Patent Publication Number: US-2023137549-A1

Title: Dermal Patch for Collecting a Physiological Sample

Description:
RELATED APPLICATIONS 
     The present application is a continuation-in-part of U.S. patent application Ser. No. 17/903,802 (entitled Dual Lever Dermal Patch System and filed on Sep. 6, 2022), Ser. No. 17/500,873 (entitled Mono Dose Dermal Patch for Pharmaceutical Delivery and filed on Oct. 13, 2021), Ser. No. 17/994,454 (entitled Dermal Patch for Collecting a Physiological Sample and filed on Nov. 28, 2022), Ser. No. 17/971,142 (entitled Dermal Patch for Collecting a Physiological Sample and filed on Oct. 21, 2022), and Ser. No. 17/991,284 (entitled Dermal Patch for Collecting a Physiological Sample with Removable Vial and filed on Nov. 21, 2022). Each of these applications is herein incorporated by reference in its entirety. 
    
    
     TECHNICAL FIELD 
     The present teachings are generally directed to dermal patch systems that can be employed to collect a physiological sample from a subject. 
     BACKGROUND 
     Biomarkers are increasingly employed for diagnosis of various disease conditions as well as for assessing treatment protocols. In many cases, it is important to monitor the level of a biomarker over time (e.g., to assess the progression of a disease). The temporal monitoring of biomarkers via conventional techniques includes drawing a physiological fluid sample from a subject. These techniques may be cumbersome and painful to the subject. For example, the invasive nature of drawing a blood sample from a subject can cause discomfort and may lead to less cooperation from a subject, especially children, rendering multiple measurements of a target analyte difficult. 
     Some recently developed devices allow for continuous monitoring of a target analyte (e.g., glucose monitors). Unfortunately, these devices typically suffer from several shortcomings, such as low sensitivity and/or specificity. 
     SUMMARY 
     Aspects of the present disclosure address the above-referenced problems and/or others. 
     A dermal patch system for collecting a physiological sample includes a cartridge configured to attach to the skin of a subject. The cartridge includes a bottom material layer, a middle material layer, a top material layer, and a sample collection pad. The top layer and the middle layer are coupled to one another and define a vacuum pin receptacle and the vacuum pin is disposed within the vacuum pin receptacle. The vacuum pin creates a vacuum within the cartridge when moved form an undeployed position to a deployed position. The system further includes a lancet with a needle or as many as three needles. The lancet is configured to move the needle(s) from an undeployed position to a deployed position when the lancet is pushed into the cartridge. The needle(s) is configured to direct a physiological sample from the subject when the needle(s) is in the deployed position. The vacuum created by the vacuum pin draws the physiological sample to the sample collection pad. In certain embodiments, the lancet is separate from the cartridge. In some embodiments, capillary flow, wicking and gravity assist the vacuum pin in drawing the physiological sample towards the collection pad. 
     In some embodiments, the lancet is configured to automatically move the needle(s) to the deployed position when pushed into the cartridge to puncture the skin of a subject. In certain embodiments, the lancet is configured to automatically retract the needle(s) into the lancet from the deployed position. In certain embodiments, the cartridge includes a desiccant. In some embodiments, the bottom layer and the middle layer define a sample well configured to retain the drawn physiological sample. In certain embodiments, the sample well is configured to retain about 60 μl of physiological fluid. In some embodiments, the top layer includes a needle aperture and the needle(s) extends through the needle aperture and the sample well to draw the physiological sample. In certain embodiments, the cartridge includes a sample pathway in open communication with the sample well and the sample collection pad. The sample pathway is configured to carry the physiological sample from the sample well to the sample collection pad. 
     In certain embodiments, the sample collection pad rests upon the top surface of the middle layer. In some embodiments, the sample collection pad is disposed vertically above the sample pathway. In certain embodiments, the sample pathway extends through the bottom layer and the middle layer. In some embodiments, the cartridge further includes a vacuum pathway in open communication with the sample collection pad. Moving the vacuum pin to the deployed position creates the vacuum within the vacuum pathway and the sample pathway. In certain embodiments, the vacuum pathway extends through the bottom layer and the middle layer. In some embodiments, the sample collection pad is a CF12 collection pad or cellulose paper. In certain embodiments, the cartridge further includes a quick response code disposed on the top layer, wherein the quick response code is associated with an electronic medical record. In some embodiments, the cartridge further includes an adhesive seal that covers the sample collection pad and seals the cartridge. In some embodiments, the sample collection pad is a first sample collection pad and the cartridge includes a second sample collection pad and the vacuum draws the physiological sample to the first sample collection pad and the second sample collection pad. 
     In another aspect, a method for collecting a physiological sample from a subject, includes attaching a cartridge to a subject. The cartridge includes a bottom material layer, a middle material layer, a top material layer, a sample collection pad, and a vacuum pin. The top layer and middle layer define a vacuum pin receptacle. The vacuum pin is disposed within the vacuum pin receptacle. The method further includes pushing a lancet into the cartridge to draw a physiological sample and pulling the vacuum pin to a deployed position to draw the drawn physiological sample to the sample collection pad. In some embodiments, the lancet is separate from the cartridge. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Aspects of the present disclosure may take form in various components and arrangements of components, and in various steps and arrangements of steps. The drawings are only for illustration purpose of preferred embodiments of the present disclosure and are not to be considered as limiting. 
