作为优选,所述的敏感薄膜旋涂于透明隔离层薄膜上,工作时敏感薄膜接触创面,实现对创面生理参数的传感。Preferably, the sensitive film is spin-coated on the transparent isolation layer film, and the sensitive film contacts the wound surface during operation to realize the sensing of physiological parameters of the wound surface.
作为优选,所述的敏感薄膜的厚度为1μm~30μm。Preferably, the thickness of the sensitive thin film is 1 μm-30 μm.
作为优选,所述的敏感薄膜为PH敏感薄膜、葡萄糖敏感薄膜、乳酸敏感薄膜、氯离子敏感薄膜或金属离子敏感薄膜。Preferably, the sensitive film is pH sensitive film, glucose sensitive film, lactic acid sensitive film, chloride ion sensitive film or metal ion sensitive film.
作为优选,所述装置包括与不同波长的发光二极管LED一一对应的n种敏感薄膜,每种敏感薄膜将与其对应的发光二极管LED发射的光反射至光电接收管。与敏感薄膜对应的发光二极管LED是通过紫外-可见光分光光度计对敏感薄膜进行吸光度测试确定的,该发光二极管LED光照下,敏感薄膜的吸光度分辨率最高。这样能够快速准确地同时检测创面多种生理参数。Preferably, the device includes n kinds of sensitive thin films corresponding to light-emitting diodes LEDs with different wavelengths one-to-one, and each sensitive thin film reflects the light emitted by its corresponding light-emitting diode LED to the photoelectric receiving tube. The light-emitting diode (LED) corresponding to the sensitive film is determined by performing an absorbance test on the sensitive film with an ultraviolet-visible spectrophotometer, and the absorbance resolution of the sensitive film is the highest under the light of the light-emitting diode (LED). In this way, multiple physiological parameters of the wound surface can be detected quickly and accurately at the same time.
一种检测创面多种生理参数指标的方法,利用上述装置,复用多个生理参数的光电检测,利用不同波长的光分时检测创面的多种生理参数,并实现原位在线的多种生理参数检测。A method for detecting multiple physiological parameters of wounds, using the above-mentioned device to multiplex photoelectric detection of multiple physiological parameters, using different wavelengths of light to time-division detect various physiological parameters of wounds, and realizing multiple physiological parameters in situ and online Parameter detection.
相比于现有技术,本发明具有的有益效果为:通过将不同波长的LED一一对应的n种敏感薄膜按照反射光路一一对应的位置布局,利用不同波长的光分时检测创面的多种生理参数,能够实现同时检测多种创面生理参数指标。符合未来生物传感器的发展方向-小型化多功能以及不会给人带来不适感。Compared with the prior art, the present invention has the beneficial effects of: by arranging the n kinds of sensitive films corresponding to LEDs of different wavelengths one by one according to the positions of the reflected light paths, the multiples of the wound surface can be detected by using different wavelengths of light in time division. A variety of physiological parameters can be detected simultaneously. It is in line with the development direction of future biosensors - miniaturization, multi-function and no discomfort.
附图说明Description of drawings
图1是实施例1提供的同时检测创面多种生理参数指标的装置贴覆于创面表面的结构示意图;Fig. 1 is a schematic diagram of the structure of the device for simultaneously detecting multiple physiological parameters of the wound surface provided by Example 1 and attached to the surface of the wound surface;
图2是实施例2提供的同时检测创面多种生理参数指标的装置贴覆于创面表面的结构示意图。Fig. 2 is a schematic diagram of the structure of the device for simultaneously detecting multiple physiological parameters of the wound provided in Example 2 and attached to the surface of the wound.
图3是利用实施例2提供的装置测量的血氧饱和度值分布图;Fig. 3 is a distribution diagram of blood oxygen saturation values measured by the device provided in Example 2;
图4是利用实施例2提供的装置测量的PH值分布图;Fig. 4 is the distribution figure of pH value that utilizes the device measurement that embodiment 2 provides;
图5是利用实施例2中提供的反射式血氧传感器未旋涂敏感薄膜时测量的血氧饱和度值分布图。FIG. 5 is a graph showing the distribution of blood oxygen saturation measured by using the reflective blood oxygen sensor provided in Example 2 without spin-coating the sensitive film.
具体实施方式Detailed ways
为了更为具体地描述本发明,下面结合附图及具体实施方式对本发明的技术方案进行详细说明。In order to describe the present invention more specifically, the technical solutions of the present invention will be described in detail below in conjunction with the accompanying drawings and specific embodiments.
实施例1Example 1
图1是本发明实施例提供的同时检测创面多种生理参数指标的装置贴覆于创面表面的结构示意图。该包括:反射式光电检测模块1、包覆于反射式光电检测模块1表面的透明隔离层薄膜2、旋涂在透明隔离层薄膜2上的PH敏感薄膜31、乳酸敏感薄膜32、葡萄糖敏感薄膜33以及创面8。其中,反射式光电检测模块1中含有敏感薄膜一一对应的最优波长的LED4、LED5、LED6以及光电二极管7。Fig. 1 is a schematic diagram of the structure of a device for simultaneously detecting multiple physiological parameters of a wound provided by an embodiment of the present invention, which is attached to the surface of the wound. This includes: a reflective photoelectric detection module 1, a transparent isolation layer film 2 coated on the surface of the reflective photoelectric detection module 1, a pH sensitive film 31 spin-coated on the transparent isolation layer film 2, a lactic acid sensitive film 32, and a glucose sensitive film. 33 and wound 8. Wherein, the reflective photoelectric detection module 1 includes LED4, LED5, LED6 and photodiode 7 with optimal wavelength corresponding to each sensitive film.
