Patent Application: US-201514929311-A

Abstract:
the present invention relates to systems and methods using optical or electrical spectroscopy for accurate detection and monitoring of biological tissue properties in a noninvasive manner . to perform in vivo diagnose with more accurate and repeatable measurements , an air - tight micro suction cup is placed against biological tissue under test , around which an electrical or optical sensing system comprising excitation and detection sensors is integrated . applying a high power suction pump over the micro cup , a negative pressure is generated to reshape the skin covered by the cup to a contour suitable for better measurement results . most important , as the suction power increases , certain amount of blood flow or body fluid is brought to skin layer , providing great potential of improving those diagnoses that require direct analysis over these biological components .

Description:
referring more specifically to the drawings , for illustrative purposes the present invention is embodied in the methods and apparatus a generally shown in fig1 through fig1 . it will be appreciated that the apparatus may vary as to configuration and as to details of the parts , and that the method may vary as to the specific steps and sequence , without departing from the basic concepts as disclosed herein . referring now to fig1 , a first non - invasive biological sensing system 10 is schematically described in accordance with the present invention . the device 10 comprises an excitation or transmitting source 102 coupled to a first light guide 104 , such as a fiber optic unit , to direct and transport excitation light 106 to the biological tissue under measurement , such as skin 108 of a strategically selected area of the human body . the light signal 110 that is scattered from the tissue under test is collected and transported by a second light guide 112 to an receiving optical sensor ( or light detector ) 114 , wherein the light signal is converted to electric signal and sent to the computer analysis unit 116 . as means of improve measurement accuracy and repeatability , a micro suction cup 118 , is placed between the light entry and exit points , with opening facing to the surface of the skin . the suction cup is made air tight by the seal ring 120 . by connecting a high power air pump 122 , the air inside the micro cup is pumped out , generating suction pressure 124 that raises up the skin surface 126 to a desirable contour . with sufficiently high suction pressure , the blood flow ( or body fluid ) 128 is brought to the skin layer , improving those diagnoses that typically require analysis over the blood or body fluid . the suction pump 122 described in fig1 performs suction to get the air out of the sealed cup . it can be mechanical operating manually , or electrical powered by an electrical motor . the computer unit 116 described in fig1 performs the analysis over the data collected from the receiving sensor and delivers the diagnose result . the analysis may include near infrared spectral imaging , raman or fluorescence spectroscopy , or other type of optical based spectral analysis methods . referring to fig2 , the micro suction cup 118 in fig1 further comprises a cup - shaped capsule 202 with an opening 204 , which is placed against the sample under test . the capsule can be typically made of glass , plastic , steel or other solid materials . a seal ring 120 , which is typically made of rubber or silicon , or other type of sealing materials , is attached to the opening to keep air - tight between the skin and the capsule . there is also small opening 206 to connect to the air suction pump . located at bottom of the cup , closing to the skin , 208 and 210 , are used to connect the excitation source and receiving sensor respectively . wherever devices are connected to the capsule , air - tight seal needs to be maintained at each of the openings . a release valve 212 is placed somewhere on the cup to release the suction when the measurement is complete . the micro suction cup device can be shaped differently to meet custom needs . for example , fig3 shows a design of shadow cylinder shape to reduce the size , where the block 202 , 204 , 206 , 208 , 210 , and 120 have the same functionality as in fig2 . fig4 describes the procedure of operating the cup sensing system in an in vivo manner . in a first step 402 of the procedure , the micro cup is properly mounted at the selected skin area of interest . the cup opening with seal ring ( 120 in fig1 ) has to be placed against the skin with sufficient tightness so that air - tight sealing is ensured . in case of non - flat skin area at some locations , the opening shape can be specially made to follow the contour of human body . in a second step 404 of the procedure , the excitation source , receiving sensor , and computer unit ( 102 , 114 , 106 in fig1 ) are all turned on . when all these units reach steady state ready for operation , the computer unit starts to collect certain amount of data for calibration purpose . the computer may also optionally give an indication if the cup sensing system is appropriately mounted . in a third step 406 of the procedure , the suction pump is activated . when skin inside the cup is raised up to a desired level because of the suction , the suction pump is stopped . in a fourth step 408 of the