       Features of embodiments of the present disclosure will be more readily understood from the following detailed description take in conjunction with the accompanying drawings in which: 
         FIG.  1    depicts a dermal patch system in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  2    depicts a lancet of the dermal patch system in accordance with an exemplary embodiment of the present disclosure; 
         FIGS.  3 A and  3 B  depict a housing of the lancet in accordance with an exemplary embodiment of the present disclosure; 
         FIGS.  4 A and  4 B  depict a cap of the lancet in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  5    depicts an inner sleeve of the lancet in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  6    depicts a needle frame of the lancet in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  7    is an exploded view of a cartridge of the dermal patch system in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  8    depicts an adhesive layer of the cartridge in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  9    depicts a bottom layer of the cartridge in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  10    depicts a middle layer of the cartridge in accordance with an exemplary embodiment of the present disclosure; 
         FIGS.  11  and  12    depict a top layer of the cartridge in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  13    depicts the adhesive layer and the bottom layer of the cartridge in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  14    depicts the adhesive layer, the bottom layer, and the middle layer of the cartridge in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  15    depicts the bottom layer, the middle layer, and the top layer of the cartridge in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  16    depicts the top layer and the middle layer of the cartridge in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  17    depicts the cartridge of the dermal patch system with sample collection pads in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  18    depicts the middle layer and the sample collection pads in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  19    depicts the bottom of the cartridge of the dermal patch system in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  20    depicts a vacuum pin of the cartridge in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  21    depicts the lancet of the dermal patch system in an undeployed position in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  22    depicts the lancet of the dermal patch system in a deployed position in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  23    depicts the lancet of the dermal patch system in a retracted position in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  24    depicts the lancet pushed into the cartridge, wherein the lancet is in a deployed position in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  25    depicts the lancet pushed into the cartridge, wherein the lancet is in a refracted position in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  26    depicts the lancet pushed into the cartridge, wherein the lancet is in a refracted position and a vacuum pin is in a deployed position in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  27    diagrammatically depicts an electronic medical record database, a computer system, and a cartridge with a quick response (“QR”) code in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  28    diagrammatically depicts a computer system in accordance with an exemplary embodiment of the present disclosure; 
         FIG.  29    diagrammatically depicts a cloud computing environment in accordance with an exemplary embodiment of the present disclosure; and 
         FIG.  30    is a flow chart of a method for running a diagnostic test on a drawn physiological sample in accordance with an exemplary embodiment of the present disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     The present disclosure generally relates to a dermal patch system (which may also be referred to as a “dermal patch”) that may be utilized to collect and optionally store a physiological sample. 
     In various embodiments, a dermal patch system may be used to collect a physiological sample and the collected sample may then be stored on a sample collection pad of the dermal patch system. Dermal patch systems disclosed herein may allow for the collection and analysis of a physiological sample in a variety of environments (e.g., at home, in the field, in a medical facility, etc.). 
     The term “about,” as used herein, denotes a deviation of at most 10% relative to a numerical value. For example, about 100 μm means in the range of 90 μm-110 μm. 
     The term “substantially,” as used herein, refers to a deviation, if any, of at most 10% from a complete state and/or condition. 
     The term “subject” as used herein refers to a human subject or an animal subject (i.e., chicken, pig, cattle, dog, cat, etc.). 
     The term “transparent,” as used herein, indicates that light can substantially pass through an object (e.g., a window) to allow visualization of a material disposed behind the object. For example, in some embodiments, a transparent object allows the passage of at least 70%, or at least 80%, or at least 90% of visible light therethrough. 
     The term “needle” as used herein, refers to a component with a pointed tip that is configured to pierce an outer surface of an element (e.g., skin of a subject) to provide a passageway through which a physiological fluid can be extracted. 
     The term “vacuum,” as used herein, refers to a pressure less than atmospheric pressure and more particularly to a pressure that can facilitate the movement of a fluid (e.g., a physiological sample) within a dermal patch system according to various embodiments. 
     The present disclosure generally relates to a device, which is herein also referred to as a dermal patch or a dermal patch system, for collecting a physiological sample (e.g., bodily fluids such as blood, interstitial fluids, etc.) from a subject. In some embodiments discussed below, such a dermal patch system can include a cartridge that can be affixed to a subject&#39;s skin (e.g., via an adhesive layer) and a separate lancet that can be engaged with the cartridge to puncture the skin, thereby providing a passageway for extracting the physiological sample. As discussed in more detail below, the lancet can include a housing in which at least one needle that is configured for puncturing the skin is disposed. The lancet can further include a mechanism that can be transitioned between at least two states, wherein in one state (herein referred to as a locked state), the mechanism retains the needle(s) within the lancet in an undeployed position when the lancet is not engaged with the cartridge and in another state (herein referred to as a released state), the mechanism allows the needle(s) to be deployed for puncturing the skin in response to engagement of the lancet with the cartridge. In other words, the engagement of the lancet with the cartridge transitions the mechanism from the locked state to the released state, where in the released state, the mechanism allows the needle(s) to be deployed for puncturing the skin. For example, in some embodiments, the mechanism can include an upper locking portion that can retain an upper spring that is coupled to a needle platform (to which a needle is mounted) in a compressed state, thereby preventing the needle(s) from transitioning into a deployed position. Further, the mechanism can include an upper interference member that prevents the movement of the needle platform when the mechanism is in the locked state. 
     The engagement of the lancet with the cartridge&#39;s housing results in an automatic transition of the mechanism from the locked state to the released state, which transitions the needle(s) into a deployed position in which the needle(s) extends beyond the lancet&#39;s housing and the cartridge housing to puncture the subject&#39;s skin. In some embodiments, the engagement of the lancet with the cartridge causes the upper locking member to release the needle platform, which in turn allows the upper spring to decompress and thus push down the needle platform thereby deploying the needle(s). In some embodiments, the mechanism can further include a lower interference member that restricts the downward movement of the needle platform, when the needle platform is released. In this manner the extent of the penetration of the needle(s) into the skin can be controlled. In certain embodiments, the mechanism can also include a lower locking member that retains a lower spring in a compressed state. The downward movement of the needle platform can cause the release of the lower locking member to allow the lower spring to decompress and exert a force on the needle platform to cause the retraction of the needle(s) into the lancet housing. 
     In this manner, the lancet remains safe before it is engaged with the cartridge as the lancet is not capable of deploying the needle(s) when the lancet is not engaged with the cartridge. Furthermore, in this manner, the lancet remains safe after drawing a physiological sample as the needle(s) automatically retracts back into the lancet&#39;s housing after being deployed. 
     Referring now to  FIG.  1   , a dermal patch system  10  is shown in accordance with an exemplary embodiment. The dermal patch system  10  includes a cartridge  12  that can be affixed to a subject&#39;s skin (e.g., via an adhesive layer disposed on a bottom surface of the cartridge  12 ) and a lancet  100 . As will be discussed in further detail herein, the lancet  100  can be activated to deploy a needle disposed within the lancet  100  to puncture the subject&#39;s skin thereby drawing a physiological sample from the subject. 