实施例2Example 2
本实施例中,只旋涂一种PH敏感薄膜于透明隔离层薄膜,且将PH敏感薄膜全部涂满在透明隔离层薄膜上。如图2所示,本实施例提供的装置包括:型号为SFH7050的反射式血氧传感器1、包覆于反射式血氧传感器1表面的PDMS 2、旋涂在PDMS 2上的PH敏感薄膜3以及创面8。其中,反射式血氧传感器1中含有红光LED4、绿光LED5、红外LED6以及光电二极管7。In this embodiment, only one kind of pH sensitive film is spin-coated on the transparent isolation layer film, and the pH sensitive film is completely coated on the transparent isolation layer film. As shown in Figure 2, the device provided in this embodiment includes: a reflective blood oxygen sensor 1 of model SFH7050, a PDMS 2 coated on the surface of the reflective blood oxygen sensor 1, and a pH sensitive film 3 spin-coated on the PDMS 2 and wound surface 8. Wherein, the reflective blood oxygen sensor 1 includes a red LED 4 , a green LED 5 , an infrared LED 6 and a photodiode 7 .
PH敏感薄膜3采用溶胶-凝胶技术对溶胶-凝胶前体包覆酸碱指示剂染料分子制备得到。其中,酸碱指示剂染料分子包括溴甲酚绿、溴甲酚绿钠盐、甲基红以及中性红。The pH-sensitive film 3 is prepared by coating the acid-base indicator dye molecules on the sol-gel precursor by sol-gel technology. Wherein, the acid-base indicator dye molecules include bromocresol green, bromocresol green sodium salt, methyl red and neutral red.
溶胶-凝胶前体分为无机前体、有机前体以及有机-无机杂化前体三类,其中,无机前体包括原硅酸四乙酯(TEOS)、四甲氧基硅烷(TMOS);有机前体包括γ-缩水甘油醚氧丙基三甲氧基硅烷(GLYMO)、甲基三乙氧基硅烷(MTES)、乙基三乙氧基硅烷改性(ETES)或苯基三甲氧基硅烷(FTMS);有机-无机杂化前体为有机前体与无机前体以不同比例混合得到。Sol-gel precursors are divided into three types: inorganic precursors, organic precursors, and organic-inorganic hybrid precursors. Among them, inorganic precursors include tetraethylorthosilicate (TEOS), tetramethoxysilane (TMOS) ; Organic precursors include γ-glycidyloxypropyltrimethoxysilane (GLYMO), methyltriethoxysilane (MTES), ethyltriethoxysilane modified (ETES) or phenyltrimethoxy Silane (FTMS); organic-inorganic hybrid precursor is obtained by mixing organic precursor and inorganic precursor in different proportions.
PH敏感薄膜3的厚度为10μm,为了PH敏感薄膜在机械性能、光学透明以及响应时间之间取得最优结果,有机前体与无机前体体积比为3:7(合计1mL)。通过以下方法制备得到:The thickness of the pH-sensitive film 3 is 10 μm. In order to achieve the best results among mechanical properties, optical transparency and response time of the pH-sensitive film, the volume ratio of the organic precursor to the inorganic precursor is 3:7 (1 mL in total). Prepared by the following method:
首先,将1.2mL乙醇、16.3mg溴甲酚绿钠盐、0.3mLγ-缩水甘油醚氧丙基三甲氧基硅烷(GLYMO)、0.7mL原硅酸四乙酯(TEOS)以及0.4mL催化剂(0.1M HCL)混合制备溶胶,然后超声浴匀化10min,室温下老化3天,之后通过旋涂技术旋涂到PDMS上,室温避光条件下放置3天。First, 1.2 mL of ethanol, 16.3 mg of bromocresol green sodium salt, 0.3 mL of γ-glycidyloxypropyltrimethoxysilane (GLYMO), 0.7 mL of tetraethyl orthosilicate (TEOS) and 0.4 mL of catalyst (0.1 M HCL) were mixed to prepare a sol, then homogenized in an ultrasonic bath for 10 min, aged at room temperature for 3 days, and then spin-coated onto PDMS by spin coating technology, and placed at room temperature for 3 days in the dark.
