Abstract:
Needle-less extraction of a biospecimen from tissue having a number of tissue layers including an epidermis layer includes creating a first port through a target surface and into an underlying one of the tissue layers, creating a second port through the target surface and into the underlying one of tissue layers, providing an injectate through the first port to the underlying one of the tissue layers underlying the epidermis layer, and extracting at least a portion of the injectate and the biospecimen from the underlying one of the layers through the second port.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims priority to U.S. application Ser. No. 62/267,339, filed on Dec. 15, 2015, the contents of which are incorporated herein by reference. 
     
    
     BACKGROUND 
       [0002]    This invention relates to a biospecimen extraction apparatus and a method for biospecimen extraction. 
         [0003]    Conventional biospecimen extraction techniques (e.g., interstitial fluid extraction techniques) often use invasive and painful tools such as needles to puncture the skin of a patient for the purpose of biospecimen extraction. 
       SUMMARY 
       [0004]    In a general aspect, a needle-free method of extracting interstitial fluid from upper tissue layers for diagnostic purposes uses two needle-free ports. Two jets originating from the two ports create a port for an injectable fluid to pass into the skin and to create a second port for the injectable fluid, intermingled with a biospecimen, to be ejected or passed back out of the skin. 
         [0005]    In another general aspect, a method for needle-less extraction of a biospecimen from tissue having a number of tissue layers including an epidermis layer includes creating a first port through a target surface and into an underlying one of the number of tissue layers, creating a second port through the target surface and into the underlying one of number of tissue layers, providing an injectate through the first port to the underlying one of the number of tissue layers underlying the epidermis layer, and extracting at least a portion of the injectate and the biospecimen from the underlying one of the layers through the second port. 
         [0006]    Aspects may include one or more of the following features. 
         [0007]    Creating the first port and creating the second port may occur substantially simultaneously. The first port may be created at a first depth relative to a surface of the epidermis and the second port may be created at a second depth relative to the surface of the epidermis. The first depth and second depth may be substantially the same. The first port may be created at a first angle relative to the target surface and the second port may be created at a second angle relative to the target surface. The number of the tissue layers may include a dermis layer and a subcutaneous layer underlying the epidermis layer. 
         [0008]    The underlying one of the number of tissue layers may be in the dermis layer. The underlying one of the number of tissue layers may be in the subcutaneous layer. Creating the first port may include using a first needle-less injection device and creating the second port may include using a second needle-less injection device. Creating the first port and creating the second port may occur substantially simultaneously. Creating the first port may include using the first needle-less injection device and creating the second port may include using the first needle-less injection device. 
         [0009]    The method may include, after creating the first port with the first needle-less injection device, moving the first needle-less injection device, followed by creating the second port with the first needle-less injection device. The biospecimen may be a fluid. The fluid may be an extracellular fluid or a cerebrospinal fluid. Tissue may be selected from a group consisting of muscle, cartilage, and organ. The injectate may be a fluid. The fluid may be gaseous. 
         [0010]    In another general aspect, a needle-less biospecimen extraction apparatus includes a housing having a distal end, one or more chambers disposed within the housing. Each chamber of the one or more chambers has a plunger disposed therein. A first opening is disposed in the distal end of the housing and is in fluid communication with a chamber of the one or more chambers via a first channel. A second opening is disposed in the distal end of the housing and is in fluid communication with a chamber of the one or more chambers via a second channel. The second opening is spatially separated from the first opening by a first distance and the second channel is arranged at an angle relative to the first channel. The first distance and the angle determine a second distance from the distal end of the housing at which a first jet of fluid ejected from the first opening intersects with a second jet of fluid ejected from the second opening. The apparatus also includes an actuator mechanism for moving the plunger of each chamber of the one or more chambers along a length of the chamber and a controller for controlling the actuator mechanism to move the plunger of each chamber of the one or more chambers according to a biospecimen extraction profile. 
         [0011]    Aspects may include one or more of the following features. 
         [0012]    The one or more chambers may include a first chamber in fluid communication with the first opening via the first channel and a second chamber in fluid communication with the second opening via the second channel. The one or more chambers may include a first chamber in selective fluid communication with the first opening via the first channel and in selective fluid communication with the second chamber via the second channel. The apparatus may further include a valve for placing one of the openings into fluid communication with the first chamber and for preventing fluid communication of the other of the openings and the first chamber. 
         [0013]    Other features and advantages of the invention are apparent from the following description, and from the claims. 
     