     Referring to  FIGS.  2 - 6   , the lancet  100  is shown in accordance with an exemplary embodiment. The lancet  100  includes a housing  102  in which various components of the lancet are disposed and a cap  104  that is coupled to the housing  102 . The lancet  100  can further include an inner sleeve  106  within the housing  102  and a needle frame  108  that is disposed within the inner sleeve  106  and onto which a needle(s)  110  is mounted. While the needle frame  108  is depicted as supporting one needle(s)  110  in other embodiments, the needle frame  108  may support multiple needles  110  (e.g., 2, 3, 4, etc.). The lancet  100  also can include an injection spring  112  and a refraction spring  114  that move a needle of the lancet between various positions. 
     With particular reference to  FIGS.  3 A and  3 B , the housing  102  includes a side wall  116  and a bottom wall  118 . The side wall  116  includes an outer surface  116   a  and an opposed inner surface  116   b . The bottom wall  118  includes an outer surface  118   a  and an opposed inner surface  118   b . The side wall  116  extends vertically from the bottom wall  118 . The side wall  116  has a generally cylindrical shape and the bottom wall  118  is generally circular in shape and is concentric relative to a longitudinal axis of the generally cylindrical side wall and covers a lower opening formed by the generally cylindrical side wall. The inner surface  116   b  of the side wall  116  and the inner surface  118   b  of the bottom wall  118  define an inner volume  120 . 
     The outer surface  116   a  defines a notch  122  that extends circumferentially around the outer surface  116   a  of the side wall  116 . The housing  102  further includes a rim  124  that extends circumferentially around the outer surface  116   a  of the side wall  116 . The inner surface  116   b  defines a first and second column  126  that extend vertically from the inner surface  118   b  of the bottom wall  118 . The columns  126  includes an inner surface  126   a  and a top surface  126   b . The inner surface  126   a  extends vertically between the inner surface  118   b  of the bottom wall  118  and the top surface  126   b . The top surface  126   b  extends longitudinally between the inner surface  116   b  of the side wall  116  and the inner surface  126   a.    
     As will be discussed in further detail herein, before the lancet  100  is inserted into the cartridge  12 , the columns  126  retain the needle(s)  110  of the lancet  100  in an undeployed position. 
     The bottom wall  118  defines an aperture  128  that extends through the bottom wall  118 . Stated another way, the aperture  128  extends between the outer surface  118   a  and the inner surface  118   b  of the bottom wall  118 . As will be discussed in further detail herein, when the lancet is activated via engagement with the cartridge  12 , the needle(s) of the lancet  100  is activated to extend through the aperture  128  and puncture the subject&#39;s skin thereby providing a passageway through which a physiological sample can be drawn from a subject. 
     With particular reference to  FIGS.  4 A and  4 B  the cap  104  includes a top wall  130  with an outer surface  130   a  and an opposed inner surface  130   b . The cap  104  also includes a side wall  132  with an outer surface  132   a  and an opposed inner surface  132   b . The top wall  130  extends longitudinally from and perpendicular to the side wall  132 . The side wall  132  extends vertically from and perpendicular to the top wall  130 . The top wall  130  and the side wall  132  are generally circular in shape and are concentric with one another. The cap  104  also includes an inner cylinder  134  with an outer surface  134   a  and an opposed outer surface  134   b . The inner cylinder  134  extends vertically from and perpendicular to the top wall  130 . The inner cylinder  134  is concentric with the top wall  130  and the side wall  132 . 
     When the cap  104  is coupled to the housing  102  the side wall  132  extends into the inner volume  120  of the housing  102  and at least a portion of the side wall  132  contacts the inner surface  116   b  of the side wall  116  such that the cap  104  couples to the housing  102  via an interference fit. 
     As depicted in  FIG.  5   , the inner sleeve  106  includes a side wall  136  and a bottom wall  138 . The side wall  136  includes an outer surface  136   a  and an opposed inner surface  136   b . The bottom wall  138  includes an outer surface  138   a  and an opposed inner surface  138   b . The side wall  136  extends vertically from the bottom wall  138 . The side wall  136  and the bottom wall  138  are generally circular in shape and are concentric with one another. The inner surface  136   b  of the side wall  136  and the inner surface  138   b  of the bottom wall  138  define an inner volume  140 . The inner surface  136   b  defines a plurality of columns  142  each of which extends vertically from and perpendicular to the inner surface  138   b  of the bottom wall  138 . As will be discussed in further detail herein, when the needle frame  108  is in a deployed position, a portion of the needle frame  108  rests upon the columns  142 . 
     The inner sleeve  106  further includes a plurality of ledges  144  that extend circumferentially about the side wall  136 . Each ledge  144  includes a top surface  144   a , an opposed bottom surface  144   b  and an outer surface  144   c  that extends between the top surface  144   a  and the bottom surface  144   b . The inner sleeve  106  also includes a plurality of locking members  146  that extend from the inner surface  136   b  of the side wall  136 . As will be discussed in further detail herein, the proximal end of the locking members  146  retains the retraction spring  114  in a compressed state in absence of engagement between the lancet  100  and the cartridge  12 . The side wall  136  further defines a plurality of openings  148  that extend through the side wall  136 . Stated another way, the openings  148  extend between the outer surface  136   a  and the inner surface  136   b  of the side wall  136 . Each of the openings  148  is aligned with a proximal end of a locking member  146  to allow the proximal end of a locking member  146  to extend therethrough. 
     The bottom wall  138  defines an aperture  150  that extends through the bottom wall  138 . Stated another way, the aperture  150  extends between the outer surface  138   a  and the inner surface  138   b  of the bottom wall  138 . The aperture  150  is concentric with the aperture  128  of the housing  102 . As will be discussed in further detail herein, when in a deployed position, the needle(s)  110  of the lancet  100  extends through the aperture  150  of the inner sleeve  106  as well as the aperture  128  of the housing  102 . 