procedure , the computer starts to collect data while the skin level inside the cup is maintained . in a fifth step 410 of the procedure , the release valve ( 212 in fig2 ) is pressed to release the suction when sufficient data is taken by the computer unit . in a sixth step 412 of the procedure , the computer unit performs analysis over the data collected in step 408 . the data captured during calibration step 404 may be optionally used to improve the diagnose outcome . fig4 specifies the operation of the biological sensing system in more precise and detailed manner , it is understood , however , one or some steps may be optionally omitted and the order of the execution of the steps may vary in actual implementation . referring now to fig5 , a second non - invasive biological sensing system 50 , which is using the electrical sensors , is schematically described in accordance with the present invention . the device 50 comprises an electrical excitation source 502 connected to , via an electrical wire 504 , to an excitation probe 506 . the excitation source 502 can typically generate electrical signals such as dc , ac , impulse , or other types of signal waveforms . the excitation probe 506 is passing through the small opening of the micro suction cup 118 ( described in fig2 ) to be directly in touch with the skin area 126 under test . at the other opening of the micro suction cup 118 , a sensing probe 508 is installed , which is connected , via electrical wire 510 , to the computer analysis unit 512 . the computer unit 512 therefore can process the electrical signal received , such as providing impedance or dielectric analysis . the rest items in fig5 , including 118 , 120 , 124 , 126 and 128 , can be similarly described as in fig1 and fig2 , and the corresponding operation procedure also follows the steps given in fig4 . the micro cup sensing system can be extended to a design of using sensor arrays , where a plurality of receiving sensors deployed around the cup generate a plurality of signals sent to the computer unit in order to improve the diagnose accuracy . fig6 and fig7 show such designs using optical and electrical sensors respectively . referring to fig8 , a third non - invasive biological sensing system 80 , which is using a feedback control over the air pressure inside the suction cup , is schematically described in accordance with the present invention . the system 80 comprises a first link 808 that connects the computer unit 806 to the suction pump 802 , and second link 810 that connects the computer unit 806 to the release valve 804 . based on the measurement results , the computer unit dynamically controls ( such as switch on and off ) the suction pump and the release valve via the feedback links , in order to achieve optimal pressure inside the suction cup for best diagnose results . as an option , the release valve should be manually controlled to override suction process anytime during the feedback procedure . as another option , a pressure sensor can be installed inside the suction cup and connected to the computer unit , in order to accurately control the suction pressure to a desired level . note that fig8 shows an example of the feedback suction cup system using optical sensors . it should be directly applicable to other variations of the designs described in this invention disclosure , such as the sensor systems using electrical sensors , or using sensor arrays . an operation procedure 90 of the suction feedback control is shown in fig9 . the procedure is essentially based on all the steps described in fig4 , except that additionally steps are added for the feedback control of the suction pressure . in a first additional step 902 , the receiving sensor collects measurement data received from the tissue under test after the air suction step . in a second additional step 904 , a real time analysis 904 over the measured data is performed by the computer unit 806 referred in fig8 . in a third additional step 906 , the computer unit decides whether suction pressure adjustment is need based on the analysis results . if decision is no , the procedure will proceed further steps including release the suction and post processing , using similar steps described in fig4 . otherwise , the computer unit will further decide whether the suction pressure needs be increased or decreased in a fourth additional step 908 . for increasing the suction pressure , the computer unit , via the feedback link 808 in fig8 , switches on the suction pump in a fifth step 910 for a controlled time period , and for decreasing the suction pressure , the computer unit , via the feedback link 810 , partially opens the release valve in a sixth additional step 912 for another controlled time period . after these steps , the measurement is retaken in step 902 and the aforementioned step cycle repeats until decision is made by the computer unit that no further suction pressure adjustment is needed . as an option of the first additional step 902 , the measurement data is taken from an optional pressure sensor installed inside the suction cup and the third additional step 906 makes decision based on the measured pressure level , in order to precisely control the suction pressure to a desired value . referring fig1 , a heating device 1002 is deployed inside the suction cup to raise the air temperature for different diagnose purposes . a