反射式血氧传感器SFH7050中LED发出的光透过隔离层薄膜和敏感薄膜照射到创面上,除去散射和吸收部分,反射光由光电二极管接收并转换成与光强成正比例的电信号,利用动脉血氧饱和度计算公式得出血氧饱和度,电信号中,光通过组织和血管时的吸收情况,可分为脉动成分(如动脉血)和非脉动成分(如皮肤、组织、静脉血等),即可称为交流量(AC)和直流量(DC),由于伤口PH值不会发生骤变,因此PH敏感膜对光的吸收作为DC部分。The light emitted by the LED in the reflective blood oxygen sensor SFH7050 passes through the isolation layer film and the sensitive film to irradiate the wound surface, and the scattering and absorption parts are removed. The reflected light is received by the photodiode and converted into an electrical signal proportional to the light intensity. The blood oxygen saturation calculation formula can be used to obtain blood oxygen saturation, electrical signals, light absorption when passing through tissues and blood vessels, which can be divided into pulsating components (such as arterial blood) and non-pulsating components (such as skin, tissue, venous blood, etc. ), which can be called alternating current (AC) and direct current (DC). Since the pH value of the wound does not change suddenly, the absorption of light by the pH-sensitive membrane is regarded as the DC part.
利用本实施例制备的装置置于创面表面,基于朗伯-比尔定律,利用红光和红外两路LED光测量得到电信号,即光电血管容积图(PPG),通过动脉血氧饱和度计算公式得出血氧饱和度,结果如图3所示。The device prepared in this example is placed on the surface of the wound, and based on the Lambert-Beer law, the electrical signal is obtained by measuring the red light and the infrared LED light, that is, the photoplethysmogram (PPG), and the calculation formula of the arterial blood oxygen saturation The blood oxygen saturation was obtained, and the results are shown in Figure 3.
利用本实施例制备的装置置于不同PH缓冲液中,PH值5-9,间隔为1,使用绿光LED发射的光测量得到的电信号来表征PH大小,结果如图4所示。The device prepared in this example was placed in different pH buffer solutions with a pH value of 5-9 and an interval of 1, and the electrical signal obtained by measuring the light emitted by the green LED was used to characterize the pH value, and the results are shown in FIG. 4 .
利用本实施例提供的反射式血氧传感器未旋涂PH敏感薄膜时置于创面表面,通过红光和红外两路波长光测量得到的PPG信号,结合朗伯-比尔定律计算血氧饱和度。计算公式如下:The reflective blood oxygen sensor provided in this embodiment is placed on the wound surface when the PH sensitive film is not spin-coated, and the PPG signal obtained by measuring the red light and the infrared wavelength light is used to calculate the blood oxygen saturation in combination with the Lambert-Beer law. Calculated as follows:
[HbO2]和[Hb]分别表示含氧血红蛋白和脱氧血红蛋白的浓度。[HbO 2 ] and [Hb] represent the concentrations of oxygenated hemoglobin and deoxygenated hemoglobin, respectively.
α(HbO2,λRed),α(HbO2,λIR),α(Hb,λRed),α(Hb,λIR)分别是HbO2和Hb对α(HbO 2 ,λ Red ),α(HbO 2 ,λ IR ),α(Hb,λ Red ),α(Hb,λ IR ) are the pairs of HbO 2 and Hb respectively
红光和红外的吸收系数。R计算如下:Absorption coefficient for red and infrared light. R is calculated as follows:
根据HbO2/Hb的光谱吸收特性,吸收系数满足以下关系:According to the spectral absorption characteristics of HbO 2 /Hb, the absorption coefficient satisfies the following relationship:
α(Hb,λRed)>>α(HbO2,λRed) (4)α(Hb,λ Red )>>α(HbO 2 ,λ Red ) (4)
α(Hb,λIR)≈α(HbO2,λIR) (5)α(Hb,λ IR )≈α(HbO 2 ,λ IR ) (5)
因此,公式(1)可以简化为:Therefore, formula (1) can be simplified as:
使用商用光电血氧计校准A和B。Calibrate A and B using a commercial photo-oximeter.
经上式计算得到血氧饱和度,结果如图5所示。对应每次测量结果,本发明实施例提供的检测创面多种生理参数指标的装置与未旋涂PH敏感薄膜测试得到的血氧饱和度仅有0.1%-0.2%的差别。该结果表明PH敏感薄膜的存在不影响血氧饱和度的测量。The blood oxygen saturation was calculated by the above formula, and the result is shown in Figure 5. Corresponding to each measurement result, there is only a difference of 0.1%-0.2% in blood oxygen saturation between the device for detecting multiple physiological parameters of the wound surface provided by the embodiment of the present invention and the non-spin-coated pH-sensitive film test. This result indicates that the presence of the pH-sensitive film does not affect the measurement of blood oxygen saturation.
因此,本实施例能实现原位在线检测创面动脉血氧饱和度和PH值。Therefore, this embodiment can realize the in-situ online detection of the arterial blood oxygen saturation and pH value of the wound.
以上所述的具体实施方式对本发明的技术方案和有益效果进行了详细说明,应理解的是以上所述仅为本发明的最优选实施例,并不用于限制本发明,凡在本发明的原则范围内所做的任何修改、补充和等同替换等,均应包含在本发明的保护范围之内。The above-mentioned specific embodiments have described the technical solutions and beneficial effects of the present invention in detail. It should be understood that the above-mentioned are only the most preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, supplements and equivalent replacements made within the scope shall be included in the protection scope of the present invention.
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