     As depicted in  FIG.  6   , the needle frame  108  includes a first cylinder  152  and a second cylinder  154  disposed vertically above the second cylinder  154 . The first cylinder  152  includes a bottom surface  152   a  and an outer surface  152   b . The second cylinder  154  is disposed vertically above the first cylinder  152  and the third cylinder  156  is disposed vertically above the second cylinder  154 . The first cylinder  152  includes a bottom surface  152   a  and an outer surface  152   b  and the second cylinder  154  includes a bottom surface  154   a , an outer surface  154   b  and a top surface  154   c . The third cylinder  156  includes an outer surface  156   a  and a top surface  156   b . Similarly, the protrusion  158  includes an outer surface  158   a  and a top surface  158   b.    
     The bottom surface  152   a  of the first cylinder  152  extends circumferentially about the outer surface  152   b  of the first cylinder. The outer surface  152   b  of the first cylinder  152  extends vertically between the bottom surface  152   a  of the first cylinder  152  and the bottom surface  154   a  of the second cylinder  154 . The bottom surface  154   a  of the second cylinder  154  extends at an angle longitudinally between the outer surface  152   b  of the first cylinder and the outer surface  154   b  of the second cylinder  154 . The outer surface  154   b  extends vertically between the bottom surface  154   a  and the top surface  154   c  of the second cylinder  154 . The top surface  154   c  of the second cylinder  154  extends longitudinally between the outer surface  154   b  of the second cylinder and the outer surface  156   a  of the third cylinder  156 . The outer surface  156   a  extends vertically between the top surface  154   c  of the second cylinder and the top surface  156   b  of the third cylinder. The top surface  156   b  of the third cylinder extends longitudinally between the outer surface  156   a  of the third cylinder  156  and the outer surface  158   a  of the protrusion  158 . The outer surface  158   a  extends vertically between the top surface  156   b  of the third cylinder and the top surface  158   b  of the protrusion  158 . The top surface  158   b  of the protrusion  158  extends across a proximal end of the outer surface  158   a.    
     The injection spring  112  extends vertically between the cap  104  and the needle frame  108 . More specifically, a distal end of the injection spring  112  contacts the inner surface  130   b  of the top wall  130  and a proximal end of the injection spring  112  contacts the top surface  154   c  of the second cylinder  154 . The distal end of the injection spring  112  extends circumferentially around the outer surface  134   a  of the inner cylinder  134 . The proximal end of the injection spring  112  extends circumferentially around the third cylinder  156  and around the protrusion  158 . 
     The needle frame  108  supports the needle(s)  110 . In some embodiments, the needle(S)  110  is molded into the first cylinder  152  or is attached to the bottom surface  152   a  of the first cylinder  152  (e.g., via an adhesive). 
     Referring to  FIG.  7   , the cartridge  12  is shown in accordance with an exemplary embodiment. As will be discussed in further detail herein, the cartridge  12  is formed of a plurality of layers of suitable materials including, but not limited to, polymeric materials (e.g., polyolefins, polyethylene terephthalate (PET), polyurethanes, polynorbornenes, polyethers, polyacrylates, polyamides (Polyether block amide also referred to as Pebax®), polysiloxanes, polyether amides, polyether esters, trans-polyisoprenes, polymethyl methacrylates (PMMA), cross-linked trans-polyoctylenes, cross-linked polyethylenes, cross-linked polyisoprenes, cross-linked polycyclooctenes, inorganic-organic hybrid polymers, co-polymer blends with polyethylene and Kraton®, styrene-butadiene co-polymers, urethane-butadiene co-polymers, polycaprolactone or oligo caprolactone co-polymers, polylactic acid (PLLA) or polylactide (PL/DLA) co-polymers, PLLA-polyglycolic acid (PGA) co-polymers, photocross linkable polymers, etc.). In some embodiments, all or a portion of each material layer may be formed of poly(dimethylsiloxane) (PDMS) to allow visibility of components disposed within the cartridge  12 . While the various layers of material that form the cartridge  12  are said to be layers of polymeric material, it is understood that the layers of material that form the cartridge  12  may be formed of any suitable material (e.g., metal, metal alloy, etc.). As will be discussed in further detail herein, the layers can be stacked and coupled to one another to form the cartridge  12 . In some embodiments, the layers of the cartridge  12  may be formed of aluminum or other suitable metals. In certain embodiments, the layers of the cartridge  12  may be formed of a polymeric coated with aluminum film or another suitable metal film. 
     The cartridge  12  includes an adhesive layer  200 , a bottom layer  300  of polymeric material, a middle layer  400  of polymeric material, a top layer  500  of polymeric material, and a moveable vacuum pin  600  that is disposed between the middle layer  400  and the top layer  500 . The cartridge  12  also includes a protective liner  14  (e.g., formed of paper) that covers the adhesive layer  200 . The protective liner  14  protects the adhesive layer  200  before the cartridge  12  is attached to the skin of a subject. 
     As depicted in  FIG.  8   , the adhesive layer  200  includes a top surface  202  and an opposed bottom surface  204 . The adhesive layer  200  also includes a sample well opening  206  and an air pathway  208  each of which extends through the adhesive layer  200 . That is, the sample well opening  206  and the air pathway  208  extend between the top surface  202  and the bottom surface  204 . 
     The bottom layer  300  ( FIG.  9   ) can have a thickness in a range of about 0.4 mm to about 0.6 mm (e.g., 0.5 mm) and includes a top surface  302  and an opposed bottom surface  304 . The bottom layer  300  also includes a first sample well opening  306  that is connected to a sample channel  308 . The bottom layer  300  further includes a T-shaped vacuum channel  310  that is separate from the first sample well opening  306  and the sample channel  308 . The first sample well opening  306 , the sample channel  308 , and the vacuum channel  310  extend through the bottom layer  300 . That is, the first sample well opening  306 , the sample channel  308 , and the vacuum channel  310  extend between the top surface  302  and the bottom surface  304  of the bottom layer  300 . 