    
     
       DESCRIPTION OF DRAWINGS 
         [0014]      FIG. 1  is a schematic diagram of a first biospecimen extraction apparatus. 
           [0015]      FIG. 2  is a biospecimen extraction profile for the biospecimen extraction apparatus of  FIG. 1 . 
           [0016]      FIG. 3  shows the biospecimen extraction apparatus of  FIG. 1  performing the first step of the biospecimen extraction profile of  FIG. 2 . 
           [0017]      FIG. 4  shows the biospecimen extraction apparatus of  FIG. 1  performing the second step of the biospecimen extraction profile of  FIG. 2 . 
           [0018]      FIG. 5  shows the biospecimen extraction apparatus of  FIG. 1  performing the third step of the biospecimen extraction profile of  FIG. 2 . 
           [0019]      FIG. 6  is a schematic diagram of a second biospecimen extraction apparatus. 
           [0020]      FIG. 7  is a biospecimen extraction profile for the biospecimen extraction apparatus of  FIG. 6 . 
           [0021]      FIG. 8  shows the biospecimen extraction apparatus of  FIG. 6  performing the first step of the biospecimen extraction profile of  FIG. 7 . 
           [0022]      FIG. 9  shows the biospecimen extraction apparatus of  FIG. 6  performing the second step of the biospecimen extraction profile of  FIG. 7 . 
           [0023]      FIG. 10  shows the biospecimen extraction apparatus of  FIG. 6  performing the third step of the biospecimen extraction profile of  FIG. 7 . 
       
    
    