thermal meter 1004 can also be installed inside the suction cup for controlling the temperature . both 1002 and 1004 are controlled by the computer unit 1010 via the wire connections 1006 and 1008 . clearly , a temperature adjustment by a feedback procedure can be designed to maintain the temperature to a desired value . referring fig1 , a humility sensor 1101 is deployed inside the suction cup to measure the humility of the skin under test . the humility sensor 1101 is placed tightly against the surfaced of the tissue under test , such as skin of a human body , in order to provide analysis of its water contents . this humility sensor is connected to the computer unit 1103 via the wire 1102 . in fig1 , an interdigital - shaped humility sensor is applied as an example . other types of humility sensor can also be utilized . referring fig1 , an auxiliary sensor 1204 , which can be either optical or electrical , is deployed to the suction cup sensing system for the purpose of calibration . this sensor also receives the signal emitted by the excitation source 1202 , passing through an attenuator 1201 connected by links 1203 and 1204 . the attenuator 1201 is made of the material of known and constant optical or electrical property . for example , the attenuator has a known optical absorption coefficient for any of the optical sensing systems described in the disclosure . the auxiliary sensor 1204 further feeds the detected signal to the computer unit 1206 for processing . fig1 describes the procedure 120 whereas the humidity sensor and the calibration auxiliary sensor are applied to any of the biological glucose sensing systems described in this embodiment . in a first step 1301 of the procedure , the main receiving sensor that is connected to skin under test in the suction cup , collects a spectrum of signals ( which can be either optical or electrical ) at different wavelengths or frequencies , and send it to the computer unit of the sensing system . in a second step 1302 of the procedure , the auxiliary sensor collects second spectrum of signals and sends it to the computer unit . though described in two separate steps , the step 1301 and 1302 occurs concurrently when the excitation source described in any of the sensing systems in this embodiment emits at given frequencies or wavelengths . in a third step of the procedure 1303 , a compensation factor is calculated from the input of the auxiliary sensor and the attenuation coefficients stored in the computer at each frequency or wavelength point . as a simple example , assume sa ( f ) is the input from the auxiliary detector and the r ( f ) as the constant attenuator coefficient at frequency f , the compensation factor c ( f ) is calculated by c ( f )=| sa ( f )|/ r ( f ), whereas | sa ( f )| represents the amplitude of signal from the auxiliary sensor . other non - linear algorithm can also applied to calculated c ( f ). in a fourth step of the procedure , the signal from the main sensor is normalized by the compensation factor calculated by 1303 . in a fifth step 1305 of the procedure , the humility sensor senses the humility of the skin and sends the signal also to the computer unit . this step can occur before or after , or same time as , the step 1301 . in a sixth step of the procedure 1206 , the computer unit selects a set of reference signature from the database 1311 based on the sensed humility level . this set of signature consists of a series of reference spectrum calibrated beforehand in terms of various concentration level of the biological tissue property under measurement , such as glucose . in a seventh step of the procedure 1307 , the computer unit correlates the received spectrum with the selected reference signature set and calculates a plurality of decision metrics , corresponding to each member of the reference signature set . as an example , the correlation algorithm can be partial linear regression ( plr ) or principle component regression ( pcr ). in a eighth step of the procedure 1308 , a single metric is selected among the calculated decision metrics according to a optimum criterion , such as a maximum rule or any other nonlinear algorithm . at last step 1206 of the procedure , this selected decision metric is uniquely mapped to the concentration level of the measured biological tissue property from a pre - calibrated table . fig1 specifies the operation of the calibration and humility sensors in a general manner , it is understood , however , one or some steps may be optionally omitted and the order of the execution of the steps may vary in actual implementation . the apparatus and methods disclosed in the entire embodiment of this invention are mainly focusing on noninvasive blood glucose sensing and monitoring via a suction cup sensing system directly applied to skin of a human body . it will be more appreciated , however , that the same methods and techniques can be directly applied to sensing and monitoring other types of biological tissue properties that partially needs in - depth access to the body tissue , such as blood . examples of the biological tissue properties may be some clinically important blood analytes such as albumin , cholesterol , or urea . american diabetes association , ( 2010 ) “ diagnosis and classification of diabetes mellitus ”, diabetes care , vol . 33 , pp . s62 - 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