     By way of example, the middle layer  400  ( FIG.  10   ) can have a thickness in a range of about 0.4 mm to about 0.6 mm (e.g., 0.5 mm) and includes a top surface  402  and an opposed bottom surface  404 . The middle layer further includes a sample well opening  406  that is substantially similar in shape and dimension to the first sample well opening  306  of the bottom layer  300 . The middle layer  400  also includes a vacuum aperture  408 , a first vacuum via  410  and a second vacuum via  412 . The first vacuum via  410  and the second vacuum via  412  are substantially similar in shape and dimension. Furthermore, the middle layer  400  includes a first sample via  414  and a second sample via  416  that are substantially similar in shape and dimension. The sample well opening  406 , the vacuum aperture  408 , the first vacuum via  410 , the second vacuum via  412 , the first sample via  414 , and the second sample via  416  extend through the middle layer  400 . That is, the sample well opening  406 , the vacuum aperture  408 , the first vacuum via  410 , the second vacuum via  412 , the first sample via  414 , and the second sample via  416  extend between the top surface  402  and the bottom surface  404  of the middle layer  400 . The sample via  414  and the second sample via  416  may be positioned elsewhere on the middle layer  400  (e.g., closer to a center of the middle layer  400 ). 
     By way of example, the top layer  500  ( FIGS.  11  and  12   ) can have a thickness in a range of about 0.4 mm to about 0.7 mm (e.g., 0.45 mm, 0.5 mm, 0.55 mm, 0.6 mm, 0.65 mm, etc.) and includes a top surface  502  and an opposed bottom surface  504 . The top layer  500  includes a first sample collection pad opening  506  and a second sample collection pad opening  508  that are substantially similar in shape and dimension. The top layer  500  also includes a circular needle aperture  510 . The first sample collection pad opening  506 , the second sample collection pad opening  508 , and the needle aperture  510  extend through the top layer  500 . That is, the first sample collection pad opening  506 , the second sample collection pad opening  508 , and the needle aperture  510  extend between the top surface  502  and the bottom surface  504  of the top layer  500 . The top layer  500  further includes a circular extension  512  that extends vertically from and perpendicular to the top surface  502 . The circular extension  512  is concentric with and extends around the needle aperture  510 . The top layer  500  also includes a first C-shaped extension  514  and a second C-shaped extension  516  both of which extend vertically from and perpendicular to the top surface  502 . The first C-shaped extension  514  and the second C-shaped extension  516  are concentric with and extend partially around the circular extension  512 . Furthermore, the top layer  500  defines a groove  518  and includes a raised surface  520 . As will be discussed in further detail herein, the groove  518  aids in retaining the vacuum pin  600  within the cartridge  12 . 
     With reference to  FIG.  13   , when the cartridge  12  is assembled, the top surface  202  of the adhesive layer  200  is attached to the bottom surface  304  of the bottom layer  300  such that the sample well opening  206  of the adhesive layer  200  aligns with the sample well opening  306  of the bottom layer  300 . Furthermore, when the adhesive layer  200  is attached to the bottom layer  300 , the adhesive layer  200  covers the sample channel  308  and covers a majority of the vacuum channel  310 . The air pathway  208  aligns with a portion of the vacuum channel  310  to provide an air passageway through the adhesive layer  200  and the bottom layer  300 . The air pathway  208  provides airflow and supports the drying of the collection pads before and after collecting the physiological sample. 
     As depicted in  FIG.  14   , when the cartridge  12  is assembled, the top surface  302  of the bottom layer  300  is attached to the bottom surface  404  of the middle layer  400  such that the sample well opening  306  of the bottom layer  300  and the sample well opening  406  of the middle layer  400  align. Together, the sample well opening  306  and the sample well opening  406  form a sample well of the cartridge  12 . In some embodiments, the sample well is configured to retain about 60 μl to about 100 μl. Furthermore, when the bottom layer  300  is attached to the middle layer  400 , the middle layer covers a majority of the sample channel  308  and the vacuum channel  310 . The vacuum aperture  408  aligns with an end of the shaped vacuum channel  310  and the first vacuum via  410  and the second vacuum via  412  align with opposing sides of an end of vacuum channel  310  such that the vacuum aperture  408 , the vacuum via  410  and the second vacuum via  412  provide passage through the middle layer  400  to the vacuum channel  310 . That is, the vacuum aperture  408 , the vacuum via  410  and the second vacuum via  412  are in open communication with the vacuum channel  310 . The first sample via  414  and the second sample via  416  align with opposing ends of the sample channel  308  such that first sample via  414  and the second sample via  416  provide passageway through the middle layer  400  to the sample channel  308 . That is, the first sample via  414  and the second sample via  416  are in open communication with the sample channel  308 . The sample channel  308  and the first sample via  414  form a first sample pathway and the sample channel  308  and the second sample via  416  form a second sample pathway. 
     With reference to  FIGS.  15  and  16   , when the cartridge  12  is assembled, the top surface  402  of the middle layer  400  is attached to the bottom surface  504  of the top layer  500  such that the needle aperture  510  aligns with the sample well opening  406 . That is, the needle aperture  510  aligns with the sample well to provide a passageway through the cartridge  12 . Also, when assembled, the first vacuum via  410  aligns with a corner of the first sample collection pad opening  506  and the second vacuum via  412  aligns with a corner of the second sample collection pad opening  508 . Furthermore, the first sample via  414  aligns with a center of the first sample collection pad opening  506  and the second sample via  416  aligns with a center of the second sample collection pad opening  508 . The first sample collection pad opening  506  provides passageway through the top layer  500  to the first vacuum via  410  and the first sample via  414 . That is, the first sample collection pad opening  506  is in open communication with the first vacuum via  410  and the first sample via  414 . The second sample collection pad opening  508  provides a passageway through the top layer  500  to the second vacuum via  412  and the second sample via  416 . That is, the second sample collection pad opening  508  is in open communication with the second vacuum via  412  and the second sample via  416 . When assembled, the groove  518  of the top layer  500  is disposed vertically above the vacuum aperture  408  such the groove  518  is in open communication with the vacuum aperture  408 . The top surface  402  of the middle layer  400  and the groove  518  of the top layer  500  define a recess (also referred to herein as a “vacuum pin receptacle”) that is shaped and dimensioned to accept at least a portion of the vacuum pin  600 . Furthermore, the raised surface  520  and the top surface  402  define a cavity. In some embodiments, the cavity may be about 800 mm 3  and may retain about 1 g (e.g., 0.5 g-1.5 g) of desiccant (e.g., Silica Gel). 