     DESCRIPTION 
       [0024]    Referring to  FIG. 1 , a needle-free biospecimen extraction apparatus  100  is configured to extract a biospecimen from a patient without the use of needles or other invasive sampling devices. 
         [0025]    The apparatus  100  includes a housing  102  having a first chamber  104  and a second chamber  106  disposed therein. A distal end  108  of the housing  102  includes a first opening  110  that is in fluid communication with the first chamber  104  via a first channel  111  and a second opening  112  that is in fluid communication with the second chamber  106  via a second channel  113 . It is noted that a distance, ζ exists between the first opening  110  and the second opening  112 , and an angle, φ exists between the first channel  111  and the second channel  113 . The distance, ζ and the angle, φ are specified to ensure that jets of fluid ejected from the first opening  110  and the second opening  112  intersect at a predetermined depth under a target surface (e.g., the epidermis) on a patient&#39;s skin. 
         [0026]    The first chamber  104  has a first plunger  114  disposed therein and the second chamber  106  has a second plunger  116  disposed therein. The first plunger  114  and the second plunger  116  are independently movable along the lengths of their respective chambers  104 ,  106  by one or more electromechanical actuators  118  (e.g., linear actuators). A direction and speed of the movement of the plungers  114 ,  116  is controlled by a controller  120  according to a biospecimen extraction displacement profile. 
         [0027]    Referring to  FIG. 2 , one example of a biospecimen extraction displacement profile  200  shows a displacement of both the first plunger (i.e., X 1 )  114  and the second plunger (i.e., X 2 )  116  over time. According to the displacement profile  200  of  FIG. 2 , the controller  120  controls the plungers  114 ,  116  through three stages, a first stage from times t 0  to t 1 , a second stage from times t 1  to t 2 , and a third stage from times t 2  to t 3 . 
         [0028]    Referring to  FIG. 3 , during the first stage of the displacement profile  200 , at a time to the plungers  114 ,  116  are at a starting displacement in their respective chambers  104 ,  106 . The controller  120  causes the electromechanical actuator(s)  118  to move both of the plungers  114 ,  116  toward the distal end  108  of the housing  102 , thereby causing ejection of any fluid in the chambers  104 ,  106  (e.g., air or a liquid such as saline) out of the chambers via the openings  110 ,  112 . The ejection of fluid through openings  110 , results in two jets  122 ,  124  of fluid which pierce an epidermis  126  of the patient&#39;s skin and intersect at a predetermined depth underneath the patient&#39;s skin (in this case, in the dermal layer  128 ). At the conclusion of the first stage, t 1 , a port  130  is established between the first opening  110  and the second opening  112  via the patient&#39;s epidermis  126  and dermal layer  128 . 
         [0029]    Referring to  FIG. 4 , at the beginning of the second stage of the displacement profile  200  (i.e., at time t 1 ), the controller  120  causes the electromechanical actuator(s)  118  to continue moving the first plunger  114  in a direction toward the distal end  108  of the housing  102  but reverses the direction of the second plunger  116  such that it moves in a direction away from the distal end  108  of the housing  102 . This causes the first jet of fluid  122  to continue to force fluid into the port  130 . The reversal of the movement of the second plunger  116  causes the second jet of fluid  124  to stop flowing and creates a vacuum at the second opening  112 . The combination of the first jet  122  flowing out of the first opening  110  into the port  130  and the vacuum at the second opening  112  causes fluid to be drawn through the port  130  and into the second chamber  106 . As the fluid is drawn through the port  130 , it intermingles with a biospecimen (e.g., interstitial fluid) such that the fluid drawn into the second chamber  106  includes the biospecimen. 
         [0030]    Referring to  FIG. 5 , at the beginning of the third stage of the displacement profile  200  (i.e., at time t 2 ), the controller  120  stops movement of the first plunger  116  in the first chamber  104  and continues movement of the second plunger  116  in a direction away from the distal end  108  of the housing, thereby drawing an additional amount of biospecimen from the patient. 
         [0031]    Referring to  FIG. 6 , another embodiment of a needle-free biospecimen extraction apparatus  600  is configured to extract a biospecimen from a patient without the use of needles or other invasive sampling devices. 
         [0032]    The apparatus  600  includes a housing  602  having a chamber  604  disposed therein. A distal end  608  of the housing  602  includes a first opening  610  that is in fluid communication with the chamber  604  via a first channel  611  and a second opening  612  that is in fluid communication with the chamber  604  via a second channel  613 . It is noted that a distance, ζ exists between the first opening  610  and the second opening  612 , and an angle, φ exists between the first channel  611  and the second channel  613 . The distance, ζ and the angle, φ are specified to ensure that jets of fluid ejected from the first opening  610  and the second opening  612  intersect at a predetermined depth under the surface of a patient&#39;s skin. A flap (or valve)  615  is disposed at an outlet of the chamber  604  and is controlled (e.g., by a controller  620 ) to establish fluid communication between one of the channels  611 ,  613  and the chamber  604  and to block fluid communication between the other of the channels  611 ,  613  and the chamber  604 . That is, the flap  615  causes only one of the channels  611 ,  613  to be in fluid communication with the chamber  604  at a time. 
         [0033]    The chamber  604  has a plunger  614  disposed therein. The plunger  614  movable along the length of the chamber  604  by one or more electromechanical actuators  618  (e.g., linear actuators). A direction and speed of the movement of the plunger  614  is controlled by the controller  620  according to a biospecimen extraction displacement profile. 
         [0034]    Referring to  FIG. 7 , one example of a biospecimen extraction displacement profile  700  shows a displacement of the first plunger  614  (i.e., X 1 ) over time. According to the displacement profile  700  of  FIG. 7 , the controller  620  controls the plunger  614  through three stages, a first stage from times t 0  to t 1 , a second stage from times t 1  to t 2 , and a third stage from times t 2  to t 3 . 
         [0035]    Referring to  FIG. 8 , during the first stage of the displacement profile  700 , at a time to the plunger  614  is at a starting displacement in the chamber  604 . The flap  615  is positioned such that the first channel  611  and the first opening  610  are in fluid communication with the chamber  604  and fluid communication between the second channel  613 , the second opening  612 , and the chamber  604  is blocked. 
         [0036]    The controller  620  causes the electromechanical actuator(s)  618  to move the plunger  614  toward the distal end  608  of the housing  602 , thereby causing ejection of fluid in the chamber  604  (e.g., air or a liquid such as saline) out of the chamber  604  via the first opening  610 . The ejection of fluid through the first opening  610  results in a jet  622  of fluid which pierces an epidermis  626  of the patient&#39;s skin, and creates a first part of a port  630  into the patient&#39;s dermal layer  628 . At the conclusion of the first stage, t 1 , the first part of the port  630  is established. 
         [0037]    Referring to  FIG. 9 , during the second stage of the displacement profile  700 , at time t 1  the flap  615  is repositioned (e.g., by the controller  620 ) such that the second channel  613  and the second opening  612  are in fluid communication with the chamber  604  and fluid communication between the first channel  611 , the first opening  610 , and the chamber  604  is blocked. 
         [0038]    The controller  620  continues to cause the electromechanical actuator(s)  618  to move the plunger  614  toward the distal end  608  of the housing  602 , thereby causing ejection of fluid in the chamber  604  out of the chamber  604  via the second opening  612 . The ejection of fluid through the second opening  612  results in a jet  624  of fluid which pierces the epidermis  626  of the patient&#39;s skin and creates a second part of the port  630  into the patient&#39;s dermal layer  628 . At the conclusion of the second stage, t 2  the port  630  between the first opening  610  and the second opening  612  via the patient&#39;s epidermis  626  and dermal layer  628  is fully established. 
         [0039]    Referring to  FIG. 10 , during the third stage of the displacement profile  700 , the controller  620  causes the electromechanical actuator(s)  618  to reverse the direction of the plunger  614  such that it moves in a direction away from the distal end  608  of the housing  602 . This creates a vacuum at the second opening  612  which in turn causes fluid to be drawn through the port  630  and into the chamber  604 . As the fluid is drawn through the port  630 , it intermingles with a biospecimen (e.g., interstitial fluid) such that the fluid drawn into the chamber  604  includes the biospecimen. 
       ALTERNATIVES 
       [0040]    In the examples described above, the angle between the device&#39;s channels and the distance between the device&#39;s openings are configured such that a port is established through the patient&#39;s epidermis and dermal layer. However, it is noted that other configurations of the angle between the device&#39;s channels and the distance between the device&#39;s openings may be used to achieve ports with different depths into the patient&#39;s skin. For example, certain configurations may cause the port to extend into the patient&#39;s subcutaneous space or into the patient&#39;s muscle. 
         [0041]    In some examples, the device may be used to obtain cerebrospinal fluid in a needle-free manner. 
         [0042]    In some examples, suction is used to extract the biospecimen from the port in the patient&#39;s tissue. In other examples, the biospecimen is ejected from the port in the patient&#39;s skin and is collected. 
         [0043]    It is to be understood that the foregoing description is intended to illustrate and not to limit the scope of the invention, which is defined by the scope of the appended claims. Other embodiments are within the scope of the following claims.