     When the cartridge  12  is assembled, the vacuum aperture  408  is in open communication with the first vacuum via  410  and the second vacuum via  412  via the vacuum channel  310 . The vacuum channel  310 , the vacuum aperture  408 , and the first vacuum via  410  form a first vacuum pathway and the vacuum channel  310 , the vacuum aperture  408 , and the vacuum channel  310 , the vacuum aperture  408 , and the second vacuum via  412  form a second vacuum pathway. Furthermore, the first vacuum pathway is in communication with the first sample pathway via the first sample collection pad opening  506  and the second vacuum pathway is in communication with the second sample pathway via the second sample collection pad opening  508 . 
     The bottom layer  300 , the middle layer  400 , and the top layer  500  may be affixed to one another by ultrasonic welding, laser welding, or pressure sensitive adhesive. In some embodiments, bottom layer  300 , the middle layer  400 , and the top layer  500  may be formed by die cutting, injection molding, vacuum forming, or pressure molding. 
     In some embodiments, the bottom layer  300 , the middle layer  400 , and the top layer  500  may be formed via die cutting or vacuum forming (or other methods) that result in a large reel or sheet of each layer. These reels may be fed into an indexing machine that presses the layers together for coupling the layers together (e.g., by ultrasonic welding, laser welding, pressure sensitive adhesive, heat bonding, heat sealing, heat-activated bonding, or a combination thereof) thereby assembling the cartridge  12 . 
     The cartridge  12  further includes a first sample collection pad  16  and a second sample collection pad  18 . The first sample collection pad opening  506  is shaped and dimensioned to accommodate the first sample collection pad  16  and the second sample collection pad opening  508  is shaped and dimensioned to accommodate the second sample collection pad  18 . As depicted in  FIGS.  17  and  18   , the first sample collection pad  16  is positioned vertically above, but does not completely cover, the first vacuum via  410  and is positioned vertically above the first sample via  414 . Similarly, the second sample collection pad  18  is positioned vertically above, but does not completely cover, the second vacuum via  412  and is positioned vertically above the second sample via  416 . In some embodiments, the specimen collection pads  16  and  18  may be a CF12 collection pad or cellulose paper. A CF12 collection pad includes a dried blood spot filter paper that can be used as a specimen collection pad. Other types of collection pads may also be employed in various aspects of the present teachings. In other embodiments, the collection pads can be in direct contact with each other. 
     The cartridge  12  also includes a clear adhesive seal  20  that covers the first sample collection pad  16  and the second sample collection pad  18  and allows a user to view the first sample collection pad  16  and the second sample collection pad  18 . The seal  20  is affixed to the top surface  502  of the top layer  500  such that the seal  20  seals the first sample collection pad  16  and the second sample collection pad  18  between the seal  20  and the middle layer  400 . The seal  20  includes a pull tab which allows a user to peel the seal  20  off of the top layer  500  along with the first sample collection pad  16  and the second sample collection pad  18 . The cartridge  12  further includes a foil layer  22  that is affixed to the top of the seal  20 . The foil layer  22  includes two openings that create a viewing aperture for the first and second sample collection pads  16  and  18  respectively. 
     Referring now to  FIG.  20   , the vacuum pin  600  is shown in accordance with an exemplary embodiment. In this embodiment, the vacuum pin  600  includes a handle  602  and a neck  604  that extends from the handle  602 . The vacuum pin  600  also includes a plurality of ridges  606  that extend vertically from the neck  604 . In some embodiments, the ridges  606  may be formed of an elastomeric material. When the vacuum pin  600  is disposed within the vacuum pin receptacle the ridges  606  contact a surface of the vacuum pin receptacle (e.g., a surface of the groove  518 ) thereby providing an airtight seal between the vacuum pin  600  and the vacuum pin receptacle. 
     As depicted in  FIGS.  21 - 23   , the lancet  100  is moveable between a first position (also referred to as an “undeployed position”) ( FIG.  21   ), a second position (also referred to as a “deployed position”) ( FIG.  22   ), and a third position (also referred to as a “retracted position”) ( FIG.  23   ). 
     In the undeployed position (before the lancet  100  is pushed into the cartridge  12 ;  FIG.  21   ) the injection spring  112  and the retraction spring  114  are in a compressed state. In the compressed state, the retraction spring  114  extends vertically between the bottom wall  138  and a proximal end of the locking members  146 . More specifically, a distal end of the retraction spring  114  contacts a lower surface of the proximal end of the locking members  146  and a proximal end of the retraction spring  114  contacts the inner surface  138   b  of the bottom wall  138 . 
     When in the undeployed position the outer surface  144   c  contacts the inner surface  126   a  of the columns  126  which compresses the side wall  136  inwardly. Furthermore, the bottom surface  154   a  of the second cylinder  154  contacts and rests upon the top surfaces  144   a  of the ledges  144  such that the ledges  144  supports the needle frame  108  in the undeployed position. In this position, the injection spring  112  is prevented from decompressing (due to the second cylinder  154  resting upon the ledges  144 ) and the needle(s)  110  is disposed completely within the inner volume  140  of the inner sleeve  106 . 
     When the lancet  100  is inserted into the cartridge  12 , the engagement of the lancet with the cartridge  12  causes the lancet  100  to automatically move from the undeployed position to the deployed position. 
     When the lancet  100  is pushed into the cartridge  12  ( FIGS.  24 - 26   ), the circular extension  512  extends through the aperture  128  to contact the bottom wall  138 . Specifically, a top surface of the circular extension  512  contacts the outer surface  138   a  of the bottom wall  138  which forces the inner sleeve  106  to move vertically upward in the direction of arrow A ( FIG.  22   ) within the housing  102 . This vertical movement causes the ledges  144  to extend vertically above the top surfaces  126   b  of the columns  126 . Moving beyond the top surfaces  126   b  of the columns  126  allows the side wall  136  to decompress and expand in the direction of arrow B ( FIG.  22   ) and extend toward the inner surface  116   b  of the side wall  116 . In this position, the bottom surface  144   b  of the ledges  144  rest upon the top surfaces  126   b  of the columns  126  and the outer surfaces  144   c  of the ledges  144  contacts the inner surface  116   b  of the side wall  116 . 
     The expansion of the side wall  136  causes the inner volume  140  of the inner sleeve  106  to have a larger width relative to when the inner sleeve  106  is in the undeployed position such that at least a portion of the side wall  136  has a larger width than the second cylinder  154  (the widest portion of the needle frame  108  which allows the needle frame  108  move vertically downward in the direction of arrow C) ( FIG.  22   ). 
     Furthermore, the injection spring  112  also causes the needle frame  108  to move in the direction of arrow C as the ledges  144  no longer prevent the injection spring  112  from expanding. The force applied by the injection spring  112  causes the needle frame  108  (and therefore the needle(s)  110 ) to travel with a force that is sufficient to cause the needle(s)  110  to puncture the skin of a subject wearing the cartridge  12 . Stated another way, the injection spring  112  causes the needle(s)  110  to extend through the aperture  150  of the inner sleeve  106 , through the aperture  128  of the housing  102 , and through the needle aperture  510  and the sample well of the cartridge  12  to puncture the skin of a subject. In the deployed position, the bottom surface  154   a  of the second cylinder  154  rests upon the columns  142  and at least a portion of the outer surface  154   b  of the second cylinder  154  contacts the inner surface  136   b  of the side wall  136 . 
     While moving in the direction of arrow C, the outer surface  152   b  contacts the locking members  146  which causes a proximal portion of locking members  146  that is aligned with an opening  148  to extend into the opening. In this position, the locking members  146  no longer contact the retraction spring  114  thereby allowing the retraction spring  114  to decompress and expand. When decompressed, the retraction spring  114  contacts the outer surface  152   b  of the first cylinder  152  which causes needle frame  108  to also move in the direction of arrow D ( FIG.  12   ). That is, after moving to the deployed position, the retraction spring  114  causes the needle(s)  110  to retract back into the inner volume  140  of the inner sleeve  106  via the apertures  128  and  150  of the lancet  100 . After penetrating the skin of a subject, the retraction spring  114  causes the needle(s)  110  to automatically retract back into the housing of the lancet  100  thereby placing the lancet  100  in the retraced position. 
     As previously discussed herein, the lancet includes a mechanism that can transition the lancet between a locked state and a released state. In various embodiments, this mechanism includes the columns  126 , the ledges  144 , and the locking members  146 . An upper locking portion of the mechanism refers to the columns  126  and the ledges  144  while a lower locking portion refers to the locking members  146  as the columns  126  and the ledges  144  can be positioned vertically above the locking members  146 . The term upper interference portion refers to the top surface  144   a  of the ledges  144  as this surface interferes with the needle frame&#39;s  108  ability to transition to the deployed position when the mechanism is in the locked state. As used herein, a lower interference member refers to the columns  142  as the columns  142  interfere with the needle frame&#39;s  108  ability to further extend beyond a desired position. 
     In use, after affixing the cartridge  12  to the skin of the subject, a user of the dermal patch system  10  pushes the lancet into the cartridge  12  which causes the needle(s)  110  to move to the deployed position and puncture the subject&#39;s skin and draw a physiological sample. After the needle(s)  110  retracts into the lancet  100 , the drawn physiological sample pools within the physiological sample well of the cartridge  12 . 
     When the physiological sample is within the physiological sample well, a user can pull the vacuum pin  600  in the direction of arrow E ( FIG.  26   ) to move the vacuum pin  600  from a first position (also referred to as an “undeployed” position) ( FIGS.  24  and  25   ) to a second position ( FIG.  26   ) (also referred to as an “deployed” position). Moving the vacuum pin  600  to the deployed position creates a vacuum within the first vacuum pathway, the second vacuum pathway, the second sample pathway, and the second vacuum pathway. The strength of the vacuum is proportional to the amount the vacuum pin  600  moves. That is, the more the vacuum pin  600  moves, the stronger the vacuum. This vacuum causes the drawn physiological sample to travel to the first collection pad  16  and the second collection pad  18  via the first and second sample pathway respectively ( FIGS.  17  and  18   ). In some embodiments, capillary flow, wicking and gravity assist the vacuum pin  600  in drawing the physiological sample towards the collection pads  16  and  18 . The first collection pad  16  and the second collection pad  18  absorb the drawn physiological sample. The user can determine the collection pads  16  and  18  have absorbed the physiological sample by viewing the collection pads  16  and  18  through the transparent adhesive seal  20 . 
     After the collection pads  16  and  18  have absorbed the physiological sample, the user can remove the cartridge  12  from the subject&#39;s skin. The user can then send the cartridge  12  to a laboratory where a medical professional can remove the collection pads  16  and  18  by pulling the pull tab of the seal  20 . Once removed, the medical professional can apply various solutions to the collection pads  16  and  18  which mixes with the physiological sample to form a processed physiological sample that has been freed from the collection pads  16  and  18 . 
     With reference to  FIG.  27   , in some embodiments wherein the cartridge  12  includes the QR code  26 , a user of a computer system  28  may scan the QR code  26  to determine a test to perform on the stored physiological sample and/or to view and/or update an EMR  30  that is associated with the QR code  26 . In these embodiments, the EMR  30  is stored in an EMR database  32  that is in communication with the computer system  28 . Furthermore, the QR code  26  may be employed to preserve the chain of custody of the dermal patch system  10 . 
     In these embodiments, the computer system  28  may include an application that provides access to the EMR database  32  via a network connection and allows a user to photograph of scan the QR code  26 . As shown in  FIG.  27   , the EMR database  32  includes a plurality of EMRs  30  each of which is associated with an individual subject. The application causes the computer system  28  to scan or retrieve an image of the QR code  26 , analyze the QR code  26  and associate the QR code  26  with an EMR  30 . In some embodiments, the computer system  28  may then update the associated EMR  30  to indicate a physiological sample has been obtained from the subject. The computer system  28  may automatically update the EMR  30  automatically or based on a user input. In some embodiments, after associating an EMR  30  with the QR code  26 , the computer system  28  may analyze information within the EMR  30  to determine a test to be performed on the obtained physiological sample and may prompt a user of the computer system to perform the test. 
     Referring now to  FIG.  28   , a computer system  700  is shown in accordance with an exemplary embodiment. The computer system  700  may serve as any computer system disclosed herein (e.g., the computer system  28 ). As used herein a computer system (or device) is any system/device capable of receiving, processing, and/or sending data. Computer systems include, but are not limited to, microprocessor-based systems, personal computers, servers, hand-held computing devices, tablets, smartphones, multiprocessor-based systems, mainframe computer systems, virtual reality (“VR”) headsets and the like. 
     As shown in  FIG.  28   , the computer system  700  includes one or more processors or processing units  702 , a system memory  704 , and a bus  706  that couples the various components of the computer system  700  including the system memory  704  to the processor  702 . The system memory  704  includes a computer readable storage medium  708  and volatile memory  710  (e.g., Random Access Memory, cache, etc.). As used herein, a computer readable storage medium includes any media that is capable of storing computer readable; program instructions and is accessible by a processor. The computer readable storage medium  708  includes non-volatile and non-transitory storage media (e.g., flash memory, read only memory (ROM), hard disk drives, etc.). Computer program instructions as described herein include program modules (e.g., routines, programs, objects, components, logic, data structures, etc.) that are executable by a processor. Furthermore, computer readable program instructions, when executed by a processor, can direct a computer system to function in a particular manner such that a computer readable storage medium comprises an article of manufacture. Specifically, the computer readable program instructions when executed by a processor can create a means for carrying out at least a portion of the steps of the methods disclosed herein. 
     The bus  706  may be one or more of any type of bus structure capable of transmitting data between components of the computer system  700  (e.g., a memory bus, a memory controller, a peripheral bus, an accelerated graphics port, etc.). 
     The computer system  700  may further include a communication adapter  712  which allows the computer system  700  to communicate with one or more other computer systems/devices via one or more communication protocols (e.g., Wi-Fi, BTLE, etc.) and in some embodiments may allow the computer system  700  to communicate with one or more other computer systems/devices over one or more networks (e.g., a local area network (LAN), a wide area network (WAN), a public network (the Internet), etc.). 
     In some embodiments, the computer system  700  may be connected to one or more external devices  714  and a display  716 . As used herein, an external device includes any device that allows a user to interact with a computer system (e.g., mouse, keyboard, touch screen, etc.). An external device  714  and the display  716  may be in communication with the processor  702  and the system memory  704  via an Input/Output (I/O) interface  718 . 
     The display  716  may display a graphical user interface (GUI) that may include a plurality of selectable icons and/or editable fields. A user may use an external device  714  (e.g., a mouse) to select one or more icons and/or edit one or more editable fields. Selecting an icon and/or editing a field may cause the processor  702  to execute computer readable program instructions stored in the computer readable storage medium  708 . In one example, a user may use an external device  714  to interact with the computer system  700  and cause the processor  702  to execute computer readable program instructions relating to at least a portion of the steps of the methods disclosed herein. 
     Referring now to  FIG.  29   , a cloud computing environment  800  is depicted in accordance with an exemplary embodiment. The cloud computing environment  800  is connected to one or more user computer systems  802  and provides access to shared computer resources (e.g., storage, memory, applications, virtual machines, etc.) to the user computer systems  802 . As depicted in  FIG.  29   , the cloud computing environment includes one or more interconnected nodes  804 . Each node  804  may be a computer system or device local processing and storage capabilities. The nodes  804  may be grouped and in communication with one another via one or more networks. This allows the cloud computing environment  800  to offer software services to the one or more computer services to the one or more user computer systems  802  and as such, a user computer system  802  does not need to maintain resources locally. 
     In one embodiment, a node  804  includes computer readable program instructions for carrying out various steps of various methods disclosed herein. In these embodiments, a user of a user computer system  802  that is connected to the cloud computing environment may cause a node  804  to execute the computer readable program instructions to carry out various steps of various methods disclosed herein. 
     Referring now to  FIG.  30   , a method for obtaining a physiological sample from a subject is shown in accordance with an exemplary embodiment. 
     At  902  a user (e.g., a medical professional, a subject, etc.) removes the protective liner  14  from the cartridge  12  to expose the adhesive layer  200  and applies the cartridge  12  to the skin of the subject via the adhesive layer  200  at a suitable location (e.g., on a leg, arm, etc.) as previously discussed herein. 
     At  904 , the user pushes the lancet  100  into the cartridge  12  to draw a physiological sample (e.g., a blood sample, a sample of interstitial fluid, etc.) from the subject as previously discussed herein. 
     At  906 , the user pulls the vacuum pin  600  to draw the physiological sample to the specimen collection pads  16  and  18  as previously discussed herein. 
     At  908 , the user removes the cartridge  12  from the skin of the subject as previously discussed herein. 
     At  910 , the user sends the specimen collection pads  16  and  18  to a laboratory for further analysis by a medical professional. In some embodiments, the user first removes the specimen collection pads  16  and  18  from the cartridge  12  by pulling the pull tab of the seal  20 . In other embodiments, the user sends the cartridge  12  with the specimen collection pads  16  and  18  to the medical professional. In these embodiments, the cartridge  12  may include a desiccant which dries the specimen collection pads  16  and  18 . 
     At  912 , a user of the computer system  28  scans the QR code  26  and updates an EMR  30  to indicate a physiological sample was collected from the subject as previously discussed herein. 
     As previously discussed, some of the steps of the various methods disclosed herein may be implemented by way of computer readable instructions, encoded or embedded on computer readable storage medium (which excludes transitory medium), which, when executed by a processor(s), cause the processor(s) to carry out various steps of the methods of the present disclosure. 
     While various embodiments have been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; embodiments of the present disclosure are not limited to the disclosed embodiments. Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing embodiments of the present disclosure, from a study of the drawings, the disclosure, and the appended claims. 
     In the claims, the word “comprising” does not exclude other elements or steps, and the indefinite article “a” or “an” does not exclude a plurality. A single processor or other processing unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measured cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.